US20050015048A1 - Infusion treatment agents, catheters, filter devices, and occlusion devices, and use thereof - Google Patents

Abstract

Embodiments include an infusion-occlusion system having a delivery catheter, a guide catheter adapted to receive the delivery catheter, and a guidewire with an occlusion device adapted to be received within the guide catheter. The guide catheter of the catheter kit may be provided with an occlusion device at the distal end of the guide catheter. The delivery catheter may have an accessory lumen, coaxial and/or co-linear lumen, a supporting mandrel, and/or an occlusion device at its distal end. Moreover, according to embodiments, occlusion devices may be a single material or a composite balloon having an inner liner and an outer layer of different materials, a high compliance low pressure balloon, and/or a filter device that restricts particles from passing through but does not restrict fluid, such as blood. An inflation device with a large volume and low volume syringe can be used to inflate the balloon.

Description

• This application is a Continuation-in-Part of co-pending application Ser. No. 60/467,402, filed May 1, 2003, entitled “Multiple Occlusion Device”; and is a Continuation-in-Part of co-pending application Ser. No. 10/387,048, filed Mar. 12, 2003, entitled “Multiple Occlusion Device”; and claims the priority benefit thereof.
FIELD
• Cardiovascular catheters and occlusion devices.
BACKGROUND
• It is increasingly important that a physician or surgeon delivering substances, such as a treatment agent or drug, is able to efficiently and accurately locate the desired target tissue for effective delivery of the substance. This is particularly true when the concentration of the substance required at the target site cannot be safely or effectively achieved by introduction of the substance to a location remote from the target site. Moreover, the physician may only want to treat the diseased portion of an organ or tissue and avoid treating the healthy portions.
• Such localized treatment is desired not only for substance delivery but is necessary for other treatments, such as myocardial revascularization. Myocardial revascularization is a procedure in which “holes” are formed in ischemic ventricular tissue to increase blood flow to the treated area. It is thought that the tissue damage (e.g., holes) encourages growth of blood vessels in the treated area. Thus, similar to substance delivery, myocardial revascularization is a procedure that is preferably performed only on specific areas that require treatment.
• For example, to achieve localized treatment of tissue, such as tissue in a heart, physicians and surgeons can use catheters and occlusion devices. Specifically, cardiovascular guide catheters are generally percutaneous devices used to advance through a vasculature of a patient to a region of interest and are devices through which another catheter or device may be inserted. Delivery catheters are generally catheters used to deliver a treatment agent to a region of interest in a vasculature of a patient and typically may be inserted through another catheter (e.g., a guide catheter). Moreover, occlusion devices, such as balloons, may be attached to a delivery catheter to occlude a region of interest in a vasculature. Guidewires are generally devices used to guide through a vasculature of a patient to a region of interest and typically may be inserted through another catheter (e.g., an introducer).
SUMMARY
• In one embodiment, there is disclosed an infusion-occlusion system for infusing a treatment agent to a region of interest of an artery or vein (including a blood vessel of the human heart) that includes a delivery catheter, a guide catheter adapted to receive the delivery catheter, a pressure increasing device adapted to be connected to the delivery catheter, a pressure-sensing device adapted to be connected to the delivery catheter, an inflation device adapted to be connected to the delivery catheter, and a guidewire with an occlusion device adapted to be received within the guide catheter. In another embodiment, the guide catheter of the catheter kit is provided with an occlusion device at the distal end of the guide catheter. In another embodiment, the delivery catheter of the catheter kit is provided with an occlusion device at the distal end of the delivery catheter.
• Examples of occlusion devices include balloons of a material and dimension to have an outer diameter that inflated to selected diameters when the balloon is inflated with a selected inflation pressure and/or volume of gas or fluid. The balloon may be inflated by an inflation device having a high volume, low pressure syringe for initially inflating the balloon to a controlled low pressure initial diameter and having a low volume syringe for further inflating the balloon with a controlled volume increment(s) to produce controlled diameter increase(s) up the an occlusion diameter. Moreover, an occlusion device may be a composite balloon having an inner liner and an outer layer of different materials, a high compliance low pressure balloon, and/or a filter device that restricts particles from passing through but does not restrict fluid, such as blood. Also, according to embodiments, occlusion devices may include various types of balloons, such as a high compliance low pressure balloons having a thermoplastic blend copolymer material with a polyether block amide resin moiety and/or a polyetheramide moiety. Likewise, according to embodiments, occlusion devices may include various types of high-compliance low-tension balloons, such as a composite or multi-layer expanded PolyTetraFlouroEthylene (ePTFE) balloon having an inner liner.
• For instance, according to embodiments, a catheter, such as a guide catheter, may include a coronary sinus access guide with a collection cage or filter device, to filter unwanted particles or material from blood. Also, a delivery catheter may be a catheter that has a support mandrel extending therethrough and/or may have lumen or tubes in a coaxial or co-linear orientation with the longitudinal axis of the catheter.
• In another embodiment, there is disclosed a method of providing treatment in a vessel of a patient that includes placing a guide catheter in the vessel of the patient, feeding a delivery catheter through the guide catheter, where the delivery catheter is provided with an occlusion device at its distal end, feeding at least one guidewire with an occlusion device through the guide catheter and/or the delivery catheter, deploying the occlusion device(s) of the guidewire(s), deploying the occlusion device at the delivery end of the delivery catheter, administering a treatment agent through the delivery catheter, disengaging all the occlusion devices, and removing the guidewire(s), the delivery catheter, and the guide catheter from the vessel of the patient. In another embodiment, the method further provides for aspirating the vessel of the patient prior to disengaging all of the occlusion devices. Also described is are methods including occluding a blood vessel, infusing treatment agent, such as progenitor cells (such as progenitor cells derived from bone marrow), to treat a region of interest of the blood vessel for a first time period, then allowing blood and/or treatment agent perfusion or flow to the region of interest for a second period of time, and repeating infusing and perfusion as necessary to accomplish sufficient treatment.
• Specific examples of apparatus to allow for blood and/or treatment agent perfusion or flow to the region of interest include occlusion balloons that can be deflated and inflated to selected outer diameter, catheters having perfusion lumen that bypass and exit holes in the catheter on either end of the occlusion device, and catheters having guidewire lumen with exit holes through the catheter proximal to the occlusion device and an exit port at the distal end of the catheter. Additional features, embodiments, and benefits will be evident in view of the figures and detailed description presented herein.
BRIEF DESCRIPTION OF THE DRAWINGS
• The embodiments of the invention are illustrated by way of example and not by way of limitation in the figures of the accompanying drawings in which like references indicate similar elements. It should be noted that references to “an” embodiment of the invention in this disclosure are not necessarily to the same embodiment, and they mean at least one.
• FIG. 1 schematically illustrates a cross-section of the heart showing blood flow throughout the heart.
• FIG. 2 schematically illustrates a vertical cross-section of the heart.
• FIG. 3A illustrates a catheter system having a guide catheter, delivery catheter, guide wires, and multiple occlusion devices.
• FIG. 3B shows a sectional side view ofFIG. 3A through line C—C′ ofFIG. 3A.
• FIG. 4 schematically illustrates the placement of the catheters ofFIGS. 3A and 3B in the coronary sinus.
• FIG. 5 schematically illustrates a guide catheter.
• FIG. 6 shows a sectional view ofFIG. 5 through line C—C′ ofFIG. 5.
• FIG. 7 is a side view of a cannula and a filter device in a sheath.
• FIG. 8 is a view ofFIG. 7 from perspective “A”.
• FIG. 9 is a side view of a distal end of a cannula including a filter device having a distal portion with a second diameter that is approximately the inner diameter of a blood vessel at a region of interest.
• FIG. 10 is a view ofFIG. 9 from perspective “B”.
• FIG. 11 is a side section view of a filter device with a distal portion having a first diameter and balloons coupled to the filter device and/or the cannula.
• FIG. 12 is a side-section view of a filter device with a distal portion having a second diameter, wherein the filter device is attached to inflated balloons which are attached to a cannula.
• FIG. 13 is a side section view of a filter device with a distal portion having a third diameter, where the filter device is attached to deflated balloons which are attached to a cannula.
• FIG. 14 is a side sectional view of a filter device having a distal portion attached to tendons which pivot at pivot point and extend through a cannula.
• FIG. 15 is a side section view of a filter device with a distal portion having a second diameter, wherein the filter device is attached to tendons which extend through a cannula.
• FIG. 16 is a side section view of a filter device with a distal portion having a third diameter and tendons attached to the distal portion and extending through a cannula.
• FIG. 17 is a front cross sectional view of the filter device ofFIG. 9 showing a proximal portion of the filter device axially attached to an exterior surface of a cannula and lumens extending through the cannula.
• FIG. 18 is a front cross sectional view of a filter device having a proximal portion axially attached to an exterior surface of a cannula, wherein the filter device has a helical spring shape.
• FIG. 19 is a flow diagram of a process for using a filter device to restrain and aspirate particles.
• FIG. 20 illustrates a guide catheter with an occlusion device.
• FIG. 21 illustrates a telescoping guide catheter system.
• FIG. 22 illustrates a balloon catheter tip with a guidewire.
• FIG. 23 illustrates a balloon catheter tip proximal end.
• FIG. 24 shows a section view ofFIG. 23 through Line D-D′.
• FIG. 25 schematically illustrates a delivery catheter system.
• FIG. 26 schematically illustrates a side elevational view of a delivery catheter.
• FIG. 27 schematically illustrates a side view of the distal portion of the delivery catheter ofFIG. 26.
• FIG. 28 schematically illustrates transverse cross-sections of the delivery catheter ofFIG. 26 taken along the line9-9.
• FIG. 29 schematically illustrates transverse cross-sections of the delivery catheter ofFIG. 26 taken along the line9-9.
• FIG. 30 schematically illustrates a catheter system.
• FIG. 31 schematically illustrates a sectional view of a catheter with a self inflating balloon.
• FIG. 32 schematically illustrates the placement of a catheter in the coronary sinus.
• FIG. 33 schematically illustrates the diaphragmatic surface of the heart.
• FIG. 34 schematically illustrates the sternocostal surface of the heart.
• FIG. 35 schematically illustrates a partial cross-sectional perspective view of a catheter within the coronary sinus.
• FIG. 36 illustrates a tapered balloon catheter tip.
• FIG. 37 illustrates a balloon catheter tip with a guidewire.
• FIG. 38 illustrates a balloon catheter tip with a guidewire.
• FIG. 39 schematically illustrates a catheter within a vein.
• FIG. 40 illustrates a guidewire tip with an occlusion device.
• FIG. 41 illustrates a guidewire with an occlusion device.
• FIG. 42 illustrates the guidewire ofFIG. 41 with the occlusion device open.
• FIG. 42B, is a front view ofFIG. 42A from perspective “A”.
• FIG. 42C, is a side of the occlusion device ofFIG. 42A showing the occlusion device overlapping leaflets.
• FIG. 43 illustrates a guidewire with an occlusion device.
• FIG. 44 is a cross-sectional view of a cannula and a balloon.
• FIG. 45 is a cross-section view of a cannula and a lined ePTFE balloon.
• FIG. 46 is a flow diagram of a process for forming a lined ePTFE balloon.
• FIG. 47 is an elevated cut-away view of layers of ePTFE windings.
• FIG. 48 is a cross section view of a cannula and a balloon.
• FIG. 49A is a cross sectional view of a cannula and a balloon inflated to occlude a blood vessel.
• FIG. 49B may be a cross sectional view ofFIG. 49A from perspective “A”, according to an embodiment.
• FIG. 50 is a cross sectional view of a cannula and a postinflated deflated balloon.
• FIG. 51 is a cross sectional view ofFIG. 48 from perspective “A”.
• FIG. 52 is a cross sectional view ofFIG. 49A from perspective
• FIG. 53 is a cross sectional view ofFIG. 50 from perspective
• FIG. 54 is a flow diagram of a process for using a balloon to occlude a blood vessel or vein.
• FIG. 55 illustrates a balloon outside diameter growth rate.
• FIG. 56 illustrates a graph of blood vessel pressure over time.
• FIG. 57 illustrates a cross-sectional view of a centrifugal pump.
• FIG. 58 schematically illustrates a pressure increasing device.
• FIG. 59 schematically illustrates a pressure increasing device.
• FIG. 60 schematically illustrates a pressure transferring device.
• FIG. 61 schematically illustrates a pressure-maintaining or dampening device.
• FIG. 62 schematically illustrates a pressure-maintaining or dampening device with inlet and outlet.
• FIG. 63 is a flow diagram of a method of treating a patient, in accordance with an embodiment.
• FIG. 64A is a cross sectional view of a cannula and a balloon.
• FIG. 64B is a cross-sectional view the apparatus ofFIG. 64A from perspective “A”.
• FIG. 65A shows the balloon and cannula ofFIG. 64A, with the balloon inflated to a second inflation volume.
• FIG. 65B is a cross-sectional view the apparatus ofFIG. 65A from perspective “A”.
• FIG. 66A shows the cannula and balloon ofFIG. 65A, with the balloon inflated to a third inflation volume.
• FIG. 66B is a cross-sectional view the apparatus ofFIG. 66A from perspective “A”.
• FIG. 67A shows the cannula and balloon ofFIG. 66A, with the balloon inflated to a selected fourth inflation volume.
• FIG. 67B is a cross-sectional view the apparatus ofFIG. 67A from perspective “A”.
• FIG. 68 is a graph showing the relationship between the outer diameter of a balloon and the volume of inflation contrast fluid injected into the balloon.
• FIG. 69A is a side perspective view of a cannula having a balloon attached to its distal end and an infusion lumen and accessory lumen running through the cannula.
• FIG. 69B is a cross section view of the first section ofFIG. 69A from perspective “A”.
• FIG. 69C is a cross sectional view of the second section ofFIG. 69A from perspective “B”.
• FIG. 69D is a cross sectional view of the balloon section ofFIG. 69A from perspective “C”.
• FIG. 69E is a cross sectional view of the third section ofFIG. 69A from perspective “D”.
• FIG. 69F is a cross section view of the fourth section ofFIG. 69A from perspective “E”.
• FIG. 70 is a cross sectional view of the balloon section ofFIG. 69A from perspective “C”, with the balloon inflated to a second volume that is less than that shown inFIG. 69D.
• FIG. 71A is a cross-sectional view of a cannula and a balloon, where the cannula includes coaxially aligned lumens.
• FIG. 71B is a cross-sectional view of the apparatus ofFIG. 71A from perspective “A”.
• FIG. 72A is a cross-sectional view of a cannula and a balloon, where the cannula includes coaxially and co-linearly aligned lumens.
• FIG. 72B is a cross-sectional view of the apparatus ofFIG. 72A from perspective “B”.
• FIG. 73 is a cross-sectional view of a cannula and a balloon, where the cannula has coaxially and co-linearly aligned lumens.
• FIG. 74 is a cross-sectional view of the apparatus ofFIG. 71A from perspective “C” prior to forming tack joints between the guidwire tube and the infusion tube.
• FIG. 74B is the structure ofFIG. 74A after forming tack joints between the guidwire tube and the infusion tube.
• FIG. 75A is a cross sectional view of an apparatus to inflate a low volume balloon to occlude a blood vessel.
• FIG. 75B is a cross-sectional view of the apparatus ofFIG. 75A from perspective “A”.
• FIG. 76 shows the latch mechanisms ofFIG. 75A in an unlatched position.
• FIG. 77 shows the latch mechanisms ofFIG. 76 relatched.
• FIG. 78 showsFIG. 77 after the inflation volume adjustment knob has been rotated or turned to retain fluid.
• FIG. 79 showsFIG. 78 after the inflation volume adjustment knob has been rotated or turned to inflate the balloon with a selected inflation volume fluid.
• FIG. 80 showsFIG. 79 after unlatching inner the plunger lock to deflate the balloon.
• FIG. 81 shows an alternate embodiment of an apparatus to perform the functions ofFIG. 75A-80.
• FIG. 82 is a flow diagram of a process for treating a region of interest of a blood vessel with one or more treatment agents and/or progenitor cells.
• FIG. 83 is a cross-sectional view of an occlusion balloon attached to a cannula having holes through an exterior surface of the cannula proximate to the balloon, where the holes extend to a lumen in the cannula having an exit distal to the balloon.
• FIG. 84 is a cross-sectional view ofFIG. 83 from perspective “A”.
• FIG. 85 is a cross-sectional view of the apparatus shown inFIG. 83 advanced to a region of interest of a blood vessel.
• FIG. 86 is a cross-sectional view of a cannula having a balloon attached to its distal end and a bypass lumen extending from a hole distal to the balloon to a hole proximal to the balloon.
• FIG. 87 shows the apparatus ofFIG. 86 where the infusion lumen extends to a location distal toballoon8810.
• FIG. 88 is a cross-sectional view of a cannula having a balloon attached to its distal end, and infusion lumen to provide treatment agent to a location distal to the balloon, and a bypass lumen to allow for perfusion of liquid from the location distal to the balloon to the location proximal to the balloon.
• FIG. 89 is a cross-sectional view of a cannula having two balloons attached to its distal end, and infusion lumen exiting the cannula between the balloons, and a bypass lumen to allow perfusion between a location proximal to both balloons and a location distal to both balloons.
DETAILED DESCRIPTION
• Referring first toFIG. 1, a simplistic cross-sectional view of a heart is shown to illustrate blood flow throughout the heart. Deoxygenated blood returning from the body comes intoheart100 from eithersuperior vena cava126 orinferior vena cava116 and collects inright atrium122.Right atrium122 contracts to pump the blood throughtricuspid valve118 where it flows intoright ventricle114.Right ventricle114 contracts to send the blood throughpulmonary valve120 intopulmonary artery124 where it goes into the lungs (not shown). The oxygenated blood returning from the lungs flows throughpulmonary veins102 where it flows intoleft atrium101.Left atrium101 contracts sending the blood through bicuspid ormitral valve104 and intoleft ventricle108. Whenleft ventricle108 contracts, the blood is sent throughaortic valve106 and intoaorta128.Left ventricle108 andright ventricle114 are separated byventricular septum110.
• Referring toFIG. 2, a more detailed vertical cross-section ofheart100 is shown. Blood first collects inright atrium122 fromsuperior vena cava126 or other veins.Right atrium122 also includesright auricle142. Whenright atrium122 contracts, blood is sent throughtricuspid valve118 and intoright ventricle114.Tricuspid valve118 is made up of three cusps:posterior cusp176,septal cusp178, and anterior cusp180 (shown retracted).Right ventricle114 has a number of muscles that contract to send blood out ofright ventricle114. Some of the muscles inright ventricle114 include right anterior papillary muscle174 (shown cut), and right posteriorpapillary muscle172. Other parts of the anatomy ofright ventricle114 includesconus arteriosis156, supraventricular crest152, andmoderator band160 andseptal band162 of septalmarginal trabacula164. The blood outflow to the pulmonary trunk is marked byarrow154. Pulmonary trunk is shown as138. The blood returning from the lungs returns by leftpulmonary veins134 and rightpulmonary veins136 where it collects inleft atrium101.Left atrium101 also includesleft auricle138. When leftatrium101 contracts, blood is sent throughmitral valve104 which is made up of posterior cusp132 andanterior cusp130. Blood flows throughmitral valve104 and intoleft ventricle108. Muscles in the left ventricle include left posteriorpapillary muscle170, left anteriorpapillary muscle168.Septum110 separates leftventricle108 fromright ventricle114.Septum110 includes the muscular part ofintraventricular septum186, interventricular part of the membranous septum182, and the atrial ventricular part ofmembranous septum184. Whenleft ventricle108 contracts, blood is sent throughaortic valve106 which includes leftsemi-lunar cusp146, posterior semi-lunar (non-coronary)cusp148, and rightsemi-lunar cusp150. Most of the blood flows throughaortic valve106 and into ascendingaorta128, although some of the blood is diverted into the openings of coronary arteries140.
• Referring now toFIG. 3A, a catheter system having a guide catheter, a delivery catheter, guidewires and multiple occlusion system is illustrated. In one embodiment,system300 includesguide catheter302 havingproximal portion305 anddistal portion306.System300 includesguide catheter302 havinglumen304, for allowingsystem300 to be fed and maneuvered over a guidewire, such asguidewire320 and/orguidewire330. In one embodiment,lumen304 extends the length ofguide catheter302 fromproximal portion305 todistal portion306. Representatively, in a procedure, a guidewire, such asguidewire320 and/or330 may be initially placed through a region of interest in a physiological lumen (e.g., a blood vessel) and guidecatheter302 is advanced on/over the guidewire to or through a region of interest in an over the wire (OTW) fashion. In another embodiment,system300 may be a rapid transfer type catheter assembly and only a portion of system300 (e.g., a distal portion) is advanced over the guidewire (also seeFIG. 37). It is appreciated that a guidewire, such asguidewire320 and/orguidewire330 may be retracted or removed oncesystem300 is placed at a region of interest.
• System300 includesguide catheter302 havinglumen304 therethrough.Guide catheter302 includesdistal portion306 havingocclusion balloon308 aboutdistal portion306.Delivery catheter310 is shown disposed throughlumen304 ofguide catheter302.Delivery catheter310 hasdistal end312.Balloon314 is provided atdistal end312.Notch316 is located atdistal end312 andguidewire opening318 intolumen313 ofdelivery catheter310 is provided distallyadjacent notch316.Guidewire320 is disposed throughnotch316 andlumen313 withindelivery catheter310 and outguidewire opening318 ofdelivery catheter310.Guidewire320 includesdistal end322 andocclusion device324.Occlusion device324 may be an occlusion balloon as described herein attached to the exterior surface ofguidewire320 at or adjacentdistal end322 by adhesive, heat bonding, laser bonding, and/or shrink wrap bonding, such is as described herein. Also shown disposed throughguide catheter lumen304 isguidewire330.Guidewire330 includesdistal end332 andocclusion device334. Also note thatocclusion device334 may be an occlusion balloon as described herein attached to the exterior surface ofguidewire330 at or adjacentdistal end332 by adhesive, heat bonding, laser bonding, and/or shrink wrap bonding, such is as described herein. In this embodiment, guidwire330 is shown disposed through guide catheter302 (e.g., from a proximal end to a distal end of the guide catheter) but is not engaged bydelivery catheter310.
• Proximal portion305 ofsystem300 may reside outside the body of a patient while the remainder ofsystem300 is percutaneously introduced into, for example, the vascular system of a patient via a blood vessel. As shown inFIG. 3A,proximal portion305 ofsystem300 includeshub351.Hub351 includesguidewire320, guidewire330, and treatmentagent delivery lumen319. In one embodiment, relative to the materials for the various cannulas described herein, a housing ofhub351 is a hard or rigid polymer material, e.g., a polycarbonate or acrylonitrile bubadiene styrene (ABS). A distal end ofhub351 has an opening to accommodate a proximal end ofguide catheter302.Hub351 also hasguidewire track391,guidewire track392, and a number of cavities at least partially through hub351 (extending in a distal to proximal direction) to accommodateguidewire320, guidewire330, and treatmentagent delivery lumen319. In accordance with embodiments, treatmentagent delivery lumen319 may be used to infuse a treatment agent including a liquid, a drug, infusion pellets, suspended cells, stem cells, microspheres, a peptide, a growth factor, and/or various other appropriate liquids, materials, and therapeutic agents (mixed or not mixed with blood) to be delivered locally and/or to a region of interest in a blood vessel, as described herein. Also, a treatment agent may include performing an infusate-uptake-enhancing procedure such as of electroporation, ultrasonic excitation, and/or photodynamic therapy. A proximal portion ofhub351 flares to separate a spacing betweenguidewire320 and guidewire330, and treatment agent delivery lumen319 (i.e., a distal end ofhub351 has width W1 sufficient to accommodate a proximal end ofguide catheter302 and a proximal end ofhub351 has width W2 that is greater than width W1).Hub351 also includesmedial section390 which may have various appropriate lengths such as between a fraction of an inch and 10 inches to allowhub351 to function appropriately. Moreover, guidecatheter302,delivery catheter310, and/orhub351 may include additional lumen, tubes, cannula, as described herein, such as to inflate or expand occlusion devices, balloons, and/or to provide pressure measurements and/or relief.
• For example, in one embodiment,hub351 may have at least the following functions: guidewire movement and control, guide catheter movement and control, delivery catheter movement and control, occlusion device expansion and retraction, balloon inflation and deflation, treatment agent delivery, and aspiration of fluid and/or particles from a region of interest of a blood vessel. With reference toFIG. 3A, in this embodiment,hub351 also includesstrain relief370 catheter holder373 (e.g., such as for holding a delivery catheter disposed through lumen304), treatmentagent delivery port323,guidewire port398, andguidewire port399. A proximal end ofguide catheter302 terminates insidehub351 near a distal end ofhub351.Guidewire320, guidewire330, and treatmentagent delivery lumen319 extend proximally beyond a proximal end ofguide catheter302 and may be secured in respective cavities throughhub351.
• FIG. 3A also shows a distal portion ofhub351 includingstrained relief370.Strained relief370 may be an elastic tubular component that may act to reduce stress and inhibit shaft (e.g., of guide catheter302) kinking for/or during the transition, movement, and/or control of a guidewire, such asguidewire320 and/orguidewire330, a catheter, such asguide catheter302 and/ordelivery catheter320, and/or other functions identified above forhub351.
• FIG. 3B shows a sectional side view ofFIG. 3A through line C—C′ ofFIG. 3A.FIG. 3B showsguidewire320 and guidewire330 disposed withinlumen304 ofguide catheter302.FIG. 3B also showsdelivery catheter310 disposed throughguide catheter302, wherein treatmentagent delivery lumen319 is disposed withindelivery catheter310.
• According to embodiments, the components ofsystem300, such asguide catheter302,delivery catheter310,balloon308,balloon314,occlusion devices324 and334,hub351,strained relief370,catheter holder373,medial section390, and other cannula and/or tubes surrounding lumens may be made of a material including materials described herein for such components, as well as materials described herein for balloons. For example, the components ofsystem300 may include a polycarbonate or acrylonitrile bubadiene styrene (ABS); a biocompatible polymer such as a polyether block amide resin; a biocompatible polymer blend of polyurethane and silicone a polymer having a structure of a regular linear chain of rigid polyamide segments interspaced with flexible polyether segments, a styrenic block copolymer (SBC), or a blend of SBC's; a thermoplastic blend copolymer material having one of a polyether block amide resin moiety and a polyetheramide moiety; a styrene isoprene styrene (SIS), a styrene butadiene styrene (SBS), a styrene ethylene butylene styrene (SEBS), a polyetherurethane, an ethyl propylene, a ethylene vinyl acetate (EVA), an ethylene methacrylic acid, an ethylene methyl acrylate, and an ethylene methyl acrylate acrylic acid; a material from a material family of one of styrenic block copolymers and polyurethanes; a nylon material; a melt processible polymer; and/or a low durometer material. It is also contemplated that other components of system, apparatus, or devices described herein, such as other catheters, cannulas, balloons, filter devices, occlusion devices, tubes (e.g., such aslumen989, lumen surrounding material, lumen sleeves, lumen cannula and/or lumen tubes, such as described below with respect toinfusion lumen9520 and/oraccessory lumen9530 of FIGS.69A-F), syringes, pressure increasing devices, pressure transfer devices, pressure maintaining devices, and/or pumps described below made of a material including materials described above.
• In use,system300 may be refered to as a “rapid transfer type system” designed to have the distal end ofguide catheter302 advanced percutaneously to a desired first location in a blood vessel whereballoon308 may be inflated to occlude the blood vessel and/or to fix the distal end ofguide catheter302 at the first location. Note thatballoon308 may be inflated later on in the use ofsystem300, such as afterdelivery catheter310 is advanced as described below. Next, guidewire320 may be advanced percutaneously to a desired second location in the same or a different blood vessel so that thedistal end312 ofdelivery catheter310 can be advanced or tracked overguidewire320 by feeding lumen lumen131 overguidewire320. This “over the wire” (OTW) is also known as monorail. Then,balloon314 may be inflated to occlude the blood vessel and/or to fix the distal end ofdelivery catheter310 at or adjacent to the second location. It is also contemplated thatguidewire330 may be advanced through a blood vessel and to a third location and thatocclusion devices324 and/or334 may be expanded to occlude blood vessels, such as at one or more locations to define a distal end of a region of interest or treatment area to be treated by a treatment agent infused into the blood vessel from treatmentagent delivery lumen319 of delivery lumen310 (e.g., where the region of interst, treatment agent, and infusion of treatment agent from the delivery catheter are in accordance with corresponding descriptions herein).
• For instance, in one example, guidecatheter302 may be fed and maneuvered as described above into blood vessels of a person's heart. More particularly,FIG. 4 schematically illustrates the placement of the catheters ofFIGS. 3A and 3B in the coronary sinus, such ascoronary sinus3286 ofFIGS. 32-33. As shown inFIG. 4,delivery catheter310 may be fed throughlumen304 ofguide catheter302 and into middlecardiac vein406, such as by being fed throughlumen304 afterguide catheter302 is placed through a region of interest in an OTW fashion, or beforeguide catheter302 is placed through a region of interest in a rapid transfer type fashion.Guidewire320 may also be fed throughguide catheter302 through guidewire opening318 ofdelivery catheter310 and into middlecardiac vein406 distal todistal end312 ofdelivery catheter310.Guidewire330 may be fed throughlumen304 and into smallcardiac vein492. Next,occlusion device324,occlusion device334, andballoon314 may be engaged to occlude smallcardiac vein492, and respectively occlude a portion of middlecardiac vein406 betweenballoon314 andocclusion device334. Next,balloon308 may be engaged. A treatment agent may be fed through treatmentagent delivery cannula319 distal to balloon314 and proximal toocclusion device324.Occlusion device334 is engaged, andballoon308 is engaged to prevent the treatment agent from reaching the right atrium through shunts and/or anastimoses. Following the conclusion of the administration of the treatment agent,occlusion device324,occlusion device334, andballoon314 may be disengaged, and guidewire320,delivery catheter310, and guidewire330 are removed fromlumen304 ofguide catheter302. Then,coronary sinus486 may be aspirated (e.g., seehole988 ofFIG. 9 and accompanying text) and then balloon308 disengaged and guidecatheter302 removed from coronary sinus.
• Embodiments also includesystem300 having a filter device instead ofballoon308. For instance, the system and process described above forFIGS. 3A, 3B and4 may also apply to a system and process havingfilter device720, instead of and at the location ofballoon308, to restrain and aspirate particles shown and described below forFIGS. 7-19.
• Referring now toFIG. 5, a guide catheter is illustrated.FIG. 5 shows guidecatheter502 which may or may not be or be part ofsystem300, such as ifguide catheter502 is part ofguide catheter302, as shown and described with respect toFIG. 3. In particular,guide catheter502 has proximal end504 anddistal end506, which may be or be part ofproximal end305 and/ordistal end306, as shown and described with respect toFIG. 3.Lumen508 is shown inFIG. 5 extending throughguide catheter502 fromguide catheter opening514 at proximal end504 todistal end506.Guide catheter502 also hasballoon510 attached around the exterior surface ofcatheter502 at or adjacentdistal end506.Lumen508 and/orballoon510 may correspond tolumen304 and/orballoon308, as shown and described with respect toFIG. 3.FIG. 5 also includesballoon inflation cannula512 withinguide catheter502 from proximal end504 to opening513 withinballoon510.
• FIG. 6 shows a sectional view ofFIG. 5 through line C—C′ ofFIG. 6. As shown inFIG. 6,balloon inflation cannula512 is disposed withinguide catheter502 such as by being fed through or disposed throughguide catheter opening514 and extended into a portion ofballoon510, such as to provideopening513 to inflateballoon510.
• In one embodiment, proximal end504 includesguide catheter opening514 andballoon inflation cannula512. Also provided isvalve device516, withselector mechanism518.Guide catheter502 may have an opening extending from 1umen508 atdistal end506 to guidecatheter opening514 at proximal end504. Thus, in embodiments implementingvalve device516,selector mechanism518 may be disengaged to allow the opening extending fromlumen508 to guidecatheter opening514 to remain open. Alternativelyselector mechanism518 may be engaged, such as by turning, to causevalve device516 to close the opening betweenlumen508 and guidecatheter opening514 atvalve device516 and instead direct any fluid flowing through the opening and towardguide catheter opening514 throughnozzle520 and out ofvalve device516, such as into collectingreservoir524 which may or may not be attached tonozzle520 such as by a hose over and fastened by friction or a clamp tonozzle520. Thus,selector mechanism518 may be engaged, for example, to aspirate fluid such as blood and/or particles such as described herein (e.g., seehole988 ofFIG. 9 and accompanying text), form a region of interest of a blood vessel throughlumen508, and out ofnozzle520. This could be used, for example, to aspirate a vessel distal to balloon510, prior to deflatingballoon510 so that fluid will be removed from the vessel.
• According to embodiments, guidecatheter502 may be an appropriate length for reaching a region of interest of a subject during a medical procedure, such as by having a length of between three inches and five feet. Also, guidecatheter502,balloon510, andballoon inflation cannula512 may be formed of materials similar to those for forming components ofsystem300 as described above. Moreover,balloon inflation cannula512 may include one or more of a synthetic or natural latex or rubber, such as a polymer material; a polyetheramide; a plasticiser free thermoplastic elastomer; a thermoplastic blend; a block copolymer of polyether and polyester (e.g., such as a polyester sold under the trademark Hytrel® of DUPONT COMPANY); a biocompatible polymer such as a polyether block amide resin (e.g., for instance, PEBAX® of ATOCHEM CORPORATION); a polycarbonate or acrylonitrile bubadiene styrene (ABS); a biocompatible polymer such as a polyether block amide resin; a styrene isoprene styrene (SIS), a styrene butadiene styrene (SBS), a styrene ethylene butylene styrene (SEBS), a polyetherurethane, an ethyl propylene, an ethylene vinyl acetate (EVA), an ethylene methacrylic acid, an ethylene methyl acrylate, an ethylene methyl acrylate acrylic acid, a material from a material family of one of styrenic block copolymers and polyurethanes, a melt processible polymer, a low durometer material, and nylon. Likewise,balloon510 may be attached to guidecatheter502 by processes described herein for attaching a balloon to a catheter, including by laser, adhesive, shrink tube bonding, and heat bonding.
• In another embodiment, proximal end504 ofguide catheter502 is provided withflap519 instead ofvalve device516.Flap519 is, for example, a material similar to a material for inflation cannula512 (e.g., such as materials described above with respect to components ofsystem300, and/or a synthetic or natural latex or rubber, and/or other materials that can block fluid flow).Flap519 has a suitable dimensions to block off and occludelumen508, such as to prohibit blood and/or treatment agent from flowing byflap519. Thus,flap519 serves to seal offguide catheter opening514 when there are no devices disposed in or throughguide catheter opening514 such as a device orcannula holding flap519 open. For instance,flap519 may be attached to the inside ofcatheter502 alonglumen508, at one or more locations, by one or more of a hinge, a pin, an anchor, laser bonding, adhesive bonding, and heat bonding. Thus, when the device, catheter, or cannula (not shown) is inserted intoguide catheter opening514, the device or cannula pushesflap519 opens with some degree of force, such as by forcingflap519 from close position CL to open position OP, as shown inFIGS. 5 and 6. For instance, a device, catheter, or cannula inserted intoguide catheter opening514 indirection583 can pushflap519 from close position CL to open position OP, as shown inFIGS. 5 and 6, and allowlumen508 to define an opening extending fromguide catheter opening514 todistal opening594. After the device, cannula or cannula is removed fromguide catheter opening514 and/or pushingflap519 open,flap519 has a property that causesflap519 to resist or occlude a flow of any liquid or particles flowing fromlumen508 towardsguide catheter opening514. Hence, after the device, cannula or cannula is removed from pushingflap519 open,flap519 has a property and/or is mounted to close, such as by causingflap519 to move from open position OP to close position CL, and to be biased in closed position CL with sufficient forrce to stop or occlude a flow of any liquid or particles flowing fromlumen508 towardsguide catheter opening514 Thus, when closed,flap519 prevents fluid originating from opening594 from flowing throughlumen508 withinguide catheter502 and flowing out guidecatheter opening514.
• In another embodiment, proximal end504 ofguide catheter502 includes sealingcap530 adapted to seal offguide catheter opening514 instead ofvalve device516 orflap519.Sealing cap530 serves to seal offguide catheter opening514 such as by having threads that engage threads at the proximal end ofguide catheter502, or by having a recess for engaging a lip at the proximal end ofguide catheter502. Thus sealingcap530 may be used to seal off proximal end ofguide catheter502 when attached thereto, and may be removed from proximal end ofguide catheter502 such as to aspirate a region of interest of a vessel as described above with respect tovalve device516. More particularly,cap530 may be attached to guidecatheter502 until such time as it is desired to aspirate a vessel distal to balloon510 (e.g., such as after the balloon is inflated and prior to deflating the balloon). At that time,cap530 can be removed, and liquid from the vessel can flow fromlumen508 throughguide catheter502 outguide catheter opening514 and intocollection receptacle532.
• Furthermore, according to embodiments, catheters described herein, such as a guide catheter, include a filter device capable of restricting certain particles from passing therethrough but not restricting the flow of fluid, such as blood. For instance, a coronary sinus access guide or catheter may have a collection cage or filter device to filter unwanted particles or material from blood. For example,FIG. 7 is a side view of a cannula and a filter device in a sheath. As shown inFIG. 7,apparatus700 includescannula710, such as a cannula having a dimension suitable for percutaneous advancement through a blood vessel, includesproximal section712 anddistal end714.FIG. 7 also showsfilter device720 havingproximal portion722 axially coupled or connected to an exterior surface ofcannula710 at or adjacentdistal end714. For instance, an inner diameter ofproximal portion722 may be attached to an exterior surface ofcannula710 by laser bonding, adhesive bonding, heat bonding, or other bonding techniques described herein at an appropriate location adjacent todistal end714 to filter unwanted particles or material from blood flowing indirection784 in a treatment region, such as region ofinterest996 as described below.
• Filter device720 also hasdistal portion724 having a first diameter D1 under a first set of conditions. For example, a first set of conditions may includefilter device720 being restrained (e.g., to, for example, less than an inner diameter of a blood vessel into which it will be placed) bysheath790, or restricted by a retraction or contraction pressure, such as a pressure resulting from a deflated balloon, tendon, or self contracting filter device.
• Thus, as shown inFIG. 7, diameter D1 is smaller than and restrained by diameter of the sheath DS, and is larger than diameter of the cannula DC, forming first angle A1 between generally conical shapedinner surface737 and the surface ofcannula710. For example, according to embodiments, first angle A1 shown inFIG. 7 may be an angle between 0° and 20°, such as an angle of 2°, 3°, 4°, 5°, 6°, or 10°. As a resultdistal portion724 may have first diameter in a range between 1 mm and 14 mm, such as by having an outer diameter corresponding to French size5F,6F,7F,8F,9F,10F,12F,15F,18F,24F, and30F.
• FIG. 8 is a view ofFIG. 7 from perspective “A”.FIG. 8 shows conical shapeinner surface737 atfilter device720 includingproximal portion722 having a diameter approximately equal to diameter of cannula DC anddistal portion724 having first diameter D1.FIG. 8 also showssheath790 having diameter of sheath DS, such as a diameter of sheath sufficient to restrict or contain the diameter ofdistal portion724 to first diameter D1. Note that although inFIGS. 7 and 8,cannula710,proximal portion722,distal portion724, andsheath790 are shown having side sections through line A-A′ that are approximately circular, various other closed shapes are contemplated such as an oval, a square, a triangle, a trapezoid, an ellipse, or a combination thereof.
• Moreover,sheath790 may be retracted in a proximal direction (e.g., direction784) so thatsheath end794 is pulled back beyonddistal portion724 allowing first diameter D1 to expand beyond a diameter of the sheath DS. Similarly, according to embodiments, pull wire792 (e.g., such as a wire disposed withinsheath790 extending fromdistal end714 to a proximate end ofsheath790 external to the body of a subject) may be pulled or removed, such as by being pulled indirection784, to form a seam in sheath790 (e.g., such as wherepull wire792 was prior to removal) so thatsheath790 may be entirely or partially removed from encasingcannula710 and/orfilter device720. More particularly,filter device720 may have a property such that first diameter D1 ofdistal portion724 can be transformed, enlarged, or expanded to a different second diameter under a second set of conditions. Consequently, first diameter D1 can be transformed to become a second diameter, such as in response toexpansion pressures730 and732 applied to generally conical shapedinner surface737.
• In one embodiment,distal portion724 has a different second diameter under a second set of conditions, where the second diameter approximates an inner diameter of a blood vessel. For example,FIG. 9 is a side view of a distal end of a cannula including a filter device having a distal portion with a second diameter that is approximately the inner diameter of a blood vessel at a region of interest. Specifically,FIG. 9 shows cannula710 percutaneously advanced throughblood vessel990, andsheath790 retracted so thatsheath end794 is retracted beyondproximal portion722 allowingfilter device720 to expand indirections786 and788 so thatdistal portion724 has different second diameter D2 under the second set of conditions (e.g., retraction of sheath790) that is at least equivalent to inner diameter of blood vessel DV at region ofinterest996.
• Note that region ofinterest996 may be a region of interest proximate to wheredistal portion724contacts blood vessel990, and optionally including the region contained inblood vessel990 distal to filterdevice720 and containingdistal end714. For example, second diameter D2 may be a diameter approximately equal to the diameter of a blood vessel at a region or point of interest, a diameter slightly less than that of a blood vessel at a point or region of interest, or a diameter slightly greater than that of a diameter of a blood vessel at a point or region of interest. More particularly, second diameter D2 may be greater than the diameter ofblood vessel990 at a point or region of interest, such as by being in a range of between 0% and 25% larger, such as by being 3% larger, 5% larger, 10% larger, or 15% larger in diameter.
• Specifically,filter device720 may have a property such that first diameter D1 can be transformed to become second diameter D2 in response to expansion pressures having a total of between approximately two atmospheres in pressure and six atmospheres in pressure applied to generally conical shaped inner surface737 (e.g., such as caused bypressures730 and732) to causesurface737 to expand to second generally conical shapedinner surface937. According to embodiments,expansion pressures730 and732 may be the result of, applied by, or caused by, a fluid flow indirection784. For example,expansion pressures730 and732 may be applied by a blood flow ofblood986 indirection784 having a pressure greater than 2.0 millimeters of Mercury (mmHg) in pressure to causedistal portion724 to expand indirections786 and788.
• Also, according to embodiments,filter device720 may include self-expanding materials (e.g., such as shape memory alloys, including for example, Nickel-Titanium) or other materials that have shape memory where the memorized shape is the expanded shape. To modify the shape (e.g., to restrict the shape) a sheath may be placed overfilter device720. Removing the restriction will allow the shape memory material to return to its memorized shape (e.g., an expanded shape). Specifically, for example,filter device720 may include a self-expanding frame portion to provide the second set of conditions under whichdistal portion724 has second diameter D2.
• Furthermore, according to embodiments,filter device720 may have a property, such as by including a material, such that under the second condition (e.g., the condition described above wherein second diameter D2 approximates an inner diameter of a blood vessel)filter device720 will restrain from flowing throughfilter device720 plurality ofparticles980 having a particle size greater than an average particle size ofblood cells982. More specifically, for example, as shown inFIG. 9,filter device720 may restrain particles980 (e.g., such as infusion pellets, suspended cells, stem cells, and/or microspheres) influid986 flowing indirection784, from flowing throughfilter device720. Thus, particles having a particle size approximately that of an average particle size of blood cells, such asblood cells982, contained influid986 flowing indirection784, may travel throughfilter device720 without being restrained (e.g., such as if unrestrained blood cell983 originated in region of interest996). For example, a typical red blood cell has a size of approximately 7 micrometers in diameter, and a typical white blood cell has a size of between approximately 7 and 15 micrometers in diameter.
• Consequently, according to embodiments,filter device720 may include a material, such asmaterial930 having or pierced by plurality of openings, such asopenings931 and932 having a dimension suitable to allow a fluid, such as blood, to pass therethrough. More particularly,openings931 and932 may have a dimension suitable to allow a fluid includingblood cells982 to flow therethrough, and having a dimension suitable to restrainparticles980 having a particle size greater than an average particle size of blood cells. For example,openings931 and932 may have a diameter of between 10 micrometers and 100 micrometers in diameter. Thus,openings931 and932 may act like a trap, a sieve, and/or a strainer of particles to restrainparticles980. Moreover, according to embodiments, particles, materials, and matter restrained byfilter device720 may be restrained such as by causing the particles, material, or matter to bond to or be coupled to filterdevice720, to rest againstfilter device720, or to be restrained within the area ofblood vessel990 distal to filterdevice720, such as the area includingdistal end714. It is contemplated thatmaterial930 may include various suitable materials such as natural or synthetic material, plastic, stainless steel, PEBAX 91 (a biocompatible polymer such as a polyether block amide resin, sold under the trademark PEBAX® of ATOCHEM CORPORATION, PUTEAUX, FRANCE), embolic protection material, and/or various other appropriate filtration materials.
• Material930 may be connected or attached to a frame portion, such as by laser bonding, adhesive bonding, thermal bonding, mechanical restriction (e.g., such as ifmaterial930 is woven or sewn through structure or portions of the frame, such as structure having space between pieced of the structure or holes in the frame), and or various other appropriate attachment methods as described herein.
• For example,filter device720 may include a frame portion defined byproximal portion722 anddistal portion724. According to embodiments, an inner diameter of the frame portion may be attached to an outer surface ofcannula710, atproximal portion722 such as by laser bonding, adhesive bonding, thermal, bonding, mechanical bonding (e.g., such as is described above for attachingmaterial930 to the frame portion), and/or various other techniques of bonding sufficient to preclude all or a portion of the inner diameter offilter device720 from becoming separated from the outer surface ofcannula710. For example, a sufficient attachment would preclude a portion or all of an inner diameter offilter device720 from becoming detached from the outer surface ofcannula710 during expansion or retraction ofdistal portion724, a first set of conditions, a second set of conditions, during restriction of a fluid flowing throughfilter device720, or during aspiration of particles from region ofinterest996, such as is described herein (e.g., seehole988 ofFIG. 9 and accompanying text).
• It is contemplated that the frame portion may include one or more of a leaflet shaped support, a helical shaped support, a cone shaped support, a spar shaped support, a basket shaped support, a ring shaped support (e.g., to allowmaterial930 to form a “parachute” shape), and/or a combination thereof. More specifically, a frame portion may have a plurality of extending supports extending fromproximal portion722 todistal portion724, such as a spar, a rod, a shaft, a dowel, a pull, a spine; and a plurality of cross supports disposed between the plurality of extending supports, such as a rib, a cross link, and a cross wrap wrapped around, over, or under the extending support. In addition, it is contemplated thatfilter device720 and/or the frame portion offilter device720 may include one or more of tubing, wires, ribs, ribbons, forged materials, extruded materials, cast materials, and deposited materials. For example,FIG. 9 showsfilter device720 having longitudinally disposed circumferentially spaced elements, includingelements920,921, and922. Moreover,filter device720 may include ribs or cross supports, such asribs924 and926.
• Likewise,filter device720 may include a material stretched on a frame portion to form a generally conical shaped inner surface. For example,FIG. 10 is a view ofFIG. 9 from perspective B.FIG. 10 showsproximal portion722 having diameter of proximal portion DP andmaterial930 stretched to form generally conical shapedinner surface937 betweenproximal portion722 anddistal portion724 having second diameter D2. Thus,frame portion720 may havematerial930 on, over and/or under longitudinally disposed elements or spars spaced and defining a conical shape extending fromproximal portion722 todistal portion724, such as is shown byconical shape937 ofFIGS. 9 and 10 and/orconical shape737 shown inFIGS. 7 and 8.FIG. 10 also showsblood vessel990 having diameter of vessel DV which is slightly less than second diameter D2. Thus, in one embodiment, it is contemplated that second diameter D2 approximates an inner diameter of a coronary sinus of a subject at a region of interest, such as by having a diameter of between 6.5 millimeters and 11 millimeters. Also,material930 may be stretched on a frame portion, such as aframe including elements920,921, and922 and/orribs924 and926 to form generally conical shapedinner surface737 under a first set of conditions and generally conical shapedinner surface937 under a different second set of conditions.
• In addition,FIG. 9 shows generally conical shapedinner surface937 forming second angle A2 between generally conical shapedinner surface937 and the surface ofcannula710. According to embodiments, second angle A2 may be an angle between 5° and 85°, such as an angle of 10°, 20°, 25°, 30°, 35°, 40°, 45°, 50°, 55°, 60°, and 65°. Consequently,distal portion724 may have second diameter D2 in a range between three mm and 15 mm, such as, an outer diameter corresponding to French size9F,12F,15F,18F,24F,28F,30F,32F, and34F.
• Furthermore, according to embodiments,distal portion724 may have various cross sectional aspects or shape. Specifically, althoughdistal portion724 is shown inFIGS. 7 and 9 having a “W” shaped profile,distal portion724 may have various appropriate shaped profiles, such as a “M” shape, a flat shape, a “C” shape, a “S” shape, and/or a shape including one or more of the previously mentioned shapes. Likewise,elements920,921, and922, as well asribs924 and926 may also have various appropriate shapes, such as those described above with respect todistal portion724. Also, it is contemplated that a self-expanding or self-contracting frame as described herein may include frame structure, portions, elements, or ribs having a metallurgy with a memory, an elastic material, nitinol (NiTi), a shaped memory alloy (e.g., such as a memory alloy that when formed to a shape remembers or returns to that shape if not restrained or damaged). For example, a self-expanding or self-extracting frame may be a metal frame with a helical spring shape, or a shape including ribs with a memory, that flexes when constrained.
• Once particles are restrained, such as is described above with respect to filterdevice720 restraining particles, material, and matter, according to embodiments,filter device720 may include a property to allow aspiration of the particles, material, and matter being restrained. Specifically,cannula710 may include one or more holes, such ashole988 through the exterior surface ofcannula710, as shown inFIG. 9, to allow aspiration of restrained particles, such asparticle980. Thus,hole988 may be used to aspirate or draw unwanted material, such as infusion pellets, suspended cells, stem cells, and/or microspheres out of the treatment zone or region of interest, such as via evacuation or suction to pull the unwanted material throughhole988 and intocannula710. For example, aspiration of restrained particles is contemplated to include aspiration offluid986, andblood cells982, such as via a suction or vacuum provided athole988 provided via acannula including lumen989 extending fromhole988 throughcannula710 toproximal section712. According to embodiments lumen989 may include a surrounding material, sleeve, cannula or lumen, such as described below with respect toinfusion lumen9520 and/oraccessory lumen9530 of FIGS.69A-F. Hole988 may be located between 0.2 mm and 10 mm cm from the end ofdistal end714.
• Distal portion724 may be expanded from first diameter D1 (FIGS. 7 & 8) to second diameter D2 (FIGS. 9 & 10) as a result offilter device720 being self expanding, expansion pressure from fluid flow indirection784, and/or various other appropriate systems or devices, such as for applyingpressures730 and732. For example,FIG. 11 is a side section view of a filter device with a distal portion having a first diameter and balloons attached to the filter device and/or the cannula.FIG. 11shows balloons1132 and1134 attached to filterdevice720 atattachment locations1139, and attached tocannula710, such as ata attachment locations1129, such that inflation ofballoons1132 and1134 (e.g., such as inflation via cannulas as described below inFIGS. 17 and 18) transformsdistal portion724 offilter device720 from first diameter D1 to a second diameter. According to embodiments, the balloons may be attached to the filter device and/or cannula at attachments locations1129 and/or1139, such as by an adhesive, heat bonding, laser bonding, welding, or stitching.
• Thus, for example, balloons1132 and1134 may be inflated with sufficient pressure to cause an expansion pressure as described with respect toFIGS. 7 and 9 (e.g., such as pressure similar to those described above forpressure730 and732) applied to generally conical shaped inner surface1137 (e.g., such as similar toconical shape737 described above).
• Consequently, balloons1132 and1134 may be inflated to have a volume greater than that shown inFIG. 11 to transformdistal portion724 from first diameter D10 to a larger second diameter. For example,FIG. 12 is a side-section view of a filter device with a distal portion having a second diameter, wherein the filter device is attached to inflated balloons which are attached to a cannula.FIG. 12 shows inflatedballoons1142 and1144 attached to filterdevice720 and cannula710 (e.g., such as described above with respect toballoons1130 and1131) for transformingdistal portion724 offilter device720 from first diameter D10 to second diameter D20. For instance, in one embodiment,inflated balloons1142 and1144 may beballoons1132 and1134 respectively, after inflation to becomeballoons1142 and1144. Note that according to embodiments, diameter D10 may be a diameter similar to those described above with respect to first diameter D1, and second diameter D20 may be a diameter similar to those described above with respect to second diameter D2.
• Also, according to embodiments,filter device720 may include anchors proximate todistal portion724 for engaging tissue, to anchorfilter device720, and/orcannula710 to an inner diameter of a blood vessel. For instance,FIG. 11 shows a filter device with a distal portion having anchors capable of engaging tissue of a blood vessel. As shown inFIG. 11, anchors1122 and1124 proximate todistal portion724, whereanchors1122 and1124 include a protruding barb capable of engaging tissue of a blood vessel, such as by piercing the inner diameter tissue to a sufficient depth to engage a sufficient amount of the tissue ofblood vessel990 to prohibit and anchor from being removed from its engagement ofblood vessel990, such as by the flow of liquid or blood indirection784 towardfilter device720 as described herein. Moreover, anchors1122 and1124 may be attached to elements or ribs of a frame offilter device720 such aselement922 andrib926 ofFIG. 9. Thus, anchors1122 and1124 may be extended indirections786 and788 as shown inFIG. 11, to engage tissue of blood vessel as shown inFIG. 12. Consequently, anchors1122 and1124 may be disengaged from tissue ofblood vessel990 such as by retraction ofdistal end724 and/or by movingfilter device720 indirection985. Hence, anchors1122 and1124 may be disengaged from tissue, such as by retracting or contractingdistal portion724 to moveanchors1122 and1124 indirections1186 and1188 as shown inFIG. 12.
• For instance,filter device720 may have a property such that second diameter1120 can be transformed to become or constrict to approximately first diameter D10 in response to a retraction or contraction pressure such as shown bypressures1140 and1141 ofFIG. 12. According to embodiments, sufficient retraction pressure may be in the range of between approximately two atmospheres in pressure and 35 atmospheres in pressure applied to generally conical shapedinner surface1138. More particularly, as shown inFIG. 12,balloons1142 and1144 attached to filterdevice720 andcannula710 may be deflated (e.g., such as via lumens as described below with respect toFIGS. 17 and 18) to transformdistal portion724 offilter device720 from second diameter D20 approximately to first diameter D10. For example,FIG. 13 is a side section view of a filter device with a distal portion having a third diameter, where the filter device is attached to deflated balloons which are attached to a cannula.FIG. 13 shows deflatedballoons1152 and1154 attached to filter device720 (e.g., as described above with respect to attachment at attachment locations1139) and attached to cannula710 (e.g., such as described above with respect to attachment at attachment locations1129) such thatdistal portion724 is transformed to third diameter D30. For instance, in one embodiment, deflatedballoons1152 and1154 may beballoons1132 and1134 respectively, after inflation and deflation (e.g., such as after inflation ofballoons1132 and1134 to becomeballoons1142 and1144, and deflation ofballoons1142 and1144 to becomeballoons1152 and1154).
• Therefore, for example,inflated balloons1142 and1144 may be deflated to causepressures1140 and1141 sufficient to create a retraction pressure as described above, applied to generally conical shapedinner surface1138, thereby retractingdistal portion724 todirections1186 and1188 from second diameter1120 to third diameter D30 as shown inFIG. 13, which may be a diameter in a range ofbetweeen 100 percent and 130 percent of D10.
• FIG. 14 is a side view of a distal portion of a cannula including a filter device having a distal portion attached to tendons which pivot at a pivot point and extend through a cannula. As shown inFIG. 14,filter device720 includestendons1430 and1440 which extend fromproximal section712 ofcannula710 to pivotpoints1432 and1442 and then are attached todistal portion724, such as via attachment atattachment locations1439. Note that attachment atattachment locations1439 may be an attachment achieved such as is described with respect to attachment atattachment locations1139 and1129.Tendons1430 and1440 may extend fromproximal section712 ofcannula710 to pivotpoints1432 and1442, such as via lumens as described below inFIGS. 17 and 18. Thus,tendons1430 and440 may be actuated such as by releasing tension or extending the tendons indirection985 to transformdistal portion724 from first diameter D11 to a second diameter (e.g., such as a result of an expansion pressure similar to those described above with respect toFIGS. 7-13 andpressures730 and732 applied to generally conical inner surface1437). It is contemplated that generally conicalinner surface1437 may be similar toconical shape737 as described above. It is also to be appreciated thattendons1430 and1440 may extend throughproximal section712 such as to exit a proximal portion ofcannula710 exterior to the body of a subject so thattendons1430 and1440 may be locked in a locking position. More particularly,tendons1430 and1440 may extend through a tendon port similar toport398 above (seeFIG. 3 and accompanying text) and be locked in a locking position, such as by a locking mechanism disposed within a proximal portion ofcannula710, a tendon port, or external to the tendon port. Hence,tendons1430 and1440 may be retained in their locking position until it is desired to actuate them as described above. Moreover, after actuation oftendons1430 and1440 as described above, the tendons may be manipulated, or retracted as described below and returned to a locking position, such as their original locking position prior to actuation.
• Moreover,tendons1430 and1440 may be of various suitable materials such as natural or synthetic fiber, plastic, stainless steel and/or various other appropriate metals. Likewise,pivot points1432 and1442 may be hard points such as a point where the tendon exitscannula710 or a lumen as described below with respect toFIGS. 17 and 18. Moreoverpivot point1432 and1442 may contain various appropriate pivot structures such as a curved surface, a hard point, an exit hole of an inflation lumen, an exit of a lumen such as lumens described below inFIGS. 17 and 18, and/or an aspiration hole such as hole988 (seeFIG. 9 and accompanying text), and/or a small wheel.
• For example,FIG. 15 is a side section view of a filter device with a distal portion having a second diameter, wherein the filter device is attached to tendons which extend through a cannula.FIG. 15 shows actuated or releasedtendons1450 and1460 attached or coupled todistal portion724 and cannula710 (e.g., such as described below inFIGS. 17 and 18) for transformingdistal portion724 from first diameter D11 to second diameter D21. Note that according to embodiments, diameter D11 may be a diameter similar to those described above with respect to first diameter D1 (seeFIG. 7 and accompanying text), and second diameter D21 may be a diameter similar to those described above with respect to second diameter D2.
• Actuated or releasedtendons1450 and1460 may be manipulated, such as by retracting or pullingtendons1450 and1460 indirection784 to movedistal portion724 indirections1186 and1188 to transform second diameter D21 into a third diameter, such as a diameter approximately equal to first diameter D11. For example,FIG. 16 is a side section view of a filter device with a distal portion having a third diameter and tendons attached to the distal portion and extending through a cannula. As shown inFIG. 16, reactuated or pulledtendons1470 and1480 are attached todistal portion724, pivot atpivot points1432 and1442, and extend throughcannula710, such thatdistal portion724 is transformed to third diameter D31. It is contemplated that third diameter D31 may be a diameter similar to those described above with respect to third diameter D30.
• Suitable actuation and/or manipulation tension fortendons1430 and1440 includes a range of tension between for example, zero pounds and five pounds such as a suitable tension for causing or countering an expansion pressure (e.g., such as caused bypressures730 and732) and or retraction pressure (e.g., such as described bypressures1140 and1141) as described above.
• According to embodiments,distal portion724 may also be retracted from the second diameter to approximately the first diameter by various other appropriate designs or systems including a self contracting filter device, such as using materials similar to the self expanding filter device described above, but having an opposite transformation principle. Likewise,distal portion724 may be retracted by a sheath such assheath790. Specifically, as shown inFIG. 9,sheath790 may be moved indirection985, to retract and cover overfilter device720 such as where the force of sheath moving in a distal direction causes retraction ofdistal portion724. Specifically,sheath790 may be moved indirection985 ofFIG. 9 until the configuration ofFIG. 7 is accomplished (e.g., withsheath790 overdistal portion724 of filter device720).
• Besides the above descriptions of retracting the second diameter ofdistal portion724, it is contemplated thatfilter device720 can be removed fromblood vessel990 without retraction of the second diameter. For example,distal portion724 may have a property such that it can be retracted indirection784 alongblood vessel990 without damaging or breachingblood vessel990. Specifically,distal portion724 may have atraumatic tips (e.g., such as by having properties at second diameter D2 as shown inFIG. 9, or atraumatic tips instead ofanchors1122 and1124 at positions shown inFIG. 12) such thatfilter device720 can be retracted indirection784 while having second diameter D2 or second diameter D20 under a second set of conditions. The tension ondistal portion724 is such that second diameter D20 may fluctuate (constrain or expand) asfilter device720 moves through one or more blood vessels.
• Note thatFIG. 14 also shows third angle A₃formed betweentendon1430 extending throughlumen710 and a point at whichtendon1430 is attached or coupled todistal portion724. For example, according to embodiments, third angle A₃shown inFIG. 14 may be an angle between 10° and 210°, such as an angle of 45°, 60°, 70°, 80°, 90°, 100°, 120°, and 125°.
• According to embodiments it is possible to mix technologies described above with respect to restrainingdistal portion724 by a retraction or contraction pressure, expandingdistal portion724 by an expansion pressure, and/or retractingdistal portion724 by a retraction or contraction pressure. For example, it is possible forfilter device720 andcannula710 to include a self expanding filter device, or balloon expanded filter device, restrained by tendons, wherein the distal portion offilter device720 may be expanded to a second diameter by self expansion or inflation of the balloons as described above, and then retracted to a third diameter by deflation of the balloons and/or manipulation of the tendons as described above. Likewise, it is possible forfilter device720 andcannula710 to include a self expanding filter device, or balloon expanded filter device, restrained by a sheath, wherein the distal portion offilter device720 may be expanded to a second diameter by self expansion or inflation of the balloons as described above, and then retracted to a third diameter by deflation of the balloons and/or manipulation of tendons attached to the distal portion, as described above.
• FIG. 17 is a front cross sectional view of the filter device ofFIG. 9 showing a proximal portion of the filter device axially attached to an exterior surface of a cannula andlumens extending through the cannula. As shown inFIG. 17,filter device720 hasdistal portion724 andproximal portion722 attached to an exterior surface ofcannula710. For example, in embodiments,FIG. 17 may be a front cross sectional view of a filter device and cannula from perspective “A” of FIGS.12 and/or15.FIG. 17 also showslumens1712,1714,1716, and1718 extending withincannula710, such as to extend fromproximal section712 ofcannula710 to a point distal toproximal portion722 of filter720 (SeeFIGS. 7, 9, and11-16, and accompanying text). In addition,lumen1740 is shown extending along inner surface of cannula1722 fromproximal section712 ofcannula710 to a point distal toproximal portion722 offilter720. It is to be appreciated thatlumens1712,1714,1716,1718, and/or1740 may exitcannula710 through exit holes or openings in the proximal end, distal end, and/or exterior ofcannula710, similar to howinflation lumen9540 extends fromproximal end9504 toballoon9510 and exits an inflation opening withinballoon9510, as described below with respect toballoon inflation lumen9540 of FIGS.69A-F. For example,lumens1712,1714,1716,1718, and/or1740 may be lumens sufficient for passing inflation gas and/or fluid through, such as for inflating and deflatingballoons1132,1134,1142, and/or1144 as described above (seeFIGS. 11-13 and accompanying text). Also,lumens1712,1714,1716,1718, and/or1740 may have a pivot point as any hole or opening where a lumen exitscannula710, such as by havingpivot point1432 or1442 at an opening where the lumen exits the exterior surface ofcannula710. Likewise,lumens1712,1714,1716,1718, and/or1740 may be lumens sufficient for extending, acuating, releasing, extending, maniuplating, and/or pullingtendons1430,1440,1450, and/or1460 therethrough (seeFIGS. 14-16 and accompanying text). Specifically,lumen1712 is shown inFIG. 17 withtendon1730 extended therethrough (e.g.,tendon1730 may be a tendon such astendon1430,1450, and/or1470).
• Furthermore, lumens described herein, such aslumen1712 andlumen1714 may provide for aspiration of particles, material, and matter as described above with respect to hole988 (e.g., seeFIG. 9 and accompanying text). Moreover,lumens1712,1714,1716,1718, and/or1740 may be include a surrounding material, sleeve, cannula or lumen, such as described below with respect toinfusion lumen9520 and/oraccessory lumen9530 of FIGS.69A-F
• In addition, according to embodiments, any or all oflumens1712,1714,1716,1718, and/or1740 may be used to inflate and/or deflate a balloon (e.g., such asballoons1132,1134,1142, and/or1144 as described above with resepect toFIGS. 11-13 and accompanying text) as well as have a tendon extending therethrough (e.g., such as for acuating, releasing, extending, manipulating, and/or pullingtendons1430,1440,1450, and/or1460 therethrough as described above with respect toFIGS. 14-16 and accompanying text). Specifically, for example,lumen1712 may be used for inflating and deflating balloons as described herein, as well as for having a tendon for actuation or manipulation as described herein, extending therethrough.
• Note that it is contemplated that balloons described herein will be inflated and deflated using fluids, including fluids described herein as a treatment agent. Likewise, it is also contemplated that lumens described herein, such aslumen1712 and1714, may provide the capability to inflate and/or deflate occlusion devices and balloons, to contain tendons, to contain guide wires, to provide for delivery of treatment agent, to provide for aspiration of treatment agent or particles, and/or to provide for pressure release, such as by providing those capabilities as described herein forfilter720, devices other thanfilter720, and/or at various regions of interest other than region ofinterest996. Thus, balloons1132,1134,1140,1141,1152, and1154 (SeeFIGS. 11-13, and accompanying text), as well aslumens1712,1714,1716,1718, and1740 may contain and provide sufficient pressure of a fluid, including a treatment agent, to inflate and deflate balloons as described herein.
• AlthoughFIG. 17 shows four lumens extending throughcannula710, according to embodiments, any number of lumens may be associated withcannula710,filter device720 other devices, and/or regions of interest as described herein. Constraints on the number of lumens that may be associated withcannula710, include the number lumen and/or cannula necessary for a particular purpose and the overall size (e.g, inner and/or outer diameter) of a system for delivery of a treatment agent to a region of interest. For example, in an embodiment wherefilter device720 has a helical spring shape, three lumen may be associated withcannula710 to restrain, actuate, manipulate, and/or extenddistal portion724 of the filter device. More particularly,FIG. 18 is a front cross sectional view of a filter device having a proximal portion axially attached to an exterior surface of a cannula, wherein the filter device has a helical spring shape.FIG. 18 shows filterdevice720 havingproximal portion722 axially attached to an exterior surface ofcannula710, whereinfilter device720 includeshelical spring shape1820.Helical spring shape1820 may providefilter device720 with a self-expanding frame, a self-contracting frame, and/or a frame portion (e.g., such as for having material stretched on the frame) as described herein.FIG. 18 also showslumens1812,1814, and1818 extending along the outer surface ofcannula710 fromproximal section712 ofcannula710 to a point distal toproximal portion722 offilter720.Lumens1812,1814, and/or1818 may be a lumen such as is described above with respect tolumen1712.
• The various configurations offilter device720 andlumen710 described herein can be used to restrain and aspirate particles, material, and matter as described above for a variety of catheters, including guide catheters, delivery catheters, guide wires, and other cannula. For example,FIG. 19 is a flow diagram of a process for using a filter device to restrain and aspirate particles. At block1910 a cannula, such ascannula710, is advanced percutaneously through a blood vessel, such asblood vessel990, wherein the cannula includes an exterior surface at or adjacent a distal end of the cannula axially coupled or connected to a proximal portion of a filter device, such asfilter device720. It is contemplated that the cannula may be advanced via a retrograde advancement, such as by being pushed up or down a blood vessel (e.g., such as a blood vein or artery) against or with a flow of blood. Specifically, the cannula may be advanced, such as from one blood vessel into a smaller blood vessel to provide retrograde infusion treatment, to a region of interest such as a region in a coronary sinus of a subject.
• Atblock1920, the distal diameter of a filter device, such as first diameter D1, is transformed or enlarged to a different second diameter, such as second diameter D2, that is approximately equivalent to an inner diameter of a blood vessel at a region of interest, such as diameter of vessel DV ofblood vessel990 at region ofinterest996. For example, first diameter D1 may be expanded indirections786 and788 to second diameter D2 until second diameter D2 approximates an inner diameter of a coronary sinus of a subject at a region of interest. Moreover, it is contemplated that second diameter D2 may be expanded sufficiently to make a pressure wave form in the blood vessel or coronary sinus become ventricularized.
• Atblock 1930 particles, material, and/or matter may be restrained from flowing through the filter device, such as by restraining a plurality of particles having a particle science greater than an average particle size of blood cells contained in blood flowing through the filter device. Thus, afterblock1920, it is contemplated that a liquid including a drug, treatment agent, infusion pellets, suspended cells, stem cells, microspheres, and/or other drugs or treatment agent mentioned herein may be delivered or infused through a lumen extending fromproximal section712 ofcannula710 to region of interest996 (e.g., to treatvessel990 at region of interest996). During or after delivery of the liquid, particles, material, and/or matter, such as described above, as well as stem cells, microspheres, metal, particles from devices, pieces of tissue, and/or other drugs or treatment agents mentioned herein may be restrained by the filter device, such as is described above with respect to filterdevice720.
• For instance, in one embodiment, at block1935 a treatment agent mentioned herein is infused to a region of interest of a blood vessel, such as described herein with respect toFIGS. 3, 63,69A-70, and82. Specifically, a treatment tagent may be infused to a region of interest via a delivery catheter disposed through a lumen extending fromproximal section712 todistal end714 ofcannula710, and extending to a region of a blood vessel, as described herein.
• Atblock1940 the restrained particles are aspirated. For example, a plurality of particles being restrained, such asparticles980, can be aspirated proximate to the exterior surface ofcannula710, such as is described above with respect tohole988 proximate todistal end714 and/or lumen1712 (e.g., seeFIG. 9 and accompanying text). It is contemplated that aspirating may occur during delivery of liquid and/or after delivery of liquid as described above atblock1930.
• Atblock1950 the distal diameter of the filter device is contracted. For example, second diameter D2 may be contracted or retracted to a diameter that is approximately that of first diameter D1 (e.g., such as third diameter D30, or D31 as described above) in response to a retraction pressure (e.g., such aspressure1140 and1141, or1451 and1461).
• Atblock1960 the cannula and attached filter device are retracted, such as by retracting or withdrawing the cannula back out ofvessel990 and out of the subject. For example, as noted above, it is contemplated thatcannula710 andfilter device720 may be retracted without modifyingdistal portion724 of filter device720 (e.g., to leavedistal portion724 at second diameter D2), or may be retracted or removed from the subject after transforming or contracting second diameter D2 to become approximately the first diameter (e.g., block1950).
• Note that according to embodiments, the process for usingfilter device720 to restrain and aspirate particles shown and described above forFIG. 19 may also apply for an apparatus similar toapparatus700 as shown inFIGS. 7-18, but having an occlusion device or balloon as described herein attached tocannula710 instead of and at the location offilter device720. Specificially, the process for usingfilter device720 ofFIG. 19 may have an occlusion device or balloon, instead offilter device720, enlarged atblock1920 and restraining particles and fluid atblock1930, by occluding the blood vessel, such as is shown and described with respect to balloon308 ofFIGS. 3A, 3B, and4. It can be appreciated that the other blocks ofFIG. 19 also apply to a process having an occlusion device or ballon in place offilter device720.
• Referring now toFIG. 20, there is illustrated a guide catheter.Guide catheter2000 hasdistal end2002 and proximal end (not shown). Adjacentdistal end2002 isocclusion device2006.Occlusion device2006 may be provided with self-expandingframe2010, andmaterial2012 stretched between frame structure or portions.Frame2010 may be made of an elastic material or a superelastic material, for example, nitinol or NiTi, wherein NiTi or a material described above with respect to forming the frame portion offilter device720. For example, guidecatheter2000 may be a guide catheter as described herein, such ascannula710 described forFIG. 7 above, andframe2010 may be a framed portion such as described above with respect to filter720 described forFIG. 7. Moreover, in one embodiment,material2012 may act as an occlusion device, such as by having no holes through it, and/or having a property such that fluid does not flow through it. For example,material2012 may include one or more of a synthetic or natural latex or rubber, such as a polymer material; a polyetheramide; a plasticiser free thermoplastic elastomer; a thermoplastic blend; a block copolymer of polyether and polyester (e.g., such as a polyester sold under the trademark Hytrel® of DUPONT COMPANY); a biocompatible polymer such as a polyether block amide resin (e.g., for instance, PEBAX® of ATOCHEM CORPORATION); a polycarbonate or acrylonitrile bubadiene styrene (ABS); a biocompatible polymer such as a polyether block amide resin; a styrene isoprene styrene (SIS), a styrene butadiene styrene (SBS), a styrene ethylene butylene styrene (SEBS), a polyetherurethane, an ethyl propylene, an ethylene vinyl acetate (EVA), an ethylene methacrylic acid, an ethylene methyl acrylate, an ethylene methyl acrylate acrylic acid, a material from a material family of one of styrenic block copolymers and polyurethanes, a melt processible polymer, a low durometer material, nylon, and other materials that can block fluid flow.
• Sheath2004, for example, a retractable or a tear-away sheath, such assheath790, is shown pulled away fromocclusion device2006 in direction ofarrow2014. Whenguide catheter2000 is deployed into a vessel (e.g., such as is described above with respect to deployment ofcannula710 forFIG. 7, and including a blood vessel of a subject orfluid flow2020 occurs in direction ofarrow2014.
• Distal end2005 of sheath may be coveringocclusion device2006. Afterdistal end2002 of catheter is located in a preferred location,sheath2004 may be moved in a proximal direction (e.g., a direction of arrow2014) to uncoverocclusion device2006. Thereafter, self-expandingframe2010 forcesopen device2006 in direction ofarrows2018 so thatocclusion device2006 occupies substantially the entire vessel. Any fluid flowing through vessel in direction ofarrows2020 must then pass throughmaterial2012, or be trapped bymaterial2012.
• In another embodiment, if guide catheter is placed in a vessel with fluid flow in the direction ofarrow2022, thenocclusion device2006 may be turned around so that opening2024 ofocclusion device2006 faces into the direction of fluid flow (e.g., see arrow2022). Therefore,frame2010 andfluid flow2020 or2022 serve to forceocclusion device2006 against the interior walls of a vessel (not shown). Aspiration side-hole2016 may be provided adjacentdistal end2002 inguide catheter2000 such as at a location and to function as is described above with respect tohole988 forFIG. 9 (e.g., distal to a proximal end of occlusion device2006). Thus, aspiration side-hole2016 may be used to aspirate fluid and/or particles from a vessel distal todevice2006.
• Referring now toFIG. 21, there is illustrated a telescoping guide catheter system. Telescoping guide catheter system includesouter guide catheter2100 having proximal end (not shown) anddistal end2101.Outer guide catheter2100 has an inner diameter adapted to containinner guide catheter2102, for example, the outside diameter ofinner guide catheter2102 is smaller than the inside diameter ofouter guide catheter2100, so thatouter guide catheter2100 andinner guide catheter2102 may be slidingly engaged.Inner guide catheter2102 has proximal end (not shown) anddistal end2103.Outer guide catheter2100 is provided withocclusion device2104 atdistal end2101, andinner guide catheter2102 is provided withocclusion device2112 atdistal end2103.
• As illustrated,occlusion device2104 includesframe2106, for example, an elastic frame, andmaterial2108 stretched between structure or portions offrame2106. For example,frame2106 may have a similar structure, functionality, and material as that described above forframe2010 ofFIG. 20. Likewise,material2108 may have a similar structure, functionality, and material as that described above formaterial2012 ofFIG. 20. There may also be provided a sheath (not shown) to coverocclusion device2104 until such time as it is to be deployed, and the same or a different sheath may be used for device recovery.Catheter2102 may also include aspiration side-hole2110 atdistal end2101, which may be used to aspirate fluid and/or particles distal toocclusion device2104, such as at a location and to function as is described above with respect tohole988 forFIG. 9. InFIG. 21,occlusion device2112 is shown asballoon2112, which may be any type of balloon or occlusion device as described herein such asocclusion device2006, or may be filter device such asfilter device720.
• Inner guide catheter2102 hasfirst curve2114, andouter guide catheter2100 hassecond curve2116. For example, according to embodiments,first curve2114 may be an angle between 10° and 125°, such as an angle of 10°, 20°, 30°, 45°, 60°, 80°, 90°, 100°, 120°, and 125°. Also, according to embodiments,second curve2116 may be an angle between 10° and 90°, such as an angle of 10°, 15°, 20°, 25°, 35°, 45°, 60°, 70°, 80°, and 90°. By slidinginner guide catheter2102 back and forth in direction of arrows2118 withinouter guide catheter2100, and rotatingouter guide catheter2100 and/orinner guide catheter2102,distal end2103 may be steered and tracked through a vessel network.
• Note that according to embodimentsproximate end712 ofFIG. 7, a proximate end ofguide catheter2000, and/or a proximate end ofguide catheter2100 may be attached to or extend to a guide catheter proximate portion, such as a proximate portion similar toproximate portion305 ofFIG. 3, and having the necessary holders, tracks, cannulas, lumens, and ports to provide for the functionality ofcannula710 ofFIG. 7, guidecatheter2000, and/or guidecatheter2100, or any other guide catheter as described herein.
• Referring now toFIGS. 22 and 23, there is illustrated the distal end and proximal end of a balloon catheter.Balloon catheter2200 may be a delivery or infusion catheter havingdistal end2202 andproximal end2203. Adjacentdistal end2202 of catheter isfirst balloon2204. Firstballoon inflation cannula2206 has a lumen there through and distal end includingfirst opening2208 withinfirst balloon2204 to inflate and/or deflatefirst balloon2204. There is also providedsecond balloon2250, withsecond balloon2250 distal tofirst balloon2204.First balloon2204 and/orsecond balloon2250 may be made of various appropriate natural rubber, polymer, lined ePTFE, thermoplastic blend, copolymer materials, having various appropriate dimensions, and being attached to balloon catheter220 by various procedures (e.g., such as laser bonding, adhesive bonding, and/or heat bonding) as described herein.
• First balloon2204 may be a distance fromsecond balloon2250 sufficient to block a proximal and a distal end of a region of interest, such as a region for delivering a treatment agent. For example, distance D defining a region for delivering a treatment agent betweenfirst balloon2204 andsecond balloon2250 may be a distance in the range between one centimeter and 20 centimeters, such as a distance of 10 centimeters.
• Moreover, according to embodiments,first balloon2204 and/orsecond balloon2250 may have a maximum inflated outer diameter of between two millimeters and 15 millimeters, such as by having an outer diameter during inflation of 10 millimeters. Furthermore, according to embodiments,first balloon2204 and/orsecond balloon2250 may employ a wedge or conical tapered shape, such as a shape having a tapered outer diameter towards distance D of four millimeters and an increasing diameter to a maximum diameter away from distance D of 10 millimeters. Thus it is possible to select balloons having a tapered profile to promote better sealing of a treatment region in a vessel as well as better centering of the balloons upon inflation. Likewise, the size and shape offirst balloon2204 andsecond balloon2250 may be selected to provide a treatment region that may be pressurized, such as by a pressurized infusion of treatment agent as described herein, while preventing the flow of infused treatment agents out of the treatment region. For example,second balloon2250 can be selected to prevent the flow of treatment agents out of a treatment region, such as defined within a blood vessel along distance D, whilefirst balloon2204 can be selected to prevent the backflow of infused treatment agents out of the treatment region and towardsproximal end2203. Next, the size, shape, and material offirst balloon2204 andsecond balloon2250 may be selected to establish a desired pressure gradient within a vessel at the location of proximate to or betweenfirst balloon2204 andsecond balloon2250. More particularly, size, shape, material, and inflation pressure offirst balloon2204 andsecond balloon2250 may be selected such that a treatment region as defined by distance D within a vessel may be pressurized, such as with a treatment agent, to a pressure between one and 30 atmospheres (e.g., such as to a pressure of between six and eight atmospheres).
• First balloon2204 andsecond balloon2250 may be the same shape, size, and/or material, orfirst balloon2204 may have a different shape, size, and/or material thansecond balloon2250. Secondballoon inflation cannula2256 has a lumen there through and includes distal end andsecond opening2258 withinsecond balloon2250 to inflate and/or deflatesecond balloon2250. In another embodiment, firstballoon inflation lumen2206 and secondballoon inflation cannula2256 are the same lumen, with twoopenings2208 and2258, while in another embodiment (as illustrated), firstballoon inflation lumen2206 is different than and not connected to secondballoon inflation cannula2256.
• Pressure-sensing cannula2210 has distal end andpressure sensing opening2212, which enables pressure-sensing, such as via a pressure sensing device as described herein with respect to fitting2548, or other measurements or parameters to be taken in a region of a vessel betweenfirst balloon2204 andsecond balloon2250, or where everdistal end2202 is placed.Delivery cannula2214 has distal end anddelivery opening2216 which enables a fluid or treatment agent path fromproximal end2203 ofballoon catheter2200 to opening2216 betweenfirst balloon2204 andsecond balloon2250.
• In one embodiment,balloon catheter2200 has a tapered tip. Tapered tip ofcatheter2200 may enable easier tracking ofdistal end2202 of catheter through a blood vessel. In one embodiment,distal end2202 may have tapered cut2222, which may be curved to have the profile shown inFIG. 22. Other configurations ofdistal ends2202 are envisioned which would ease tracking through a blood vessel. For example, taperedcut2222 may be at angle “A” with respect to the longitudinal axis ofcatheter2200, where angel “A” may be an angle between 10° and 90°, such as an angle of 10°, 15°, 20°, 25°, 35°, 45°, 60°, 70°, 80°, and 90°. Also, taperedcut2222 may have or form a tapered shape with respect to the longitudinal axis ofcatheter2200, where the tapered shaped may include one or more of a convex, a concave, and a three dimensionally shaped cut. Thus, taperedcut2222 can have angle “A” and a tapered shape sufficient to allowballoon catheter2200 to be fed through a vessel such as is described above with respect to feedingguide catheter302 through a vessel; and/or to be fed through another catheter such asguide catheter302 or502, such as is described above with respect todelivery catheter310 being fed throughguide catheter302.Balloon catheter2200 may have an outer diameter or outer dimension to fit within a guide catheter such asguide catheter302 or guidecatheter502. For example,balloon catheter2200 may have an outer diameter of between 5 French and 6 French and be capable of fitting within a guide catheter having an outer diameter of between 8 French and 9 French.
• Balloon catheter2200 may have one or more radio-opaque markers applied to its outer diameter, such as by adhesive, laser bonding, or heat bonding, and/or may include a filler such as barium sulfate added to the polymeric material used to formballoon catheter2200 neardistal end2202 to track the position ofdistal end2202. According to embodiments, such markers or filler may have various widths such as a width between one millimeter and two centimeters, and may extend around a portion of or completely around the circumference ofballoon catheter2200.
• For example,catheter2200 may also includemarker2230, for example, a radio-opaque marker, which may serve to ease visualization ofdistal end2202 ofcatheter2200 with a diagnostic visualization system. There may also be provided a second marker (not shown) adjacentsecond balloon2250, so thatfirst marker2230 and second marker (not shown) may be used to locatefirst balloon2204 andsecond balloon2250, respectively.
• Catheter2200 may also includeguidewire cannula2242 to extend fromproximal end2203 throughcatheter2200 toguidewire opening2243.Guidewire cannula2242 has distal end andguidewire opening2243, adjacentdistal end2202 ofcatheter2200.Guidewire cannula2242 has dimensions to receiveguidewire2244.Guidewire2244 is illustrated, whereguidewire2244 hasdistal end2246 andocclusion device2248 attached toguidewire2244 adjacent guidewiredistal end2246.Occlusion device2248 may be attached toguidewire2244 by various appropriate methods including laser bonding, adhesive bonding, thermal bonding and other bonding processes as described herein for attaching an occlusion device, such as a balloon, to a guidewire or catheter. In addition,balloon catheter2200 and guide catheter1002 may have a length such as is described above with respect to the length ofguide catheter302.
• FIG. 23 also shows firstballoon inflation cannula2206 attached to firstballoon inflation port2290, such as via adhesive bonding, heat bonding, threaded bonding or various other appropriate bonding processes for attaching firstballoon inflation port2290 sufficiently so that an appropriate volume and pressure of liquid may pass therethrough to inflatefirst balloon2204. Likewise, secondballoon inflation cannula2256 is attached to second balloon inflation port, such as is described above with respect to firstballoon inflation port2290.Pressure sensing cannula2210 is attached to pressuresensing port2294 similar to methods described above for attachingport2290 tocannula2206, and sufficiently to allow a volume in pressure of fluid to float throughpressure sensing port2294, such as to a pressure sensing device attached to pressuresensing port2294, such as is described herein with respect to a pressure sensing device as described herein with respect to fitting2548. Next,delivery cannula2214 is attached todelivery port2296, such as is described above with respect to attachment ofport2290 tocannula2206, and sufficiently for delivery of a volume and pressure of a liquid and/or treatment agent as described herein and to a region of interest, to provide a treatment or treatrnent region as described herein. Finally,guidewire cannula2242 is attached toguidewire port2298, similarly to the attachment described above for attachingport2290 tocannula2206, and sufficiently so that guidewire2244 can extend throughguidewire port2298 and can be manipulated, controlled, and used to place guidewiredistal end2246 and/orocclusion device2248 at a desired region within a vessel as described herein.
• FIG. 24 shows a section view ofFIG. 23 through line D-D′. As shown inFIG. 24, firstballoon inflation cannula2206, secondballoon inflation cannula2256,pressure sensing cannula2210,delivery cannula2214, andguidewire cannula2242 are shown disposed throughballoon catheter2200 such as fromproximal end2203 todistal end2202. Furthermore,guidewire2244 is shown fed through or disposed throughguidewire cannula2242, such as is described above. In another embodiment, guidewire and guidewire lumen (not shown) are in a monorail or OTW configuration. It is also contemplated that the guidewire and guidewire lumen (not shown) can te in a rapid-transfuser type configuration, such as illustrated inFIGS. 3 and 37, and described in accompanying text.
• FIG. 25 illustrates a catheter system.Catheter system2500 includesdelivery catheter2520 havingflexible shaft2522,distal end2524,proximal end2526, with a delivery lumen extending therebetween. For instance,delivery catheter2520 or any delivery catheter as described herein may have a distal end has an outer diameter less than about 10 mm, seven mm, five mm or three mm. In addition, according to embodiments,delivery catheter2520 or any delivery catheter as described herein may have a flexible shaft made of a bio-compatible polymer, a bio-compatible polymer having a durometer hardness of about 30 to about 100 shore D, a bio-compatible polymer having a durometer hardness of about 50 to about 70 shore D, a polyether block amide resin, and/or a flexible shaft that is radiopaque.Soft tip2530 is bonded todistal end2524 ofshaft2522. The delivery lumen extends from fitting2532 atproximal end2526 throughshaft2522 and throughsoft tip2530 tooutlet port2592 insoft tip2530. Note that a delivery lumen as described herein may have cross-sectional area suitable for advancing into a cardiovascular system of a patient and to deliver a treatment agent to a region of interest in a blood vessel of the patient. Suitable cross-sectional areas include at least about 0.95 mm², 2 mm², 3 mm², 5 mm², or 10 mm². One or more side holes in communication with the delivery lumen may also be provided neardistal end2524 ofshaft2522. Pressure increasingdevice2560 is shown attached to fitting2532.
• Catheter2520 is provided withballoon2547 ondistal end2524 ofcatheter2520, whichballoon2547 is adapted to occlude the coronary sinus or another vessel when inflated. An inflation lumen extends throughshaft2522 and is in communication with the interior ofballoon2547 throughopening2537. Specifically, the inflation lumen, or any other inflation lumen as described herein may be a balloon inflation lumen within a flexible tube or cannula shaft (e.g., such as a lumen having a surrounding material, sleeve, cannula or lumen, such as described below with respect toinfusion lumen9520 and/oraccessory lumen9530 of FIGS.69A-F). Nearproximal end2526, the inflation lumen is connected toinflation extension tube2538 attached toshaft2522 having fitting2540 at its proximal end shown attached toinflation device2564. Cptionally,pressure release valve2541 may be connected toinflation extension tube2538 to prevent over inflation ofballoon2547.Extension tube2538 may have a surrounding material, sleeve, cannula or lumen, such as described below with respect toinfusion lumen9520 and/oraccessory lumen9530 of FIGS.69A-F.
• A pressure lumen is also provided inshaft2522 which opens atpressure port2544 on side-wall ofshaft2522 neardistal end2524, or insoft tip2530 as illustrated. The pressure lumen is connected toextension tube2546 attached toshaft2522 nearproximal end2526.Extension tube2546 has fitting2548 at its proximal end shown connected to pressuremeasuring device2562.Extension tube2546 may have a surrounding material, sleeve, cannula or lumen, such as described below with respect toinfusion lumen9520 and/oraccessory lumen9530 of FIGS.69A-F.
• Pressure increasingdevice2560 is shown connected byconnection2572 tocontroller2570.Pressure measuring device2562 is shown connected tocontroller2570 byconnection2574.Inflation device2564 is shown connected tocontroller2570 byconnection2576.
• In one embodiment,distal end2524 ofcatheter2520 is inserted into a vessel, for example, the coronary sinus. Oncedistal end2524 ofcatheter2520 is in place,balloon2547 may be inflated byinflation device2564.Pressure measuring device2562 measures pressure distal toballoon2547 throughpressure port2544 on side-wall ofshaft2522. Once the pressure waveform in the vessel has become ventricularized, for example, blood beating againstballoon2547 in a similar rhythm to a heartbeat, inflation ofballoon2547 is stopped bycontroller2570. At this point,pressure increasing device2560 begins to force a liquid throughcatheter2520 tosoft tip2530 tooutlet port2592. Liquid is forced into the vessel distal toballoon2547.Pressure measuring device2562 measures pressure distal of balloon while liquid is being forced bypressure increasing device2560.Controller2570 controlspressure increasing device2560 to regulate fluid flow and pressure, by the information provided bypressure measuring device2562. After a sufficient period of time,controller2570 stops the delivery of liquid bypressure increasing device2560, then deflatesballoon2547 withinflation device2564, andcatheter2520 may then be removed from the vessel. It is worth explaining that although references are made herein to a pressure lumen and a pressure-sensing device (e.g., such as is describe above with respect toFIG. 25), it is considered that a pressure lumen, as described herein, can be used for measuring other parameters including flow, oxygen saturation, pH, and/or temperature. Similarly, a pressure-sensing device, as described herein, can be exchanged with another device to measure one of the parameters above. Moreover, althoughsystem2500 describes a catheter with three lumens, it is envisioned that a cannula or catheter as described herein (e.g., such as is describe above with respect toFIG. 25), may have four or more lumens. Specifically, a cannula or catheter as described herein, may include a balloon inflation lumen, a delivery lumen, and two parameter measurement lumens (e.g., such as one lumen to measure pressure and another lumen to measure temperature).
• Delivery catheter2620 is shown inFIGS. 26, 27,28 and29.Delivery catheter2620 includesflexible shaft2622 havingdistal end2624,proximal end2626 anddelivery lumen2628 extending therebetween. In one embodiment,shaft2622 is at least about 50 cm long, and in another embodiment, at least about 60 cm long, betweenproximal end2626 anddistal end2624, so thatdistal end2624 may be positioned in the coronary sinus or another vessel (as seen inFIGS. 33 and 34) withproximal end2626 extending out of the patient through a puncture in a peripheral vein, such as a femoral vein.Shaft2622 is made of a material such that it is sufficiently flexible to navigate this path without difficulty. In one embodiment,shaft2622 is made of a biocompatible polymer such as a polyether block amide resin, for example, PEBAX®, a registered trademark of Atochem, with a durometer in a range of about 50 to about 72 Shore D. In another embodiment, a portion, including the entire portion, ofshaft2622 is radiopaque to permit fluoroscopic observation thereof to facilitate positioning. Radiopaque markers may be applied to the shaft neardistal end2624, or a filler such as barium sulfate may be added to the polymeric material used to formshaft2622.
• To allow percutaneous introduction ofdelivery catheter2620 in a peripheral vein, in one embodiment,shaft2622 will have an outer diameter (“OD”) of no more than about 5.0 mm fromdistal end2624 to at least about 30 cm proximal thereto, and in another embodiment, to at least about 50 cm proximal thereto.
• In some embodiments, delivery cathters described herein (e.g., such asballoon catheter2200,delivery catheter2520, and/or delivery catheter2620) may be adapted for introduction through a commercially-available 9 French or 10 French introducer sheath or a suitably sized guide catheter, and/or by feeding over a guidewire, or for introduction by surgical cut-down into a comparably-sized blood vessel (e.g., such as an artery of vein, including a peripheral vein). Additionally, the delivery catheters described herein may be adapted to be introduced through guide catheters as described herein (e.g., such ascatheter302,502,2000, and/or2100) to be delivered to a location of a blood vessel from which the distal end of the delivery catheter (e.g., such asdistal end2524 or2624) may be advanced to a region of interest of a blood vessel to be treated by infusing a treatment agent (e.g., such as by infusion throughsystem2500, as described above).
• In one embodiment, a guide catheter (e.g., such as a guide catheter to be used with a delivery catheters described herein) is adapted to be fed into a femoral vein, then to an external iliac vein, then to a common iliac vein, to inferior vena cava116), then intoright atrium122, and into coronary sinus3286 (seeFIG. 32), and can then be fed further into venus system on exterior of heart (seeFIGS. 33 and 34). In another embodiment, guide catheter is adapted to be fed into an external jugular vein or an internal jugular vein, intosuperior vena cava126, and then intoright atrium122 and intocoronary sinus3286, where guide catheter may stay in coronary sinus3286 (seeFIG. 32), or be fed further into the venus system on exterior of the heart (seeFIGS. 33 and 34).
• In one embodiment, a suitable guide catheter is described in a co-pending patent application Ser. No. 10/293,535, filed on Nov. 12, 2002. Co-pending patent application Ser. No. 10/293,535, filed on Nov. 12, 2002 is herein incorporated by reference in its entirety. The guide catheter disclosed in the co-pending patent application may be inserted into a blood vessel, such as a femoral vein. Note that that guide catheter has a first convex curved portion, a concave curved portion distal to the first convex curved portion, and a second convex curved portion distal to the concave curve portion. Suitable guide catheters may also include an occlusion balloon at a distal end (e.g., such ascatheter302,502, and2100 havingballoons308,510, and2112, respectively). Other suitable guide catheters include the Viking Opima Line™ (a trademark of Guidant Corporation), the ACS Viking™ line of guide catheters (a trademark of Guidant Corporation), and the ACS RAD Curve™ line of guide catheters (a trademark of Guidant Corporation). Appropriate guide catheters also include EasyTrak® guiding catheters, Rapido™ guiding catheters, and telescoping guide catheters, for example, CS-MP REF7300 and CS-IC90 REF 666776-101.
• Referring again toFIGS. 26-29, soft tip2630 (of for example, PEBAX® with a durometer of 20 to 30 Shore D) is bonded todistal end2624 ofshaft2622 to reduce the risk of trauma to the coronary sinus or other vessels.Delivery lumen2628 extends from fitting2632 atproximal end2626 throughshaft2622 and throughsoft tip2630 tooutlet port2692 in the distal end ofsoft tip2630.Side holes2634 in communication withdelivery lumen2628 may also be provided neardistal end2624 ofshaft2622 as shown inFIG. 27. In one embodiment,delivery lumen2628 preferably has a cross-sectional area no less than about 4 mm²at any point betweenproximal end2626 andoutlet port2692 to facilitate delivery of treatment agent at sufficient flow rates while keeping the pressure at which the treatment agent is delivered low enough to avoid excessive hemolysis if there is a blood component of the treatment agent, as described more fully below. In one embodiment, the inner diameter (ID) ofdelivery lumen2628 is at least about 2.8 mm, and height H1 is at least about 1.8 mm.
• Catheter2620 is provided withballoon2647 ondistal end2624 ofcatheter2620 which is adapted to occlude the coronary sinus or another vessel (seeFIGS. 33 and 34) when inflated. In one embodiment,balloon2647 includes a biocompatible polymer such as a polyether block amide resin, for example, PEBAX® (a registered trademark of ATOCHEM CORPORATION, PUTEAUX, FRANCE). In another embodiment,balloon2647 is a biocompatible polymer blend of polyurethane and silicone, for example PurSil™ (a trademark of THE POLYMER TECHNOLOGY GROUP, BERKELEY, CALIFORNIA). In one embodiment,balloon2647 has an inflated diameter range of about four mm to about nine mm, an uninflated diameter of about three mm, and a working length of about six mm. For instance, a balloon as described above with respect toballoons308,510, and2112, may be inflated as described below with respect toballoons8810 and9510, and/or by an inflation device such asapparatus9700 or9800 ofFIG. 75A-81.
• In one embodiment,balloon2647 may be located at least about 15 mm fromdistal end2624 ofshaft2622 so that, during positioning, ifballoon2647 is pulled out of the coronary sinus, there is sufficient length ofshaft2622 distal to the balloon that will remain in the coronary sinus to eliminate the need to relocatedistal end2624 in the coronary sinus.
• In one embodiment,balloon2647 is formed by dipping a mandrel in liquefied polymer and curing as needed.Balloon2647 may be attached toshaft2622 by, for example, heat welding or an adhesive.
• Inflation lumen2636 extends throughshaft2622 and is in communication with the interior ofballoon2647 throughopening2637. Nearproximal end2626,inflation lumen2636 is connected toinflation extension tube2638 attached toshaft2622 having fitting2640 at its proximal end for attachment to an inflation fluid delivery device. In one embodiment,inflation lumen2636 is configured to allow delivery of inflation fluid or gas at a sufficient rate to fully inflateballoon2647 in about two seconds. In another embodiment,inflation lumen2636 has a height H2 of about 0.5-0.9 mm and a width W of about 0.9-1.3 mm.Inflation lumen2636 may alternatively be a coaxial lumen aroundshaft2622, enclosed by a separate tubular member (not shown).Extension tube2638 may have a surrounding material, sleeve, cannula or lumen, such as described below with respect toinfusion lumen9520 and/oraccessory lumen9530 of FIGS.69A-F.
• Optionally,pressure relief valve2641 may be connected toinflation extension tube2638 to prevent overinflation ofballoon2647, which might damage the tissue of the coronary sinus or another vessel.Pressure relief valve2641 is configured to open and relieve fluid pressure frominflation lumen2636 whenballoon2647 exceeds the maximum desired inflated pressure or diameter, e.g., about 9 mm. This may be accomplished bypre-inflating balloon2647 to the maximum inflated diameter withoutpressure relief valve2641 mounted to the delivery catheter, thereby plastically deformingballoon2647 to its fully inflated size.Balloon2647 is then collapsed onto the shaft by applying a vacuum toinflation lumen2636, andpressure relief valve2641 is mounted toinflation extension tube2638. In use, whendelivery catheter2620 is positioned in the coronary sinus, inflation ofballoon2647 to the desired inflated size will require relatively low pressure, e.g. less than about 0.5-2.0 psi. However, once the maximum inflated size is reached, the pressure will increase significantly, causingpressure relief valve2641 to open, thus preventing overinflation ofballoon2647. A suitablepressure relief valve2641 is available from, for example, Smart Products, Inc. of San Jose, Calif., under the name “Luer Check Valve.”
• In another embodiment,balloon2647 may be self-inflating, wherein the treatment agent itself acts as the inflation fluid forballoon2647, eliminating the need for aseparate inflation lumen2636 inshaft2622. In this embodiment,delivery lumen2628 communicates with the interior ofballoon2647 in such a way thatballoon2647 will inflate fully to occlude the coronary sinus only during delivery of treatment agent. For example, a fluid path betweendelivery lumen2628 andballoon2647 may be provided such that all or a major portion of the treatment agent delivered throughdelivery lumen2628 first enters the balloon to causeballoon2647 to inflate, before treatment agent flows into the coronary sinus through outlet holes inshaft2622 distal toballoon2647, or through outlet holes in the balloon itself. One way to accomplish this is by a reduction in the diameter of the lumen distal to balloon2647 such that a sufficient head pressure is established to inflateballoon2647 and administer a treatment agent fromshaft2622.
• Pressure lumen2642 may also be provided inshaft2622 which opens atpressure port2644 on side-wall ofshaft2622 neardistal end2624, or insoft tip2630 as illustrated.Pressure lumen2642 is connected toextension tube2646 attached (e.g., via adhesive) toshaft2622 nearproximal end2626 and includes fitting2648 at its proximal end suitable for connection to pressure monitoring equipment. In this way, pressure in the coronary sinus distal toballoon2647 may be monitored during treatment agent delivery to ensure that pressure within the coronary sinus is maintained at a safe level.Extension tube2646 may have a surrounding material, sleeve, cannula or lumen, such as described below with respect toinfusion lumen9520 and/oraccessory lumen9530 of FIGS.69A-F.
• Pressure relief valve (e.g., not shown, but such as relief valve2641) connected toinflation extension tube2638, may also be connected todelivery lumen2628 to ensure that treatment agent pressure does not exceed a predetermined level, avoiding hemolysis in the blood component of the fluid and/or protecting the coronary sinus from excessive infusion pressure. In one embodiment, pressure in the range of aboutzero to about five mmHg could be measure atport2644.
• As shown inFIG. 29, distal portion ofshaft2622 may includedelivery lumen2628,inflation lumen2636,pressure lumen2642, andguidewire lumen2691.Guidewire lumen2691 is adapted to receive a guidewire, where the guidewire may be used for navigating through the vasculature and/or the guidewire may be provided with a balloon on a distal end of the guidewire.
• As shown inFIG. 27, distal portion ofshaft2622 may includefirst bend2650 andsecond bend2652, which facilitate the placement ofdistal end2624 in the coronary sinus. In one embodiment,second bend2652 may be distance L2 of between about three mm and 10 mm in distance from distal end ofsoft tip2630, andfirst bend2650 may be a distance L₁of between 20 mm and 40 mm in distance proximal tosecond bend2652. First andsecond bends2650,2652 may subtend various angles depending upon patient anatomy and surgeon preference. In one embodiment configuration,first bend2650 subtends an angle A of between about 200 and about 70° relative to the longitudinal axis ofproximal portion2654 ofshaft2622. In another embodiment,second bend2652 may subtend an angle B of about 30° to about 40° relative to mid-portion2656 ofshaft2622.
• A liquid containing a treatment agent or drug, e.g., a caroporide solution, may be introduced intoproximal end2626 ofcatheter2620, which extends outside of the patient, under sufficient pressure so that the fluid containing the treatment agent can be forced to pass through the coronary sinus, through the capillary beds (not shown) in the patient's myocardium, and optionally through coronary arteries (not shown) and ostia associated with the respective coronary arteries (not shown) into the ascending aorta (not shown).
• In one embodiment,balloon2647 on the distal extremity ofcatheter2620 is inflated to occlude the coronary sinus or another vessel to prevent fluid loss into the right atrium. A liquid containing a treatment agent such as adenosine is directed throughcatheter2620 into the coronary sinus or another vessel and the pressure and volumetric flow rate of the treatment agent within the coronary sinus or another vessel are maintained sufficiently high (e.g. at least 100 ml/min at about 40 mm Hg) so that the treatment agent will pass through the coronary veins, and reaching the capillary beds, and optionally on to the coronary arteries (not shown) and out the ostia (not shown).
• Treatment agent is delivered throughdelivery catheter2620 at a flow rate sufficient to maintain desired treatment by periodic or continual infusions. However, treatment solution pressure within the coronary sinus or another vessel should be less than about 50 mm Hg to avoid tissue damage. In one embodiment, the treatment agent is a mixture of blood and a treatment agent such as an antioxidant, in one embodiment at a ratio or four parts blood to one part antioxidant solution (by volume). This antioxidant solution may be mixed into oxygenated blood.
• The treatment agent may be directed to fitting2632 on proximal end ofdelivery catheter2620, and delivered to the coronary sinus, or another vessel, in one embodiment at a flow rate of at least about 100 ml/min. and in another embodiment, at about 200 ml/min. If treatment agent includes a blood component, the pressure required to pump the treatment agent through the lumen of the delivery catheter (“pump pressure”) should not exceed 300 mmHg to avoid excessive hemolysis of the blood component. Treatment agent flow throughdelivery catheter2620 is maintained on a periodic basis, e.g., about every 15-30 seconds for 2-4 minutes, so long as the heart is to remain under treatment.
• Referring now toFIG. 30, another embodiment of a catheter system is illustrated.Catheter system3000 includes delivery catheter3020 (for example,delivery catheter2620,3122,3201,3510,3920, or any other catheter or cannula, as described herein).Delivery catheter3020 includes proximal ends3026 (for example,2626) and distal end3024 (for example,2624,3112,3260).Delivery catheter3020 includes a delivery lumen (not shown) (for example,2628, or any other delivery lumen, tube or cannula as described herein). Delivery lumen connects outlet port3092 (for example,2692,3162,3154,2628,3228,3992, or any other treatment agent delivery or infusion opening, exit, or port, as described herein) ondistal end3024 of catheter and has fitting3032 (for example,2632) onproximal end3026 of catheter. Fitting3032 may be connected to a pressure increasing device3050 (for example,5600,5700, or5800) by device outlet3004 (for example,5604,5718, or5818). Intermediate todevice outlet3004 and fitting3032 there may be located one or more (in series) of pressure-transferring device, pressure-maintaining, and/or pressure-dampening device3052 (for example,5900,6000,6100).
• Ondistal end3024 of catheter is located balloon3047 (forexample balloon8810,9510,filter device710, or any other balloon, occlusion device, or filter device as described herein) with inflation lumen (not shown) (for example,2636,3936, or any other inflation lumen, tube or cannula, as described herein), where inflation lumen has opening3037 (for example,2637,3172), which serves to inflate and/or deflateballoon3047. Inflation lumen is throughcatheter3020 from opening3037 (for example,2637,3172) to inflation extension tube3038 (for example,2638), which has fitting3040 (for example,2640) at the proximal end ofinflation extension tube3038. There is also optionally provided pressure relief valve3041 (for example,2641) adjacent to fitting3040. Inflation device3070 (for example,apparatus9700,9800 ofFIGS. 75A-81 or any other balloon or occlusion device inflation device, as described herein) may be connected to fitting3040.Extension tube3038 may have a surrounding material, sleeve, cannula or lumen, such as described below with respect toinfusion lumen9520 and/oraccessory lumen9530 of FIGS.69A-F.
• Delivery catheter3020 may also have a pressure lumen (not shown) (for example,2642,3142,3220;accessory lumen9530, or any other lumen, tube, or cannula capable of measuring pressure or inserting a pressure sensing device through, as described herein), where pressure lumen has pressure port3044 (for example,2644,3136,3228,3944) at distal end of pressure lumen. Pressure lumen extends frompressure port3044 to extension tube3046 (for example,2646).Extension tube3046 has fitting3048 (for example,2648) at proximal end ofextension tube3046. Pressure-sensing device3060 may be connected to fitting3048.Extension tube3046 may have a surrounding material, sleeve, cannula or lumen, such as described below with respect toinfusion lumen9520 and/oraccessory lumen9530 of FIGS.69A-F.
• In one embodiment,system3000 hascontroller3080, such as a controller (e.g., including an automatic, computer, or machine controller) adapted to control a pressure increasing device, a pressure-sensing device, and/or an inflation device as described herein. More particularly, pressure-sensing device3060 may be connected to pressure measurement connection3008 (for example,5708 or5808 ofFIGS. 57 and 58) ofpressure increasing device3050 bypressure measurement connection3062. Optionally, there may be providedsystem controller3080, for example, a computer or mini-computer, which is connected to pressure increasingdevice3050, pressure-sensing device3060, and/orinflation device3070. For example,system controller3080 may access a memory including instructions (e.g., such as machine readable instructions) to control a pressure increasing device, a pressure-sensing device, an inflation device, in infusion device, and/or any device or apparatus, as described herein. Specifically,controller3080 may be used to control inflation and/or deflation of a balloon to various outer diameters (e.g., seeFIGS. 55 and 68 herein, which illustrates a balloon outside diameter growth rate) by inflating a balloon as described herein with a selected inflation pressure or volume.
• Moreover,system controller3080 may be used to control an amount of treatment agent infused, a period of time during which treatment agent is infused, a period of time during which an occlusion device occludes a blood vessel (e.g., such as first period oftime9670, or a period of time that filter device720 (e.g., seeFIGS. 7-19 and accompanying text) is expanded within the blood vessel), and/or a period of time during which blood and/or treatment agent is allowed to perfuse or flow through a region of interest in a blood vessel (e.g., such as second period of time9680). Similarly,system controller3080 may be used to control a treatment process for infusion of a treatment agent into an artery or vein of a patient using devices, apparatus, methods, and/or processes described herein (e.g., such as according to the process described with respect toFIGS. 3, 19,54,55,63, and/or82).
• A suitable self-inflating balloon configuration is illustrated inFIG. 31.FIG. 31 illustrates the structure and operation ofself inflating balloon3147 andflow tip3148 ofcatheter3120. Pear shapedballoon3147 tapers gradually from its widest diameter to form distalcircular cuff3168, and tapers more quickly from its widest diameter to form proximalcircular cuff3170.Proximal cuff3170 coaxially receivescatheter body3122 and is attached thereto to form a fluid tight seal betweencuff3170 andcatheter body3122.Distal cuff3168 coaxially receives and attaches to flowtip3148.
• Plurality ofradial holes3172 extend through body ofcatheter3122 from withininfusion lumen3128, proximal of flowtip base plug3152, intointerior space3174 enclosed byballoon3147. Thus the flow of treatment agent throughcatheter3120 shown byarrows3190 exitsinfusion lumen3128 throughholes3172, entersballoon interior3174, flows intoflow channels3158 and exits eachflow channel3158 through its side exits3162, ordistal exits3154. The aggregate cross sectional area ofholes3172 fillingballoon interior3174 exceeds the aggregate cross sectional area offlow channels3158draining balloon interior3174, providing a positive pressure withinballoon interior3174 to keepballoon3147 inflated while the treatment agent flows throughcatheter3120.
• Pressure monitoring lumen3142 extends through one ofopen channels3158 viaextension tube3175.Extension tube3175 may have a surrounding material, sleeve, cannula or lumen, such as described below with respect toinfusion lumen9520 and/oraccessory lumen9530 of FIGS.69A-F. Extension tube3175 extends fromflow tip body3150, wherepressure monitoring lumen3142 exits flowtip body3150, through one offlow channels3158, and terminates proximally adjacent flow channel distal exit (not shown), to form pressure lumendistal opening3136. The pressure monitoring equipment (not shown) is thus in pressure communication with the inside of the coronary sinus or another vessel in which pressure lumendistal opening3136 is located. Because the pressure lumendistal opening3136 is recessed into theflow channel3158, there is less chance of it becoming occluded by the wall of the coronary sinus, or another vessel.
• Also note that stylet well3176 can coaxially sink intobase plug3152 offlow tip3148 for receiving a stylet (not shown), and providing additional reinforcement atdistal end3156 ofcatheter body3122 where the stylet (not shown) impactsbase plug3152 offlow tip3148.
• FIG. 32 depictscatheter3201 positioned withinheart100.Catheter3201 may be inserted percutaneously through a blood vessel, such as an artery or vein. Specifically,catheter3201 can be advanced through a percutaneous venus entry, such as through a femoral vein, andtip3212 is guided throughright atrium122 intocoronary sinus3286. Blood drains intoright atrium122 viasuperior vena cava126 andinterior vena cava116, and fromcoronary sinus3286 viacoronary sinus ostium3288. Moreover, blood drains from the myocardium tocoronary sinus3286 via greatcardiac vein3290 and smallcardiac vein3292.
• Tip3212 havingport3214 is inserted intocoronary sinus3286 to a depth from about zero to about four inches (zero to about 10.2 cm) fromcoronary sinus ostium3288. Optionally,markers3218 may be provided oncatheter3201 and optionally spaced about two inches apart alongcatheter3201; in one embodiment,markers3218 are radiopaque.
• Referring now toFIG. 33, which illustrates diaphragmatic surface of heart3300.Coronary sinus3286 is shown feeding into right atrium. Great cardiac (anterior interventricular)vein3290, oblique vein ofleft atrium3310, and posterior vein ofleft ventricle3304 feed intocoronary sinus3286. Also, middle cardiac (posterior interventricular)vein3306, and smallcardiac vein3308 feed intocoronary sinus3286. All the veins are provided with arrows to show direction of ordinary blood flow intocoronary sinus3286 and into right atrium.
• Referring now toFIG. 34, sternocostal surface ofheart3301 is shown. Great cardiac (anterior interventricular)vein3290 is shown, as are anterior cardiac veins ofright ventricle3314, and smallcardiac vein3308.
• Leftcoronary artery3320 and rightcoronary artery3322 feed out ofaorta3350. Branching off of leftcoronary artery3320 are circumflex branch of leftcoronary artery3324, and anterior interventricular branch (left anterior descending) of leftcoronary artery3344, and interventricularseptal branches3326. Feeding off of rightcoronary artery3322 are atrial branch of rightcoronary artery3330, and right marginal branch of rightcoronary artery3328.
• Referring again toFIG. 33, rightcoronary artery3322 is shown. Feeding off of rightcoronary artery3322 are rightmarginal branch3338, and interventricularseptal branches3342. Other branches from left coronary artery (3320 inFIG. 34) are circumflex branch of leftcoronary artery3324, and posteriorleft ventricular branch3340. Also shown inFIG. 33 are sinuatrialnodal branch3332, andsinuatrial node3334.
• FIG. 35 illustratesdistal end3560 ofcatheter3510 withincoronary sinus3286.Catheter3510 hastip3514 atdistal end3560, and plurality oflumen outlets3528 proximal to tip3514.Balloon3522 is shown occludingcoronary sinus3286 andcoronary sinus ostium3288 adjacent toright atrium wall3556.Balloon3522 oncatheter3510 may also be used to occlude other veins distal tocoronary sinus3286, for example, greatcardiac vein3290, anterior cardiac vein ofright ventricle3314, and small cardiac vein3308 (shown inFIGS. 33 and 34). In this embodiment, a self-inflating balloon is shown withinfusion lumen3518 through which a treatment agent flows and inflatesballoon3522 then flows out oflumen outlets3528. Pressure-sensing lumen3520 is also provided. In another embodiment, a third lumen was provided (not shown) to inflateballoon3522 whenballoon3522 is not self-inflating. There is also providedguidewire3570, havingdistal end3576.Guidewire3570 is fed throughguidewire lumen3572, whichguidewire lumen3572 hasdistal opening3574 attip3514.
• Referring now toFIG. 36 is a staggered tip of a balloon catheter.Balloon catheter3600 hasdistal end3602 and proximal end (not shown). Adjacentdistal end3602 of catheter isballoon3604.Balloon inflation lumen3606 has distal end andopening3608 withinballoon3604 to inflate and/or deflateballoon3604. Pressure-sensing lumen3610 has distal end andopening3612 which enables pressure-sensing lumen3610 to sense pressure or other measurements or parameters whereverdistal end3602 of catheter is placed.Delivery lumen3614 has distal end andopening3616 which enables a fluid path from proximal end (not shown) of catheter todistal end3602 of catheter.
• Staggered tip ofcatheter3600 may enable easier tracking ofdistal end3602 of catheter through a blood vessel. In one embodiment, pressure-sensing lumen3610 and/orcatheter body3620 adjacent pressure-sensing lumen3610 have tapered cut3622 which may be curved. According to embodiments, taperedcut3622, may have an angle and a tapered shape, such as is described above with respect totapered cut2222 ofFIG. 22. In one embodiment, distance L, marked withreference numeral3624 is the distance betweendistal end3612 of pressure-sensing lumen3610 anddistal end3616 ofdelivery lumen3614. In one embodiment, L,3624 may be between about 0.5 millimeters and five millimeters.
• In another embodiment,catheter3600 is illustrated. Catheter hasballoon inflation lumen3606,balloon3604,delivery lumen3610 havingopening3612, and pressure-sensing lumen3614 havingopening3616.Catheter3600 has a staggered tip whereopening3612 ofdelivery lumen3610 isdistance L₁3624 from opening3616 of pressure-sensing lumen3614. In addition,catheter body3620adjacent opening3612 ofdelivery lumen3610 may have a tapered and/orcurved shape3622.
• In another embodiment,catheter3600 may includemarker3630, for example a radio-opaque marker, which may serve to ease visualization ofdistal end3602 ofcatheter3600 with a diagnostic or visualization system.
• Referring now toFIG. 37, is a staggered tip of a balloon catheter.Balloon catheter3700 hasdistal end3702 and proximal end (not shown). Adjacentdistal end3702 of catheter isballoon3704.Balloon inflation lumen3706 has distal end andopening3708 withinballoon3704 to inflate and/or deflateballoon3704. Pressure-sensing lumen3710 has distal end andopening3712 which enables pressure-sensing lumen3710 to sense pressure or other measurements or parameters whereverdistal end3702 of catheter is placed.Delivery lumen3714 has distal end andopening3716 which enables a fluid path from proximal end (not shown) of catheter todistal end3702 of catheter. Staggered tip ofcatheter3700 may enable easier tracking ofdistal end3702 of catheter through a blood vessel. In one embodiment, pressure-sensing lumen3710 and/orcatheter body3720 adjacent pressure-sensing lumen3710 have tapered cut3722 which may be curved. According to embodiments, taperedcut3722, may have an angle and a tapered shape, such as is described above with respect totapered cut2222 ofFIG. 22. There is also provided anindentation3740 proximal todistal end3702, withguidewire lumen3742 distal toindentation3740.Indentation3740 andguidewire lumen3742 are adapted to receiveguidewire3744.Guidewire3744 has proximal end (not shown) anddistal end3746.Guidewire3744 may be provided withballoon3748 adjacentdistal end3746. In use,catheter3700 may be tracked over the guidewire through by feedingdistal end3702 of catheter overguidewire3744 by way oflumen3742. This “over the wire” (OTW) is also known as monorail.
• Referring now toFIG. 38, the staggered tip of a balloon catheter.Balloon catheter3800 hasdistal end3802 and proximal end (not shown). Adjacentdistal end3802 of catheter isballoon3804.Balloon inflation lumen3806 has distal end andopening3808 withinballoon3804 to inflate and/or deflateballoon3804. Pressure-sensing lumen3810 has distal end andopening3812 which enables pressure-sensing lumen3810 to sense pressure or other measurements or parameters whereverdistal end3802 of catheter is placed.Delivery lumen3814 has distal end andopening3816 which enables a fluid path from proximal end (not shown) of catheter todistal end3802 of catheter.
• Staggered tip ofcatheter3800 may enable easier tracking ofdistal end3802 of catheter through a blood vessel. In one embodiment, pressure-sensing lumen3810 and/orcatheter body3820 adjacent pressure-sensing lumen have tapered cut3822 which may be curved. According to embodiments, taperedcut3822, may have an angle and a tapered shape, such as is described above with respect totapered cut2222 ofFIG. 22. In one embodiment, distance L₁marked withreference numeral3824 is the distance betweendistal end3812 of pressure-sensing lumen3810 anddistal end3816 ofdelivery lumen3814. In one embodiment,L₁3824 may be between about 0.5 mm and about five mm.
• Catheter3800 may also includemarker3830, for example, a radio-opaque marker, which may serve to ease visualization ofdistal end3802 ofcatheter3800 with a diagnostic visualization system.
• Catheter3800 may also includeguidewire lumen3842 throughcatheter3800.Guidewire lumen3842 has distal end andopening3843 adjacentdistal end3802 of catheter.Guidewire lumen3842 is adapted to receive a guidewire.Guidewire3844 is illustrated, whereguidewire3844 hasdistal end3846 andballoon3848 adjacentdistal end3846.
• Referring now toFIG. 39, which showscatheter3920 within blood vessel3910 (e.g., such as a vein or artery).Catheter3920 includesballoon3947 ondistal end3924 ofcatheter3920. Also, ondistal end3924 isoutlet port3992 to deliver a treatment agent intoblood vessel3910.Pressure port3944 is ondistal end3924 to measure a pressure inblood vessel3910.Balloon3947 is inflated by outlet ports ofinflation lumen3936.Blood vessel3910 is divided into two portions,first portion3914 is distal toballoon3947, andsecond portion3912 is proximal toballoon3947.Balloon3947 serves to seal against inner wall ofblood vessel3910, and provide a pressure separation betweenfirst portion3914 andsecond portion3912. In one embodiment, treatment agent flowing throughoutlet port3992 serves to increase the size offirst portion3914 due to the high pressure exerted by treatment agent on blood vessel walls infirst portion3914. This causesfirst portion3914 to have a larger diameter thansecond portion3912, and a frusto-conical shape taper is created betweenfirst portion3914 andsecond portion3912. In this embodiment,balloon3947 is tapered to accommodate the frusto-conical shape of the taper betweenfirst portion3914 andsecond portion3912.
• In one embodiment,balloon3947 may be tapered by havingdistal end3949 of balloon have a thinner wall thickness thanproximal end3951 ofballoon3947, so that fluid or gas inserted intoballoon3947 through outlet port ofinflation lumen3936 serves to make thedistal end3949 of balloon larger thanproximal end3951 ofballoon3947. In another embodiment,balloon3947 may have uniform wall thickness ofproximal end3951 anddistal end3949, but the balloon is molded and/or formed in a tapered shape, or otherwise formed so thatballoon3947 will assume a tapered shape when inflated.
• In one embodiment, a pressure-sensing device may be connected to pressureport3944 via an attachment to fitting3648 at proximal end ofextension tube2646 of catheter2620 (shown inFIGS. 26-29). In one embodiment, pressure-sensing device may be attached to proximal end of pressure lumen2642 (shown inFIG. 28-29). In another embodiment, a pressure-sensing device may be fed throughpressure lumen2642 adjacent to pressureport2644 on side-wall ofshaft2622 neardistal end2624 of catheter2620 (shown inFIGS. 26-29). In one embodiment, pressure-sensing device is disposable. In another embodiment, pressure-sensing device is a disposable piezo-electric pressure sensor, for example, a piezo-electric pressure sensor manufactured by Utah Medical Products, Inc., which is attached to fitting2648 (shown inFIG. 26).
• In one embodiment, an inflation device may be connected toinflation lumen3936 via attachment to fitting2640 at proximal end ofinflation extension tube2638 attached toshaft2622 andinflation lumen2636 extending throughcatheter2620. In one embodiment, the inflation device is a syringe. In another embodiment, the inflation device is a pump, for example, a centrifugal pump, a gear pump, or a reciprocating pump. In another embodiment,balloon2647 is inflated with carbon dioxide, saline, and/or contrast medium by the inflation device.
• Referring now toFIG. 40, is illustratedguidewire4000.Guidewire4000 hasdistal end4002. Atdistal end4002 isballoon4004.Balloon4004 may be inflated and/or deflated byballoon inflation lumen4006 thoughguidewire4000.Balloon inflation lumen4006 has distal end andopening4008 withinballoon4004. There may be provided one ormore markers4010 to aid visualization, for example under fluoroscopy, atdistal end4002 of guidewire.Spring4012 is provided about guidewire atdistal end4002 to improve tracking ofdistal end4002 through curves. In one embodiment,spring4012 imparts a natural curve todistal end4002.Tip4014 is provided to minimize damage to vessels astip4014 travels through vessels.Tip4014 hasdiameter L₁4016. In one embodiment, L, is between about 0.005 inches and 0.025 inches.
• Referring now toFIG. 41,guidewire4100 hasproximal end4101 anddistal end4102. For ease of illustration,break4103 is provided. Guidewire has sheath4106 (e.g., such assheath790 as shown and described with respect toFIGS. 7-9) about guidewire fromproximal end4101 todistal end4102.FIG. 41 showssheath4106enclosing occlusion device4108.Distal end4102 also includesfloppy tip4104.FIG. 42A illustrates the guidewire ofFIG. 41 with the occlusion device open. As shown inFIG. 42A,sheath4106 has been laterally moved in the direction ofarrows4110 to uncoverocclusion device4108.Distal end4102 of guidewire is withinvessel4112.Vessel4112 has fluid flow in the direction of arrow4113. Whensheath4106 is moved, to uncoverocclusion device4108, fluid flow withinvessel4112 forcesopen occlusion device4108 in the direction ofarrows4109.Occlusion device4108 then occludes vessel4112 (e.g., such as by since occlusion device being forced against vessel wall by fluid flow within vessel4112). Suitable materials forocclusion device4108 may include one or more of a synthetic or natural latex or rubber, such as a polymer material; a polyetheramide; a plasticiser free thermoplastic elastomer; a thermoplastic blend; a block copolymer of polyether and polyester (e.g., such as a polyester sold under the trademark Hytrel® of DUPONT COMPANY); a biocompatible polymer such as a polyether block amide resin (e.g., for instance, PEBAX® of ATOCHEM CORPORATION); a polycarbonate or acrylonitrile bubadiene styrene (ABS); a biocompatible polymer such as a polyether block amide resin; a styrene isoprene styrene (SIS), a styrene butadiene styrene (SBS), a styrene ethylene butylene styrene (SEBS), a polyetherurethane, an ethyl propylene, an ethylene vinyl acetate (EVA), an ethylene methacrylic acid, an ethylene methyl acrylate, an ethylene methyl acrylate acrylic acid, a material from a material family of one of styrenic block copolymers and polyurethanes, a melt processible polymer, urethane, polyurethane, polyethylene, polypropylene, polybutylene, copolymers of ethylene, propylene, butylene, a low durometer material, nylon, and other materials that can block fluid flow.
• FIG. 42B, is a front view ofFIG. 42A from perspective “A”.FIG. 42B shows an embodiment ofocclusion device4108 having overlapping leaflets.First leaflet4120 is shown overlappingsecond leaflet4122 from the front.FIG. 42C, is a side of the occlusion device ofFIG. 42A showing the occlusion device overlapping leaflets.FIG. 42C showsocclusion device4108 withsecond leaflet4120 overlappingfirst leaflet4122 from the back. In another embodiment, occlusion device4208 is a single member, without leaflets. For instance,occlusion device4108 may be a single member with fold lines to prevent crimping ofocclusion device4108 when retracted by sheath4106 (e.g., such as iffilter device720 were a solid member or material).
• In use,distal end4102 ofguidewire4100 is fed intovessel4112. Oncedistal end4102 of guidewire has been located in the correct position,sheath4106 may be pulled back in the direction ofarrows4110 to exposeocclusion device4108. Fluid flow in the direction of arrow4113, withinvessel4112, forcesopen occlusion device4108 in the direction ofarrows4109 to occludevessel4112. At the end of the procedure,sheath4106 may be advanced in the direction ofarrows4111 to recover or disengageocclusion device4108 and force it closed. At that point,distal end4102 may be removed fromvessel4112. In another embodiment, prior to removingdistal end4102,sheath4106 may be removed, and a second sheath (not shown) may be fed overproximal end4101 of guidewire to recoverocclusion device4108. Second sheath may have a larger diameter to trap fluid, particles, and/or foreign objects which were caught inocclusion device4108. In this embodiment, second sheath (not shown) is fed in direction ofarrows4111 untilocclusion device4108 has been closed and thendistal end4102 may be removed fromvessel4112.
• In one embodiment,occlusion device4108 may be provided with leaflets and/or fold lines to ease deployment and recapture of occlusion device. For instance, in one embodiment,occlusion device4108 may be opened (such as aftersheath4106 has been pulled back) by rotation ofguidewire4100 to causeocclusion device4108 to rotate indirection4182 to open occlude vessel4112 (seeFIGS. 42A-42C). Specifically, rotation ofocclusion device4108 indirection4182 causes leaflets of the device (e.g., including first andsecond leaflets4120 and4122) to open. Similarly,occlusion device4108 may be closed, such as for removal, by rotation ofguidewire4100 to causeocclusion device4108 to rotate indirection4184 to recover or disengageocclusion device4108 by forcing it closed (seeFIGS. 42B-42C). Thus, rotation ofocclusion device4108 indirection4184 causes leaflets of the device (e.g., including first andsecond leaflets4120 and4122) to close or form a smaller outer diameter than shown inFIG. 42A.
• Referring now toFIG. 43,guidewire4300 is illustrated having aproximal section4301 anddistal end4302.Occlusion device4304 is provided adjacentdistal end4302.Occlusion device4304 has aframe4306, andbasket4308 stretched between the structure offrame4306. For instance,frame4306 is shown havingdistal frame4362 andproximal frame4364 to supportbasket4308, such as wherebasket4308 forms a scoup, cone, “parachute”, or net shape betweendistal frame4362 andproximal frame4364 by being on, over, between, or attached todistal frame4362 andproximal frame4364. Suitable materials forbasket4308 include urethane, polyurethane, polyethylene, polypropylene, polybutylene, copolymers of ethylene, propylene, and/or butylene, latex, elastomers, PEBAX®, nylon and other materials that can block fluid flow. Also, suitable materials forframe4306 include an elastic material, nitinol (NiTi), and/or self-expanding materials (e.g., such as shape memory alloys, including for example, Nickel-Titanium) or other materials that have shape memory where the memorized shape is the expanded shape. To modify the shape (e.g., to restrict the shape) a sheath may be placed overocclusion device4304. Removing the restriction will allow the shape memory material to return to its memorized shape (e.g., an expanded shape) without being damaged. In the case shown byFIG. 43,sheath4310 is provided overguidewire4300 to be place over and/or restrain occlusion device4304 (e.g.,sheath4310 may be a material and/or function as described above forsheath790 or4106 as described above with respect toFIGS. 7-9, and41 respectively).
• According to embodiments,basket4308 may be connected or attached to aframe4306, such as by laser bonding, adhesive bonding, thermal bonding, mechanical restriction (e.g., such as ifmaterial basket4308 is woven or sewn through structure of the frame, such as structure including gaps between the structure or holes in the frame), and or various other appropriate attachment methods as described herein. Likewise, an inner diameter of theframe4306, such as in inner diameter ofproximal frame4364, may be attached to an outer surface ofguidewire4300, such as by laser bonding, adhesive bonding, thermal bonding, mechanical bonding.
• In use,distal end4302 is placed withinvessel4312, withsheath4310covering occlusion device4304. Whendistal end4302 is located in an appropriate location,sheath4310 is pulled back, andframe4306, which includes an elastic or expanding material to apply an expaning force toocclusion device4304, forcesopen occlusion device4304stretching basket4308 acrossvessel4312 to occlude fluid flow. In addition, fluid flow in the direction ofarrow4314 forcesopen occlusion device4304 and acts to pressbasket4308 against the walls ofvessel4312, by also applying a force on the inside surfaces ofbasket4308 which creates an expaning force toocclusion device4304.
• According to embodiments, occlusion devices may include various types of balloons made of various materials and according to various manufacturing techniques. For example, in one embodiment,devices720,2006,2104,4108,4304 as described herein;balloons308,314,510,2112,2204,2250,2547,2647,3047,3147,3522,3604,3704,3804,3947,4004,4420,4520,4820,8810,9510 as described herein; and/or any other catheter, cannula, tube, sheath, balloon or occlusion device, as described herein, may be made from or include a polymer material, such as a synthetic or natural latex or rubber. Moreover, the polymer material may be a polyether block amide resin, a polyetheramide, or a plasticiser free thermoplastic elastomer, for example, PEBAX®, a registered trademark of Atochem. Similarly, balloons or occlusion devices described herein may be made from or include a blend of different types of PEBAX®. In one embodiment, balloons or occlusion devices described herein may be made from or include a styrenic block copolymer (SBC), or a blend of SBC's. Suitable SBC's include SBC's sold under the tradename Kraton Polymers® a registered trademark of Shell Oil Company, SBC's sold under the tradename Vector® a registered trademark of Dexco Polymers, and SBC's sold under the tradename Europrene® a registered trademark of Polymeri Europa.
• In fact, in some embodiments, balloons mentioned above, or other balloons or occlusion device, as described herein, may include various types of a high-compliance and/or low-tension balloons, such as a composite or multi-layer expanded PolyTetraFlouroEthylene (ePTFE) balloon having an inner liner. For example,FIG. 44 is a cross-sectional view of a cannula and a balloon. As shown inFIG. 44, cannula4410 (e.g., such as a cannula having a dimension suitable for percutaneous advancement through a blood vessel, such as advancement in direction4586 through blood vessel4490) includesproximal end4412,distal end4414, andexterior surface4416.FIG. 44 also shows balloon4420 (e.g., such as balloon mentioned above, or another balloon or occlusion device, as described herein) axially connected toexterior surface4416 ofcannula4410, at or adjacentdistal end4414. Also shown are diameter of cannula DC, pre-inflation diameter of balloon DM, inflated diameter of balloon D2, post-inflation deflated diameter of balloon DP, and diameter of vessel DV.
• According to embodiments,balloon4420 may have a property such that when inflatedballoon4420 will expand in size to an outer diameter sufficient for occlusion of a blood vessel at an inflation pressure (and/or at an inflation volume as described herein with respect toballoon8810 and/orapparatus9700 or9800 ofFIGS. 75A-81) and less than sufficient to cause an axial force on an inner diameter of the blood vessel. For instance,FIG. 44 showsballoon4420 inflated to outer diameter D2 sufficient for occlusion ofblood vessel4490 at inflation pressure PR, which is a pressure less than sufficient to cause an axial force, such as a force indirections4487, oninner diameter4492 ofblood vessel4490.
• More particularly,balloon4420 may include a property such that when inflated to volume V1,balloon4420 will expand in size to outer diameter D2 that is approximately inner diameter DV ofblood vessel4490 at inflation pressure PR, which is a pressure less than sufficient to exert an axial strain onblood vessel4490 indirections4487. Thus,balloon4420 may be a high-compliance balloon that expands radially and longitudinally upon inflation and forms a plurality of radial outer diameters during inflation to an outer diameter sufficient to occlude the blood vessel at an inflation pressure that does not appreciably expand the blood vessel radially (e.g., such as by occluding the blood vessel at a location while the inner diameter of the blood vessel at the location stays within five percent its pre-occlusion inner diameter). Furthermore,balloon4420 may be a low-tension balloon, such as a balloon that expands radially and longitudinally upon inflation and forms a plurality of radial outer diameters during inflation and deflation, but does not form wings. For example,balloon4420 may have a balloon pre-inflated outer diameter DM between three mm and five mm at an inflation pressure of between zero atmospheres and one atmosphere in pressure, and a balloon inflated outer diameter D2 between five mm and nine mm at an inflation pressure between six atmospheres and eight atmospheres in pressure. In addition, according to embodiments, pressure PR may be a pressure sufficient to causeballoon4520 to occlude the blood vessel without radially expanding the blood vessel.
• In addition, balloon may have a property to cause post-inflation deflated outer diameter DP ofballoon4420 to retract to within 20% of pre-inflated outer diameter DM ofballoon4420. It is also contemplated thatballoon4420 may include one or more of the following characteristics: effective modulus of less than 1.5 MPa (e.g., such as during insertion into a blood vessel, use as an occlusion device, and removal from the blood vessel), and elongation of less than 500% at breaking, a tension set of less than 30%, a tension strength of at least 200 MPa, and an inflation range of pressure between zero and six atmospheres in pressure. In one embodiment,balloon4420 may have a tension set of less than 30% in residual strength after elongation to 300%, such as by having a tension set of 20%, 15%, 10%, or 5%. Specifically, according to one embodiment,balloon4420 may have a property to withstand an inflation pressure of between six and eight atmospheres of pressure and retract to within 20% ofballoon4420's initial pre-inflation dimension, upon removal of inflation pressure.
• It is also contemplated thatballoon4420 may have a wall thickness that varies with respect to the axis ofcannula4410, so that whenballoon4420 is inflated, it has a tapered profile. For instance, according to one embodiment,balloon4420 has a first wall thickness at firstaxial distance4432 fromdistal end4414 of the cannula and a different second wall thickness at different secondaxial distance4434 fromdistal end4414 ofcannula4410. Thus, whenballoon4420 is inflated, it will expand to a first outer diameter atdistance4432 and a different second outer diameter atdistance4434.
• Similarly, it is contemplated thatballoon4420 may have a pre-inflated outer diameter that varies along the axis ofcannula4410 so that whenballoon4420 is inflated, it has a tapered profile. In one embodiment, when deflated,balloon4420 has a first pre-inflated outer diameter atdistance4432 and a second pre-inflated outer diameter atdistance4434. Thus, when inflated,balloon4420 will expand in size to a first outer diameter atdistance4432 and a different second outer diameter atdistance4434. An illustration of a balloon having a tapered profile is shown inFIG. 39.
• In accordance with embodiments,balloon4420 may be formed by various appropriate processes. For example,balloon4420 may be formed by injection molding a material, extruding a material, solvent casting a material, and/or dip coating a material to form a balloon. Moreover, it is contemplating that extruding may include extruding a material such thatballoon4420 has a deflated outer diameter in a range of between 0.5 mm and five mm in diameter. For instance, material may be extruded such thatballoon4420 has a deflated outer diameter of 1.5 mm, and a thickness sufficient to reach an inflated outer diameter of nine mm at less than six atmospheres of inflation pressure.
• Furthermore, in embodiments,balloon4420 may include one or more of a silicone rubber; a polyurethane such as Pursil™, or another biocompatible silicone polyether urethane; Pebax™ such as polyether-block co-polyamide polymer, polyether-block anide; diene polymers and their copolymers; isoprenes; neoprenes; diene; styrene; butadienes; styrene-isoprene-styrene block co-polymers; styrene-butadiene-styrene co-polymers; partially or fully crosslinked versions of these same polymers, such as a Kraton™ (e.g., such as Kraton™1161K, which is a styrene-isoprene-styrene tri-block co-polymer with 85% isoprene and 15% styrene), any styrene-isoprene-styrene tri-block co-polymer with up to 100% isoprene and up to 50% styrene; unsaturated dienes, their co-polymers and partially or fully crosslinked versions of these same; and an aliphatic polymethane with polydimethyl siloxane backbone. Note that for bondability of such polymers, one or more functional groups may be chemically added to the polymer structure. In particular,balloon4420 may include one or more of a silicone rubber, a Kraton™, and a styrene-isoprene-styrene tri-block co-polymer treated with one or more of the following additives: thiuram disulfide derivatives (R′R″N—(C=5)—S—S—(C=5)—NR′R″), mercaptobenzothiazoles, amino-mercaptobenzothrazole (e.g, such as to vulcanized a silicone rubber), sulfides, and azides. Therefore, for example,balloon4420 may include any of the materials listed above, and may be treated with an additive such as by treating balloonouter diameter4428 with one or more of the additives mentioned above.
• Finally, in accordance with embodiments,outer diameter4428 ofballoon4420 may be bonded to an inner diameter of a plurality of fused layers of ePTFE. For example,FIG. 45 is a cross-section view of a cannula and a lined ePTFE balloon.FIG. 45 showsballoon4520 having a plurality of fused layers ofePTFE4510 withinner diameter4538 of the ePTFE layers bonded toouter diameter4428 ofballoon liner4420. According to embodiments,balloon liner4420 described below as a liner forballoon4520 may beballoon4420 described above forFIG. 44, or any ofballoons308,314,510,2112,2204,2250,2547,2647,3047,3147,3522,3604,3704,3804,3947,4004,4520,4820,8810,9510,9110,9210,9310,9910,9920, as described herein.
• According to embodiments,balloon4520 may have a property such that when inflatedballoon4520 will expand in size to an outer diameter sufficient for occlusion of a blood vessel at an inflation pressure (and/or at an inflation volume as described herein with respect toballoon8810 and/orapparatus9700 or9800 ofFIGS. 75A-81) and less than sufficient to cause an axial force on an inner diameter of the blood vessel. For instance,FIG. 45 showsballoon4520 inflated to outer diameter D2 sufficient for occlusion ofblood vessel4490 at inflation pressure PR, which is a pressure less than sufficient to cause an axial force, such as a force indirections4487, oninner diameter4492 ofblood vessel4490. Note that according to embodiments, a pressure less than sufficient to cause an axial force, includes a pressure less than sufficient to cause an axial force of more than 25 percent of the radial pressure caused by a balloon on the inner diameter of a blood vessel.
• More particularly,balloon4520 may include a property such that when inflated to volume V2,balloon4520 will expand in size to outer diameter D2 that is approximately inner diameter DV ofblood vessel4490 at inflation pressure PR, which is a pressure less than sufficient to exert an axial strain onblood vessel4490 indirections4487. Thus,balloon4520 may be a high-compliance and/or low-tension balloon, such as a balloon that expands radially and longitudinally upon inflation and/or forms a plurality of radial outer diameters during inflation and deflation, but does not form wings. In addition, according to embodiments, pressure PR may be a pressure sufficient to causeballoon4520 to occlude the blood vessel without radially expanding the blood vessel.
• In addition, in accordance with embodiments, fused layers ofePTFE4510 may include one or more layers of ePTFE windings. For example, fused layers ofePTFE4510 may include one or more layers of ePTFE windings wound over each other in concentric, overlaying, intersecting, or criss-cross patterns, wound according to a process, such as is described below with respect toFIG. 46. Specifically, an ePTFE winding may be one or more strips or ribbons of ePTFE material greater in length than in width, where the width of the material is less than or equal to the distance betweenproximal coupling4422 anddistal coupling4424 as shown inFIG. 45. Thus, windings of ePTFE material may be supplied from spools, such as spools for storing or supplying ribbon, cloth material, or tape. Also, it is contemplated that fused layers ofePTFE4510, and/or windings of ePTFE material may be porous and/or may include a property such that the layers or windings of ePTFE do not stretch or have a limited ability to stretch axially, or with respect to the width of the fused layers of ePTFE or ePTFE windings. Thus, during inflation and/or deflation,balloon4520 may include a property such that fused layers ofePTFE4510 expand and contract radially but have no substantial expansion or contraction axially. Note that according to embodiments, no substantial expansion or contraction axially, includes not expanding or contracting axially in length by a distance of more than 5 percent of the outer diameter distance of the layers. For example, fused layers ofePTFE4510 may expand and retract indirections4489 but have no substantial expansion axially indirections4487 as shown inFIG. 45. Moreover, for the embodiment shown inFIG. 45, it is contemplated thatballoon liner4420 may expand and contract axially indirections4487 as well as radially indirections4489.
• Thus, according to embodiments,balloon4520 may have a property to causeballoon4520 to have a post-inflation deflated outer diameter that retracts to within 20% of a pre-inflated outer diameter ofballoon4520. Specifically,balloon liner4420 may causeballoon4520 to retract when deflated to a post-inflated deflated outer diameter DP that is approximately 440% greater than the pre-inflated outer diameter DM ofballoon4520. Moreover,balloon4520 may include a property such that during inflation outerradial surface4528 ofballoon4520 is parallel to the axis ofcannula4410, andsurface4528 expands radially indirections4489 but has no substantial expansion axially indirections4487, or along a direction parallel to the axis ofcannula4410.
• Similarly to balloon4420 ofFIG. 44, fused layers ofePTFE4510 may include a property such that during inflation and deflation, fused layers ofePTFE4510 form a plurality of radial outer diameters, such as diameters DM, D2, and DP, but do not form wings. Also,balloon4420 and/orballoon4520 may include a property such that inflated outer diameter D2 approximates an inner diameter of a coronary sinus of a subject at a region of interest and may be sufficient in diameter to make a pressure waveform of fluid in a coronary sinus or blood vessel become ventricularized. Specifically,balloon4420 and/orballoon4520 may have an outer diameter D2 sufficient to makepressure waveform4486 of fluid4480 inblood vessel4490 become ventricularized. It is also contemplated that diameter D2 may be a diameter sufficient to expand an inner diameter of a blood vessel without damaging or bursting the blood vessel. In other embodiments, inflated outer diameter D2 ofballoon4420 and/orballoon4520 may expand inner diameter DV ofblood vessel4490 sufficient to increase the permeability of a wall ofblood vessel4490 to a treatment or biological agent infused into the blood vessel proximate or super-adjacent to the balloon (e.g., such as a treatment agent described herein, infused at region of interest4496).
• In embodiments,balloon4520 may have a pre-inflated outer diameter between three mm and five mm at a pressure of between zero and one atmosphere (e.g., such as approximately zero atmospheres), and a balloon inflated outer diameter D2 between seven mm and eleven mm inflation pressure PR, of between six and eight atmospheres. Embodiments ofballoon4520 also include a balloon having inflated outer diameter D2 in a range of between five mm and nine mm in diameter at a pressure of less than six atmospheres.
• Likewise, according to embodiments,balloon4420, and/orballoon4520 may have an outside diameter growth rate such as that shown inFIG. 55. Specifically, for an inflation pressure between two and six atmospheres,balloon4420 and/orballoon4520 may include a property such that the balloon will inflate to increase in outer diameter by at least 15% in diameter as compared to a prior outer diameter, for each one atmosphere increase in inflation pressure. Notably, the semi-linear relationship between outer diameter and inflation pressure as shown inFIG. 55 forballoon4420 and/orballoon4520 allows a balloon to be calibrated to determine an amount or volume of liquid, such as volumes V1 or V2, for providing a desired inflation pressure, such as pressure PR. Thus, once a calibration curve of inflation volume versus inflation pressure for a balloon for various inflation volumes of liquid is created, it is possible to select a desired inflation pressure and determine the amount or volume of liquid required to provide that desired pressure. Then, the balloon may be inserted into a subject, such as via percutaneous insertion as described herein, and filled with the predetermined volume of fluid to provide the desired inflation pressure. Therefore, the various configurations ofballoon4420 and/orballoon4520 described herein can be used to occlude a blood vessel, such as an artery or vein in the human heart as is described herein. Furthermore, according to embodiments,cannula4410 ofFIGS. 44 and 45 may be a guide catheter, a delivery catheter, and/or a guidewire, such as described herein.
• In addition, according to embodiments, various appropriate processes may be used to form a lined ePTFE balloon or an ePTFE composite balloon, such asballoon4520. For example,FIG. 46 is a flow diagram of a process for forming a lined ePTFE balloon. Atblock4610, a balloon liner is formed, such as by formingballoon4420 as described above.
• Atblock4620, layers of ePTFE are wound onto a large mandrel, such as by wrapping ePTFE windings, as described above, around a mandrel having a diameter in a range of between 10 mm and 12 mm in diameter. According to embodiments, the diameter of the large mandrel may be selected to be a diameter that is in a range between one mm and two mm larger than the desired diameter of the lined ePTFE balloon when inflated. Specifically, for example, a 10 mm diameter large mandrel may be used when forming a lined ePTFE balloon, such asballoon4520, to have an inflated diameter D2 of 9 mm. Likewise, a mandrel of 11 mm may be used to produce a lined ePTFE balloon having an inflated diameter of 12 mm.
• In addition, according to embodiments, the layers of ePTFE may be formed by ePTFE windings, strips, or ribbons, such as those described above for fused layers ofePTFE4510. For instance, windings of ePTFE material may be wound onto a large mandrel to form multiple layers of ePTFE that overlay, intersect, are concentric with, or criss-cross other windings and/or layers of ePTFE in various patterns and at various angles. Thus, fused layers ofePTFE4510 may include one layer of ePTFE windings wound over another layer of ePTFE windings such that the one layer of windings forms an “X” pattern, a “W” pattern, a “S” pattern, and/or a criss-cross pattern. For example,FIG. 47 is an elevated cut-away view of layers of ePTFE windings. As shown inFIG. 47,first ePTFE windings4710 and4712 are wound oversecond ePTFE windings4720 and4722, such thatfirst ePTFE windings4710 and4712 are at an angle, as shown by angle N of between 30° and 120° with respect tosecond ePTFE windings4720 and4722. Specifically, inFIG. 47, angle N is 90°. However, it is contemplated that angle N may be various other angles between 30° and 120° such as, an angle of 35°, an angle of 45°, an angle of 60°, an angle of 90°, or an angle of 115°.
• Besides winding ePTFE windings in various patterns to form ePTFE layers, various numbers of ePTFE layers may be wound or formed as necessary to ensure that there are enough layers to ensure that the ePTFE layers or windings do not come apart or separate (e.g., such as during inflation and deflation), but not so many ePTFE windings or layers that expansion is inhibited beyond a desired inflation diameter of expansion. For instance, when forming plurality of fusedePTFE layers4510, a sufficient number of ePTFE layers may be wound or formed such that whenballoon4520 is completed, fusedePTFE layers4510 do not separate whenePTFE balloon4520 is inflated to inflation pressure PR of between 6 and 8 atmospheres in pressure. More particularly, as shown inFIG. 47, a first ePTFE layer havingfirst ePTFE windings4710 and4712 may be formed over a second ePTFE layer havingsecond ePTFE windings4720 and4722 to formballoon4520 such that whenballoon4520 is inflatedfirst ePTFE windings4710 and4712 do not separate fromsecond ePTFE windings4720 and4722. Moreover, according to embodiments, sufficient ePTFE layers and windings may be provided so that ePTFE layers and/or windings do not separate along seams, such asseam4730 betweenfirst ePTFE windings4710 and4712. AlthoughFIG. 47 shows only two ePTFE layers, it is contemplated that fusedePTFE layers4510 may include more than two layers, such as by including three layers, four layers, five layers, six layers, seven layers, or10 layers. Thus, for instance, block4620 may include windings between two and six ePTFE layers in a single direction in a “bandage” wrapped style so that seams between ePTFE windings in a single layer are bonded or super-adjacent to each other.
• Atblock4630, layers and/or windings of ePTFE, such as fromblock4620, are fused together, such as by heating the layers and/or windings wound onto the large mandrel. For instance, layers of ePTFE wound onto a large mandrel may be heated at a temperature between 350° C. and 400° C. for a duration of greater than 10 minutes and less than 60 minutes, as necessary to sinter the plurality of ePTFE layers and/or windings. Thus, plurality of fusedePTFE windings4510 may include windings such asfirst windings4710 and4712 wound oversecond windings4720 and4722 onto a large mandrel and heated to a temperature of approximately 380° C. for a duration of between 20 and 30 minutes so as to fusefirst windings4710 and4712 to each other and tosecond windings4720 and4722. After fusing, fused ePTFE layers may be removed from the large mandrel.
• Atblock4640, the fused layers of ePTFE are stretched onto a small mandrel. For instance, a small mandrel may be placed within an inner diameter of the fused ePTFE layers and the fused ePTFE layers may then be stretch apart along the axis of the small mandrel sufficiently so that the ePTFE layers are stretched onto, touch, or conform to the small mandrel. Thus, a distal end and a proximate end of the fused ePTFE layers may be gripped or connected to and stretched apart in opposite directions until the fused layers of ePTFE are stretched sufficiently as described above. After the fused layers are sufficiently stretched, they may be stabilized by heating. For example, the layers may be stabilized over a set temperature and time, such as by heating to a temperature of 380° C. for a duration of between 30 seconds and two minutes in duration (e.g., such as for approximately one minute). Moreover, according to embodiments, the outer diameter of the small mandrel may be selected to be a diameter in a range of between two mm and three mm larger than the desired deflated diameter of a lined ePTFE balloon prior to inflation. For example, the small mandrel may have an outer diameter between two and three mm larger than deflated diameter DM ofballoon4520.
• Atblock4650, the stretched fused layers of ePTFE are compacted axially, such as by being compacted in directions opposite ofdirections4487. For instance, fused layers of ePTFE stretched onto a small mandrel may then have their outer diameter wrapped with a TEFLON™ tape, a “plumbers” tape, or maybe constrained with a steel tube. Then the wrapped or constrained layers of ePTFE may be compacted axially so that the wrapping or constraining of their outer diameter controls expansion of the outer diameter during compacting. For instance, according to embodiments, compacting includes sufficiently compacting axially inwards (e.g., such as in directions opposite of directions4487) a distal end and a proximate end of the stretched fused layers of ePTFE, such that during inflation of the lined ePTFE balloon (e.g., such as during inflation ofballoon4520 to inflation pressure PR), the compacted stretched fused layers of ePTFE (e.g., such as fused ePTFE layers4510) may not expand axially (e.g., such as by being incapable of expanding in directions4487). Moreover, according to embodiments compacting may include sufficiently compacting axially inwards a distal end and a proximate end of the compacted stretched fuses of ePTFE such that during inflation of the lined ePTFE balloon (e.g., such as described above) the compacted stretched fused layers of ePTFE (e.g., such as fused ePTFE layers4510) may expand axially (e.g., such as in directions4487) by a selected percentage of an axial size of the compacted stretched fused layers of ePTFE, during inflation of the lined ePTFE balloon. Hence, more particularly, the stretched fused layers of ePTFE may be compacted sufficiently atblock4650 so that during inflation ofballoon4520, fusedePTFE layers4510 may expand axially indirections4487 by a selected percentage of the length of the compacted stretched fused layers of ePTFE along the longitudinal axis of the small mandrel.
• Furthermore, according to embodiments, compacting may include compacting sufficiently to reduce the porosity of the windings or layers of ePTFE. After compacting, it is contemplated that the compacted stretched fused layers of ePTFE be stabilized over a set temperature and time, such as is described above for stabilizing the fused stretched layers of ePTFE with respect to block4640. After stabilizing the TEFLON™ tape, “plumbers” tape, or tube may be removed from the ePTFE layers and the ePTFE layers may be removed from the small mandrel.
• Moreover, it is contemplated that the large mandrel and/or small mandrel associated withblocks4620 and4640 may be tapered so that the lined ePTFE balloon formed has a tapered profile, such that when inflated, the balloon with expand in size to a first outer diameter at a first position and a different second outer diameter at a different second position. Thus, the large mandrel and the small mandrel may be selected to have a tapered profile so that ePTFE layers have a tapered profile and form linedePTFE balloon4520 that when inflated will expand in size to a first outer diameter at firstaxial distance4432 fromdistal end4414 of the cannula and will expand in size to a different second outer diameter at different secondaxial distance4434 fromdistal end4414 of the cannula, such as to provide a tapered profile similar to that shown inFIG. 39.
• Atblock4660, the layers of ePTFE may be bonded to a balloon liner to form a lined ePTFE balloon, such asballoon4520. It can be appreciated that an inner diameter of the compacted stretched fused layers of ePTFE may be chemically modified prior to bonding to a balloon liner. Specifically,inner diameter4538 ofePTFE layers4510 may be modified with a plasma polymerization of acrylic acid and/or a chemical etch of sodium naphthalene prior to being bonded toballoon4420. Moreover, it is considered that bonding may include vulcanizing an inner diameter of the compacted stretched fused layers of ePTFE to a liner having an outer diameter of silicone rubber material. Also, according to embodiments, bonding may include hydrogen bonding an inner diameter of the compacted stretched fused layers of ePTFE with a balloon liner having an outer diameter of polyurethane material.
• Likewise, in embodiments, bonding may include bonding an inner diameter of the compacted stretched fused layers of ePTFE with a balloon liner having an outer diameter of material such as materials described above for formingballoon4420 and/or treated of modified with additives, such as additives described above with respect toballoon4420. Specifically, chemical modifications to an outer diameter of a balloon liner, such asballoon4420, are considered prior to bonding the balloon liner to the compacted stretched fused layers of ePTFE.
• According to one embodiment, the bonding atblock4660 may include inserting a balloon liner, such asballoon4420, into the inner diameter of the compacted stretched fused layers of ePTFE, such as intoinner diameter4538 of fused layers ofePTFE4510. Then, the outer diameter of the compacted stretched fused layers of ePTFE, such asouter diameter4528 may be constrained with, for example, a TEFLON™ tape, a “plumbers” tape, and/or a steel tube. Next, the balloon liner, such asballoon4420, may be inflated to cause an outer diameter of the balloon liner, such asouter diameter4428, to contact or bond to the inner diameter of the constrained compacted stretched fused layers of ePTFE, such asinner diameter4538. For example, the balloon liner may be inflated to an inflation pressure of between 10 and 50 psi, such as to approximately 30 psi. Next, it is contemplated that the constrained compacted stretched fused layers of ePTFE, such as layers ofePTFE4510, may be heated sufficiently to bond the outer diameter of the balloon liner, such asouter diameter4428, to the inner diameter of the compacted stretched fused layers of ePTFE, such asinner diameter4538. For example, the layers of ePTFE may be heated such as described with respect to stabilizing the layers of ePTFE with respect to block4640.
• After bonding the liner to the layers of ePTFE, the constraining tape and/or steel tube can be removed and the resulting lined ePTFE balloon can be attached to a cannula. For example, atblock4670, linedePTFE balloon4520 may be attached tocannula4410 such as by methods for attaching occlusion devices to a cannula as described herein. Specifically,proximal end4422 and/ordistal end4424 ofballoon4420 and/orballoon4520 may be attached tocannula4410 using one of an adhesive, a crimping bond, a laser bond, and a heat bond, such as to bondproximal end4422 and/ordistal end4422 to surface4416 ofcannula4410. Moreover, it is contemplated that such bonding may include ultraviolet (UV) light adhesive or UV thermal bonding. Finally, it is considered, thatcannula4410 may be a cannula described herein, such as including a guide catheter, delivery catheter, or guidewire.
• Also, in embodiments, occlusion orfilter devices720,2006,2104,4108,4304 as described herein;balloons308,314,510,2112,2204,2250,2547,2647,3047,3147,3522,3604,3704,3804,3947,4004,4420,4520,4820,8810,9510,9110,9210,9310,9910,9920 as described herein; and any other catheter, cannula, tube, sheath, balloon or occlusion device, as described herein may be formed of material including a polymer material, such as a polyurethane-silicone blend (e.g., for example, PurSil™), a homopolymer of an olefin, and/or a co-polymer of an olefin and one or more other material(s). In one embodiment, a filter device, catheter, cannula, tube, sheath, or balloon or occlusion device, as described herein, may have a coating applied to its inside and/or outside surface, such as, for example, a hydrophilic coating.
• Additionally, in one embodiment, a filter device, catheter, cannula, tube, sheath, balloon or occlusion device, as described herein, may be made of or include a material that minimizes allergic reactions and/or provides improved control of expansion outer diameter during inflation and deflation. For instance, such a balloon can be used in a vessel having a diameter range of about four mm to about nine mm diameter. Moreover, such a filter device, balloon, or occlusion device may be designed and/or formed to have a larger distal outer diameter and a smaller proximal outer diameter when inflated (e.g., be thicker distally in outer diameter when inflated and thinner proximally). Specifically, such a filter device, balloon, or occlusion device may have a conical shape.
• In one embodiment, a balloon as mentioned herein may be placed in a blood vessel, such as the coronary sinus or a cardiac vein. For example, a balloon as described herein can be advanced to a location in the great cardiac vein, a branch of the great cardiac vein, the middle cardiac vein, the small cardiac vein, or a coronary artery. Thus, the coronary sinus or the cardiac vein may be elastic in nature, so the balloon may prevent vessel hematomas or occlusion of adjacent coronary artery by functioning as a sealer, and not a dilator. In one embodiment, the balloon is very compliant, achieving occlusion at low pressure for a range of vessel sizes. For example, a diameter of the coronary sinus may range from about 6.5 mm to about 11 mm, a diameter of the great cardiac vein may range from about 4.0 mm to about 7.5 mm, and the diameter of a branch of the great cardiac vein may range from about 2.5 mm to about 5.0 mm.
• It is also considered that a balloon as described herein may be placed in a blood vessel, such as the coronary sinus or a cardiac vein. For example, a balloon described herein may be advanced to a location in the great cardiac vein, a branch of the great cardiac vein, the middle cardiac vein, or the small cardiac vein, or a coronary artery to occlude the vessel prior to the infusion or retro-infusion of a fluid or treatment agent. In this embodiment, the balloon is able to extend if the vessel is enlarged during the infusion or retro-infusion and maintain occlusion of the vessel.
• In some embodiments, a balloon as described herein may be made from or include material such as a polyether block amide, a polyetheramide, and mixtures thereof. Similarly, a balloon as described herein may be made from or include a polymer having a structure of a regular linear chain of rigid polyamide segments interspaced with flexible polyether segments. In an embodiment, a balloon as described herein may be made from or include a polymer or a mixture of two or more of the polymers having the tradename PEBAX® (a registered trademark of ATOCHEM), for example Pebax 63D and 55D, or for example one or more PEBAX® polymers having a Shore D hardness less than 70D. In an embodiment, a balloon as described herein, such as for occluding a blood vessel may be made from or include a polymer or a mixture of two or more of the polymers represented by the formula:

  

  
  (Where PA represents a polyamide segment, and PEth represents a polyether segment, and “n” represents an integer of at least one.)
• In an embodiment, a balloon as described herein to be inflated to a selected inflation pressure and/or volume may occlude a blood vessel at a pressure of about 0.5 to about five atmospheres. In another embodiment, a balloon may achieve a growth rate greater than about 40% while maintaining a pressure below four atmospheres or even below one atmosphere. Here, the balloon pressure is kept low despite an increase in diameter because of the elasticity of the balloon material. In an embodiment, the balloon may have an expanded outer diameter between about 1.5 millimeters (mm) and about 18 mm when inflated. Moreover, the balloon may have a double wall thickness between about 0.0003 and about 0.0038 inches and/or a minimum hoop strength of at least about 23,000 pounds per square inch (psi). In another embodiment, the balloon may be either heat bonded, laser bonded, shrink tube or wrap bonded, or attached with an adhesive to a catheter, cannula, port, lumen, and/or tube as described herein.
• In some embodiments, a balloon or occlusion device, as described herein may be a high compliance low pressure balloon. For example,FIG. 48 is a cross section view of a cannula and a high compliance low pressure balloon. As shown inFIG. 48, cannula4810 (e.g., such as a cannula having a dimension suitable for percutaneous advancement through a blood vessel, such as advancement indirection4885 through blood vessel4890), includesproximal end4812,distal end4814, andexterior surface4816.FIG. 48 also showsballoon4820 axially connected toexterior surface4816 ofcannula4810, at or adjacentdistal end4814.FIG. 48 shows cannula4810 having diameter of cannula DC, andballoon4820 having minimal wing diameter DM, and balloon outer first diameter D1.Blood vessel4890 is shown having diameter of vessel DV and fluid4880 (e.g., such as blood and/or treatment agent).Balloon4820 may be a balloon, occlusion device, or filter device such as described herein.
• Furthermore, according to embodiments,balloon4820 may include material or matter having a polymer moiety represented by the formula

  

  
  wherein PA represents a polyamide moiety, and PEth represents a polyether moiety, and “n” represents an integer of at least one. In addition, according to embodiments,balloon4820 may include a thermoplastic blend copolymer material having one of a polyether block amide resin moiety and a polyetheramide moiety. In addition, according to embodiments,balloon4820 may be restricted or restrained from expansion or inflation, such as by a sheath (e.g., such assheath790 described above forFIGS. 7-10), to have first diameter D1.
• According to embodiments,balloon4820 may have a property such thatballoon4820 will inflate, such as indirections4886 and4888 as a result ofpressures4830 and4832 increasing balloon first volume V1, to an inflated balloon outer second diameter that will occlude a blood vessel. For example,FIG. 49A is a cross sectional view of a cannula and a balloon inflated to occlude a blood vessel. As shown inFIG. 49A,balloon4820 is inflated to second diameter D2 that will occlude blood vessel4990, such as by substantially preventing fluid4980 from flowing inblood vessel4890past balloon4820 indirection4985. Likewise,FIG. 49A showsballoon4820 inflated to have volume V2, and exert pressure PR on an inner diameter ofblood vessel4890.
• Consequently, according to embodiments,balloon4820 may include a property such thatballoon4820 can achieve a volumetric expansion (e.g., such as by expanding from first volume V1 to second volume V2) of greater than about 40% during inflation. Specifically,balloon4820 may have a property such that it may inflate according to the growth rate chart ofFIG. 55. Moreover,balloon4820 may be able to expand or inflate to an inflated outer diameter, such as second diameter D2, between 1.5 millimeters and 18 millimeters in diameter. Likewise, according to embodiments,balloon4820 may be inflated to second diameter D2 to occludeblood vessel4890 at a predetermined pressure, such as pressure PR, of between 0.5 atmospheres and 5.0 atmospheres of pressure. More particularly,balloon4820 may include a property such that it will inflate to a predetermined pressure, such as pressure PR, sufficient to make a pressure waveform in a blood vessel become ventricularized. For example,balloon4820 may inflate to a predetermined pressure to make a pressure waveform of blood or fluid, such as fluid4980, traveling indirection4985 become ventricularized. Thus,balloon4820 may be inflated to a predetermined volume, such as second volume V2, and/or a predetermined inflated outer diameter, such as second diameter D2.
• Furthermore,balloon4820 may have deflated a double wall thickness between 0.0003 and 0.0038 inches in thickness. For example,FIG. 49B may be a cross sectional view ofFIG. 49A from perspective “A”, according to an embodiment.FIG. 49B shows single wall thickness T ofballoon4820, wherein T is 1/2 of the double wall thickness. Moreover, according to embodiments,balloon4820 may have a minimum hoop strength of at least about 23,000 psi strength. Also,balloon4820 may include a property such that the balloon will have a durometer hardness of between 50 Shore D and 70 Shore D. Next,balloon4820 may be axially connected to an exterior surface of a cannula, such ascannula4810, wherein the cannula may be a guide cannula, a delivery cannula, or a guide wire as described herein.
• FIG. 49B also showscannula4810 havinglumens4912,4914, and4940. Lumen4912 may be a lumen such aslumen1712 described above forFIG. 17.Lumen4914 may be a lumen such aslumen1812 described above forFIG. 18.Lumen4940 may be a lumen such aslumen1740 described above forFIG. 17. It is also considered any of thatlumens4912,4914, and4940 may be similar to a guidewire lumen, accessory lumen or pressure lumen as described herein.
• According to embodiments,balloon4820 may include a property such that the balloon will deflate, such as indirections4986 and4988 as a result ofpressures4930 and4932 to reduce second volume V2, to a post-inflated deflated balloon outer third diameter. For example,FIG. 50 is a cross sectional view of a cannula and a postinflated deflated balloon. As shown inFIG. 50,balloon4820 is postinflated deflated to third volume V3 and third diameter D3. Specifically,balloon4820 may be deflated to third diameter D3 that will allowballoon4820 to be withdrawn from a blood vessel, such as withdrawn indirection4985 fromblood vessel4890. Consequently, postinflated deflated volume ofballoon4820, such as third volume V3 may be approximately equal to preinflated volume ofballoon4820, such as volume V1.
• Furthermore, according to embodiments,balloon4820 may include a property such that it has at least three wings prior to being inflated and after being deflated. For example,FIG. 51 may be a cross sectional view ofFIG. 48 from perspective “A”, according to an embodiment.FIG. 51 showsballoon4820 havingwings4852,4854, and4856 prior toballoon4820 being inflated. Moreover, each wing has a wing length defined by the length of a line extending within the wing along a medial axis of a cross-section of the wing. For example,FIG. 51 showswing4852 having wing length one WL1 defined by the length of a line extending withinwing4852 along a median access of a cross section ofwing4852, such as shown by wing length one WL1 inFIG. 51.
• In addition,balloon4820 includes a property such that the wings ofballoon4820 are subsumed into the outer diameter ofballoon4820 when inflated. For example,FIG. 52 may be a cross sectional view ofFIG. 49A from perspective “A”, according to an embodiment.FIG. 52 showsballoon4820 havingouter balloon diameter5228 when inflated, and second diameter D2 which is approximately equivalent to that of or at least equivalent to that of an inner diameter of a blood vessel at a region of interest. Thus, second diameter D2 may be approximately equivalent to or at least equivalent to diameter of vessel DV ofblood vessel4890. Moreover, according to embodiments, second diameter D2 may be a diameter sufficient to occlude a blood vessel, such asblood vessel4890.
• Further,balloon4820 may include a property such that the balloon will have at least three wings prior to being inflated and after being deflated, wherein a pre-inflated wing length for each wing is approximately equal to a post-inflated deflated wing length for each wing. For example,FIG. 53 may be a cross sectional view ofFIG. 50 from perspective “A”, according to an embodiment.FIG. 53 shows postinflated deflated wing length two WL2 ofwing length4852 being a wing length that is approximately equal to preinflated wing length one WL1. Thus, althoughballoon4820 is shown prior to inflation inFIG. 49A and after being inflated and deflated inFIG. 53, the wing length ofwing4852 prior to inflation is approximately equal to that forwing4852 after being inflated and deflated.
• However, according to embodiments,balloon4820 may include a property such that an outer diameter point farthest away from the access ofcannula4810 for each wing is approximately 30% greater for the postinflated deflated wing than it is for the preinflated wing. For example,FIG. 51 showswing4852 having outer diameter point one P1 defined by a point ofwing4852 radially farthest away from axis of the cannula AC, and wing diameter one DW1 defined by a length of a straight line extending from axis of cannula AC, radially out to the outer diameter point one P1. Similarly,FIG. 53 showswing4852 after being inflated and deflated having outer diameter point two P2 defined by a point of the wing radially farthest away from axis of the cannula AC, and a wing diameter two DW2 defined by a length of a straight line extending from axis of the cannula AC, radially out to outer diameter point two P2. Thus, according to embodiments, preinflated wing diameter DW1 forwing4852 is approximately 30% less than postinflated deflated wing diameter DW2 ofwing4852. Hence, although the wing length for a postinflated deflated wing is approximately equal to that of a preinflated wing, the wing diameter for a postinflated deflated wing may be greater than that for a preinflated wing, such as in a range between 10% and 50% greater in wing diameter.
• Therefore, the various configurations ofballoon4820 andlumen4810 described herein can be used to occlude a blood vessel, such as by using a high compliance low pressure balloon forballoon4820, as described above. For example,FIG. 54 is a flow diagram of a process for using a balloon (e.g., such as any balloon or occlusion device described herein, including embodiments ofballoon4820 described with respect toFIGS. 48-53 and views thereof) to occlude a blood vessel (e.g., such as a process that may be used withsystem controller3080, and/or a treatment process for infusion of a treatment agent into an artery or vein of a patient using devices, apparatus, methods, and/or processes described herein (e.g., such as according to the process described with respect toFIGS. 3, 19,54,55,63, and/or82). At block5410 a cannula, such ascannula4810, is advanced percutaneously through a blood vessel, such asblood vessel4890, wherein a balloon, such asballoon4820, is axially connected to an exterior surface of the cannula at or adjacent the distal end of the cannula. It is contemplated that the cannula may be advanced via a retrograde advancement, such as by being pushed up a blood vessel with or against a flow of blood, such as from one vessel into a smaller vessel to provide retrograde infusion treatment. Specifically, the cannula may be advanced to a region of interest such as a region in a coronary sinus or vein of a subject (e.g., such as region of interest4996).
• At block5420, the balloon is inflated to between 0.5 atmospheres and 5.0 atmospheres of pressure. For example,balloon4820 may be inflated so that first diameter D1 is increased to second diameter D2, as described above. Also, according to embodiments,balloon4820 may be inflated by inflating to an expansion pressure of between two atmospheres in pressure and six atmospheres in pressure applied to an inner diameter of a blood vessel, such as diameter of vessel DV, at a region of interest such asregion4996. Moreover, according to embodiments,balloon4820 may be inflated to a predetermined volume (e.g., such as volume V2), a predetermined second diameter in a range between four millimeters and 17 millimeters in diameter (e.g., such as second diameter D2), and/or a predetermined pressure of between 0.5 atmospheres and six atmospheres in pressure (e.g., such as pressure PR).
• At block5430 the blood vessel is occluded. Specifically,balloon4820 may be inflated to expand first diameter D1 to second diameter D2 until second diameter D2 approximates an inner diameter of a coronary sinus or a coronary blood vessel of a subject at a region of interest and/or until second diameter D2 is sufficient to make a pressure waveform of fluid in the coronary sinus or coronary vein become ventricularized, such as is described herein.
• At block5435 a treatment agent is delivered, such as to a region of interest. For example, a treatment agent may include infusion pellets, suspended cells, stem cells, microspheres, blood cells, drugs, and/or various other appropriate liquids and materials as described herein. Likewise, it is contemplated that such treatment agents may be delivered to region ofinterest4996, such as by being delivered as part of or as all of liquid4980. Note that it is contemplated thatballoon4820 may be inflated and/or deflated using fluids, including fluids described herein as a treatment agent.
• At block5440 the option of aspirating a region of interest is provided. For example, region ofinterest4996 may be aspirated such as by a hole indistal end4814 ofcannula4810 or via a hole throughexterior surface4816 ofcannula4810 atdistal end4814. Specifically, for instance, liquid4980 may be aspirated as described above with respect tohole988 forFIG. 9. Thus, as shown inFIG. 49, liquid4980 in region ofinterest4996 may optionally be aspirated. It is contemplated that liquid4980 may include a drug, treatment agent, infusion pellets, suspended cells, stem cells, microspheres, and/or various other appropriate liquids or materials as mentioned herein.
• At block5450balloon4820 is deflated, such as described herein. For example,balloon4820 may be deflated to a post inflation deflation volume, such as third volume V3, approximately equal to a preinflated volume, such as first volume V1, ofballoon4820.
• At block5460cannula4810 may be retracted, such as to withdrawballoon4820 back out ofvessel4890 and out of the subject.
• FIG. 55, illustrates a balloon outside diameter growth rate, such as for an occlusion or filter device (e.g., includingdevices720,2006,2104,4108,4304 as described herein), a balloon (e.g., such asballoons308,314,510,2112,2204,2250,2547,2647,3047,3147,3522,3604,3704,3804,3947,4004,4420,4520,4820,8810,9510,9110,9210,9310,9910,9920 as described herein), or other balloons or occlusion devices, as described herein). For instance,FIG. 55 may show the outsidediameter growth rate5510 for an eight mm balloon starting with the uninflated outside diameter, and growing to the balloon's inflated outer diameter, where the growth rate is plotted as a function ofinflation pressure5520.FIG. 55 shows a balloon with a growth rate or elasticity of about 25% at a pressure of about two atmospheres. In another embodiment, a balloon may have a growth rate or elasticity of about 40% at a pressure of about 3.5 atmospheres.
• In one embodiment, balloon outer diameter sizing (e.g., such as to occlude a blood vessel with a balloon, as described herein) is controlled by monitoring factors including venous pressure waveform changes distal to the balloon. For instance, inflation of the balloon may be continued until a waveform becomes ventricularized.
• FIG. 56 illustrates a graph showing pressure distal to a balloon6510 in a blood vessel as a function of time6520 (e.g., such as the pressure at region ofinterest996 to be infused with a treatment agent, where the region of interest may be distal to, or proximal to a balloon occluding a blood vessel, as described herein). It is to be appreciated that the process related toFIG. 56 may be a process that may be used with a system controller (e.g., such as a system controller that may access a memory including machine readable instructions, such as system controller3080), and/or a treatment process for infusion of a treatment agent into an artery or vein of a patient using devices, apparatus, methods, and/or processes described herein (e.g., such as according to the process described with respect toFIGS. 3, 19,54,55,63, and/or82). Reference numeral6501 illustrates time t1 during which a catheters and/or cannula as described herein is advance percutaneously so that a distal end of the catheter or cannula can be located in the coronary sinus or another vessel.
• Reference numeral5602 corresponds to time t2 during which a balloon, such as described herein is inflated to occlude the coronary sinus or another blood vessel. The coronary sinus or other blood vessel may be occluded, for example by inflating an occluding balloon or device until the coronary sinus or other blood vessel has a pressure waveform that becomes ventricularized.
• Reference numeral5603, corresponding to time t3 during which a treatment agent, such as described herein, is infused or introduced into the blood vessel and increases the pressure in the vessel to a relatively higher pressure distal to the balloons (and/or at region of interest996).
• At the conclusion of the infusion period, t3, time t4 referred to byreference numeral5604, is a period of time where the pressure distal to the balloon is a lower pressure following infusion, even though the coronary sinus or other vessel is still occluded by a balloons or occlusion device.
• Reference numeral5605, refers to time t5, during which the occluding balloon or device is deflated, and the catheter or cannula may be removed so that the perfusion (e.g., such as according to the process described with respect toFIG. 82) or flow of blood and/or treatment agent can resume in the coronary sinus or another vessel.
• In one embodiment, the plot illustrated inFIG. 56 allows for an efficient treatment agent and/or drug infusion from a vein or artery to tissue to be treated with the possibility of “hands-off” operation. In one embodiment, when the pressure waveform changes to a “ventricularized” waveform of venous pressure, a balloon-sizing indicator notifies the operator or control system to stop balloon inflation. After balloon inflation has been stopped, a pressure sensor can measure the infusion pressure needed for an effective therapeutic dosage of a liquid containing a treatment agent. Infusion of a treatment agent can be accomplished with auto-infusion with a controller (e.g., such as controller3080), or by an operator manually (e.g., such as byapparatus9700 or9800 ofFIGS. 75A-81).
• Suitable treatment agents to be used with catheters and/or cannula as described herein include a liquid carrying one or more treatment agents. In another embodiment, a treatment agent or liquid includes one or more drugs and/or treatment agents, such as is used to prevent reperfusion injury. For instance, according to embodiments, a treatment agent may be or include a liquid having one or more antibodies, for example, the antibodies against CD11/18, P-selectin, L-selectin, ICAM, and/or VCAM. In another embodiment, the liquid includes IGF-I, estrogen, and/or GIK solution. In another embodiment, the liquid includes drugs like adenosine or its isoforms, Na/H exchangers, and/or Na/K exchangers. In another embodiment, the liquid can include cells, for example, cardiomyocites and/or multi-potent or ologo-potent cells like stem cells and/or progenitor cells. Also, the liquid may include angiogenic cells, and/or other types of structural cells like skeletal or smooth muscle cells. In another embodiment the liquid includes biological agents and/or genes, for example, VEGF, FGF, and/or HGF. In another embodiment, liquid includes one or more of the following: Calpain I, insulin, adenosine, antioxidants, glutathione peroxidase, vitamin E (alpha tocopherol), Na⁺-H+exchange inhibitors, caroporide (HOE642), agents that open KATP channels, nitric oxide (NO), endothelin receptor antagonists, tetrahydrobiopterin, statins, sevoflurane, propofol, pinacidil, morphine, verapamil, and blends or mixtures thereof.
• In an embodiment, a pressure increasing device may be attached to fitting2632 atproximal end2626 of catheter2620 (e.g., seeFIGS. 26-29, and fitting3032 atproximal end3026 ofcatheter3020 ofFIG. 30) to deliver a liquid that is or includes a treatment agent, as described herein, through delivery lumen and to a blood vessel, such as at region of interest996 (e.g., such as via a catheter, cannula, or deliver lumen as described herein). In one embodiment, the pressure increasing device is a syringe. In embodiments, the pressure increasing device may be a pump (which may or may not include one or more syringes). For example, the pressure increasing device can be a centrifugal pump, a reciprocating pump, or a gear pump. In one embodiment, the pump is able to achieve a low flow rate at a high pressure. One suitable pump is illustrated inFIG. 57.Centrifugal pump5700 includesinlet5702 andoutlet5704 so that the fluid flows as marked byarrow5706.Pump5700 haspumphousing5708 to contain fluid androtor5710 which hasimpeller5712 attached. In one embodiment,impeller5712 rotates to create a centrifugal force to force fluid frominlet5702 tooutlet5704 as shown byarrow5706.Pump5700 also includesstator5714 which has winding5716 attached. In one embodiment,rotor5710 is removably connected tostator5714, and there is no direct mechanical connection betweenstator5714 androtor5710. In one embodiment,rotor5710 andimpeller5712 are driven by a magnetic force generated by winding5716. In one embodiment,rotor5710 and pumphousing5708 are disposable, whilestator5714 and winding5716 are not disposable. In another embodiment, the fluid flows throughinlet5702 tooutlet5704, which fluid path is sterilized, whilestator5714 and winding5716 are not sterilized. It is considered that a suitable pump can be a disposable infusion pump or a magnetically-levitated centrifugal pump with a disposable rotor chamber.
• In another embodiment, a suitable pressure increasing device is illustrated inFIG. 58.Pump5800 includeshandle5820 withbatteries5809, andactivator button5810. Connected to handle5820 isbody5830 ofpump5800.Body5830 includespressure measurement connection5808,micro-controller5805, andmotor driver chip5812.Pump5800 also includesattachment5832 withmotor5804,motor coupler5803, wherecoupler5803 is connected to leadscrew 5802.Lead screw5802 is fed into non-rotating threadedcoupling5824, so that whenmotor5804 is activated, rotational force and motion frommotor5804 is transferred throughcoupler5803 to leadscrew5802 to advance or retract non-rotating threadedcoupling5824, depending on the direction of rotation. Non-rotating threadedcoupling5824 is attached toplunger5801, so that when non-rotating threadedcoupling5824 moves,plunger5801 also moves.Plunger5801 can move distally to makereservoir5814 smaller, or proximally to makereservoir5814 larger. At the distal end ofreservoir5814 isnozzle5816 attached tooutlet5818.
• In operation, user (not shown) may activatepump5800 by pressingbutton5810.Pressing button5810 causes micro-controller5805 to activate, which in turn activatesmotor driver chip5812 which sends a current frombatteries5809 tomotor5804. This causesmotor5804 to rotate, sending a rotational motion and force throughcoupler5803 to leadscrew 5802. Rotatinglead screw5802 causes non-rotating threaded coupling andplunger5801 to advance or retract, depending on the rotation ofmotor5804 and leadscrew 5802. Advancingplunger5801 causes an increase in pressure and a decrease in volume inreservoir5814 causing fluid or gas stored inreservoir5814 to be forced throughnozzle5816 and intooutlet5818. In one embodiment, to maintain a suitable pressure, pressure feedback from the patient may be received intopump5800 throughpressure measurement connection5808, which pressure information is fed tomicro-controller5805, which activatesmotor driver chip5812, to activatemotor5804 to increase pressure, or to deactivatemotor5804 to allow pressure to drop, or to reverse the direction ofmotor5804 to decrease pressure.
• Another suitable pressure increasing device is illustrated inFIG. 59.Pump5900 includeshandle5920 havingbatteries5909, andactivation button5910.Handle5920 is connected tobody5930, which includespressure measurement connection5908,motor driver chip5912, andmicro-controller5905. Connected tobody5930 isattachment5932 withmotor5904,coupler5903, and leadscrew5902.Lead screw5902 feeds into non-rotating threadedcoupling5924, which is attached to syringe and/or abutted againsthead5940.Syringe5922 is located in a suitably shaped opening, the distal end ofhandle5932, and includessyringe head5940,plunger5901,reservoir5914, andnozzle5916.Nozzle5916 feeds intooutlet5918. In another embodiment,syringe5922 may be disposable and thrown away after each treatment. In another embodiment,syringe5922 may be removed and cleaned and/or sterilized prior to the next treatment. In some embodiments, the pump, such aspump5900 may have multiple syringes with different treatment agents.
• In operation,pump5900 may be activated by a user (not shown) bybutton5910, which activatesmicro-controller5905, which activatesmotor driver chip5912, which in turn activatesmotor5904, by sending a current frombatteries5909 tomotor5904.Motor5904 rotatescoupler5903, which rotateslead screw5902 to advance or retract non-rotating threadedcoupling5924, which serves to advance or retractsyringe head5940, respectively. Ifsyringe head5940 is advanced,plunger5901 is also advanced towards the distal end ofhandle5932 which serves to increase the pressure and decrease the volume ofreservoir5914, which forces fluid or gas stored inreservoir5914 throughnozzle5916 and intooutlet5918. Ifsyringe head5940 is pulled towards proximal end ofhandle5932, then the pressure inreservoir5914 is lowered, and the volume inreservoir5914 is increased, and fluid may be pulled fromoutlet5918 throughnozzle5916 and intoreservoir5914. In one embodiment, a pressure measurement from the patient may be delivered intopump5900 throughpressure measurement connection5908, which information is fed to micro-controller5905 then intomotor driver chip5912 which is used to controlmotor5904 to advance or retractsyringe head5940 to raise or lower pressure inreservoir5914, respectively.
• Referring now toFIG. 60, there is illustrated a suitable pressure transferring device.Pressure transferring device6000 includesfluid inlet6002, andfluid outlet6004.Plunger6006 is located indevice6000, which plunger6006 serves to separateinlet reservoir6008 fromoutlet reservoir6010. As a fluid is pumped intoinlet6002, fluid entersinlet reservoir6008 and exerts a force uponplunger6006. This forcesplunger6006 distally, which increases the pressure and lowers the volume ofoutlet reservoir6010, which forces the fluid inoutlet reservoir6010 intooutlet6004. Conversely, when a fluid is forced intooutlet6004 and intooutlet reservoir6010, it exerts a force onplunger6006, and forces plunger6006 proximally, which increases the pressure and lowers the volume ofinlet reservoir6008 and forces the fluid ininlet reservoir6008 intoinlet6002.Device6000 serves to equalize the pressures ininlet6002 andinlet reservoir6008, with the pressures inoutlet6004 andoutlet reservoir6010.Device6000 may be used immediately before a catheter, so that a relatively expensive treatment agent can be placed inoutlet reservoir6010 andoutlet6004, while a relatively inexpensive liquid, for example a saline solution or water, can be placed ininlet reservoir6008 andinlet6002, with a pump (not shown) or other pressure increasing device connected toinlet6002.
• Referring now toFIG. 61, is a pressure-maintaining or dampeningdevice6100.Device6100 hasinlet6102 andoutlet6104. Insidedevice6100 is plunger6106 which serves to seal fluid intopressure reservoir6112. As fluid flows frominlet6102 intopressure reservoir6112, the fluid exerts a force onplunger6106 which compressesspring6108, until the force exerted byspring6108 equals the force exerted by the fluid inpressure reservoir6112 onplunger6106. When the fluid stops flowing frominlet6102 intopressure reservoir6112, there will be a fluid flow provided tooutlet6104 asplunger6106 is forced down bycompressed spring6108, decreasing the size offluid reservoir6112. This downward movement ofplunger6106 continues until pressure inpressure reservoir6112 equals downward pressure exerted byspring6108. In another embodiment,spring adjusting device6110 may be provided to adjust the tension ofspring6108, so that more or less force is required to compressspring6108.
• Referring now toFIG. 62, is a pressure-maintaining or dampeningdevice6200, withinlet6202 andoutlet6204. As fluid flows throughinlet6202 and intopressure reservoir6212, the fluid causesreservoir6212 to forcewalls6208 ofdevice6200 outwards until the inward force exerted bywalls6208 equals the outward force exerted by fluid inpressure reservoir6212. When the fluid flow throughinlet6202 stops, fluid flow tooutlet6204 continues until force exerted bywalls6208 equals force exerted by fluid inpressure reservoir6212.Walls6208 may be made of a flexible material, for example rubber. Materials and thickness ofwalls6208 may be adjusted so that an appropriate pressure may be maintained withinfluid reservoir6212.
• Referring now toFIG. 63, is a flow diagram of a process or method of treating a patient, in accordance with an embodiment. First, a vein is accessed6302 by a catheter, for example, the exterior femoral vein, the interior femoral vein, carotid, jugular, brachial, subclavian, or saphalic vein is accessed by distal end of a guide catheter.Coronary sinus6304 is accessed with a guide catheter through either the inferior vena cava or superior vena cava.Venogram6306 is performed through the guide catheter to visualize coronary sinus and/or great cardiac vein. Deployment of guidewire andretroinfusion balloon catheter6308 into the coronary sinus through the guide catheter.Venogram6310 to visualize distal venus anatomy. Navigation of infusion catheter overguidewire6312 to a target location. Measurement ofbaseline parameters6314, for example, pressure, flow, oxygen saturation, pH, and/or temperature at the target location. Inflateballoon6316 to occlude coronary sinus and/or other vessel where balloon catheter has been placed, for example the target location. Performblush score6318, an optional step to determine blush pressure. Setinfusion parameters6320, for example, absolute pressure, differential pressure, blush pressure, dosage, and/or flow rate.Start infusion6322. Optional measuring of infusion parameters and feedback to a controller.Stop infusion6324 when set parameters are satisfied. Hold balloon inflated6326 for a period of time to allow uptake and/or saturation.Deflate balloon6328. Remove catheter, guide catheter and/or guidewire, fromvessel6330.
• Note that it is contemplated that the process described above with respect toFIG. 63, any or all of the pressure increasing devices, pumps, pressure transfer devices, and/or pressure maintaing devices described herein may be controlled manually, automatically, and/or by a machine, such as bysystem controller3080, and/or according to a treatment process for infusion of a treatment agent into an artery or vein of a patient using devices, apparatus, methods, and/or processes described herein (e.g., such as according to the process described with respect toFIGS. 3, 19,54,55, and/or82).
• In another embodiment, a catheter may be used to locally administer a treatment or therapeutic agent. Copending U.S. Application having Ser. No. 10/246,249 filed on Sep. 18, 2002 discloses suitable treatment agents and suitable methods of administering the treatment agents. Copending U.S. Application having Ser. No. 10/246,249 filed on Sep. 18, 2002 is herein incorporated by reference in its entirety. U.S. Pat. No. 6,346,098, issued to Yock et al., discloses a suitable method of locally administering a treatment agent. U.S. Pat. No. 6,346,098, issued to Yock et al., is herein incorporated by reference in its entirety.
• Note that all embodiments of devices, apparatus, methods, and/or processes described herein are contemplated to include treatment including by one or more balloons, occlusion devices, and/or filter devices (e.g., such asballoon2647,3147,3522,3947,2547,3047,3604,3704,3804,4004,308,2204,2250,2112,314,510,4420,4520,4620,4820,8810,9510,9110,9210,9310,9910,9920, or other balloons or occlusion devices, as described herein) that may have an outer diameter that is volume controlled (e.g., see balloon8810) and/or pressure controlled (e.g., seeballoons4520,4620, and4820) to expand to, occlude, and/or filter fluid in a blood vessel (e.g., such as an artery or vein of a human being). For example, an outer diameter may be volume controlled by controlling the amount of inflation volume of a gas (e.g., such as air, carbon dioxide, or a gas having a fluoroscopy contrast agent) or a liquid (e.g., such as water, saline solution, or a fluid having a fluoroscopy contrast agent) used to inflate the occlusion device. Specifically, an inflation volume may be incrementally increased by a selected volume amount over a range of total inflation volume to cause the outer diameter of an occlusion balloon to incrementally increase by a predictable amount for each incremental increase in volume. Thus, equal or unequal incremental increases in inflation volume can be used to cause equal or unequal increases in occlusion device outer diameter, over a desired total diameter range.
• For instance, according to embodiments, additional inflation fluid volume does not increase pressure because the high compliance balloon grows in outer diameter. Furthermore, according to embodiments, when the outer diameter reaches a constraint, such as the inner diameter of a blood vessel as described herein, the balloon has a property, dimension, and/or is configured such that additional inflation fluid volume does not increase pressure or force in a direction perpendicular to the outer diameter (e.g., such as in a direction towards the inner diameter of the blood vessel), because the high compliance balloon grows in an axial direction within the blood vessel. It is also contemplated that when the outer diameter of the balloon reaches a constraint, additional inflation fluid volume will increase pressure or force in a direction perpendicular to the outer diameter of the balloon, but not appreciably. Specifically, in accordance with an embodiment, additional inflation fluid volume will increase pressure or force in a direction perpendicular to the outer diameter of the balloon by a non appreciable amount, such as by between zero and 10 percent increase in pressure (e.g., where the pressure in a direction perpendicular to the outer diameter of the balloon may be equal to the inflation pressure withing the balloon).
• For example,FIG. 64A is a cross sectional view of a cannula and a balloon.FIG. 64A showsapparatus8800 havingcannula8802 with a dimension suitable for percutaneous advancement through a blood vessel (e.g., such asblood vessel990 mentioned herein) and having a cannula proximal end (not shown, but such asproximal end9504 shown and described with respect to FIGS.69A-F) anddistal end8806.FIG. 64B is a cross-sectional view ofapparatus8800 ofFIG. 64A from perspective “A”.Cannula8802 may be a cannula similar tocannula710 or any other catheter or cannula, as described herein.FIGS. 64A and B also show cannula8802 having diameter CRD such as a diameter for a guide catheter, delivery catheter, or guidewire catheter as described herein.Balloon8810 is axially attached toexterior surface8808 at or adjacentdistal end8806 ofcannula8802 atproximal attachment8809 anddistal attachment8811.Balloon8810 may be a balloon such as a balloon or occlusion device as described herein.
• According to embodiments,balloon8810 may have a property such that when inflated to a plurality of selected increasing inflation volumes,balloon8810 forms a plurality of predictably increasing radial outer diameters, and has an inflation pressure that increases by less than five percent in pressure while being inflated to the plurality of selected increasing inflation volumes.
• Moreover,balloon8810 may be is adapted to inflate to an outer diameter in a range of about 2 mm to about 20 mm, such as to occlude a blood vessel having an inner diameter in a range of between 1.5 mm and 19.5 mm. Specifically,balloon8810 may selected and/or inflated by a sufficient inflation volume or pressure to inflate to an outer diameter approximately 0.5 mm greater than the inner diameter of the blood vessel it is to occlude. Thus,balloon8810 may inflate to an outer diameter of about 2 mm to occlude a blood vessel having an inner diameter of about 1.5 mm, and may inflate to an outer diamter of about 20 mm to occlude a blood vessel having an inner diameter of about 19.5 mm.
• Also shown inFIGS. 64A and B,balloon8810 has first diameter BRD1, first length BRL1, first inflation volume BRV1 and first inflation pressure BRP1. According to embodiments first length BRL1 may be a selected preinflated length greater than two millimeters in length, such as a length of between two millimeters and 30 millimeters, (e.g., including first length BRL1 equal to three millimeters, between five and six millimeters, between eight and 10 millimeters, between five and 10 millimeters, or greater than 30 millimeters in length). In addition, first diameter BRD1 may be a preinflated outer diameter of between 0.25 inches and 0.65 inches in diameter (e.g., such as first diameter BRD1 of 0.44 inches) that inflates to expand to an outer diameter of 18 millimeter when inflated without bursting or permanently deforming. Next,balloon8810 may have a preinflated single wall thickness of between 0.001 inches and 0.02 inches in thickness (e.g., such as a wall thickness of 0.003 inches) at a preinflation pressure below one atmosphere in pressure, such as a preinflation pressure of zero atmosphere.
• FIG. 65A shows the balloon and cannula ofFIG. 64A, with the balloon inflated to a second inflation volume.FIG. 65B is a cross-sectional view ofapparatus8800 ofFIG. 65A from perspective “A”.FIGS. 65A andB show balloon8810 inflated to second inflation volume BRV2, second inflation pressure BRP2, second length BRL2, and second diameter BRD2. For example, second inflation volume BRV2 may be one of a plurality of selected increasing inflation volumes to causeballoon8810 to form a second predictably increasing radial outer diameter, second diameter BRD2, and to have a second inflation pressure, BRP2 that may or may not be less than five percent greater than first inflation pressure BRP1.
• FIG. 66A shows the cannula and balloon ofFIG. 65A, with the balloon inflated to a third inflation volume.FIG. 66B is a cross-sectional view ofapparatus8800 ofFIG. 66A from perspective “A”.Balloon8810 is inflated to third inflation volume BRV3, third inflation pressure BRP3, third length BRL3, and third diameter BRD3. For example,FIGS. 66A andB show balloon8810 inflated to a selected increasing third inflation volume BRV3 to form predictably increasing radial outer diameter third diameter BRD3 and having third inflation pressure BRP3 that may increase by less than five percent in pressure as compared to second inflation pressure BRP2.
• Thus, according to embodiments,balloon8810 may be inflated with a plurality of selected increasing inflation volumes increasing from zero to 2.0 cubic centimeters. In some cases,balloon8810 may be inflated with a plurality of selected increasing inflation volumes that including increasing inflation volume from 0.05 cubic centimeters to 0.2 cubic centimeters by steps of additional controlled volumes in increments of between 0.005 cubic centimeters in volume and 0.05 cubic centimeters in volume (e.g., such as 0.01 cubic centimeters in volume), to form a plurality of predictably increasing outer diameters that increase to an outer diameter between 1.25 millimeters and 18 millimeters in diameter, by steps of between 0.2 millimeters and 0.4 millimeters increase in diameter. For instance,balloon8810 may be inflated by selected increasing inflation volumes to cause the outer diameter to increase to a plurality of predictably increasing outer diameters that are equally spaced increments in diameter between 0.2 millimeters and 0.4 millimeters, such as to increase outer diameter by 0.25 millimeters for each selected increasing inflation volume untilballoon8810 is inflated to an outer diameter sufficient to occlude a blood vessel. It is also considered thatballoon8810 may be inflated with an inflation pressure of between 0.5 atmospheres and six atmospheres in pressure, such as to reach a sufficient outer diameter to occlude a blood vessel. Additionally,FIGS. 66A andB show balloon8810 having third diameter BRD3 which may or may not be sufficient to occludeblood vessel990 at region ofinterest996.
• FIG. 67A shows the cannula and balloon ofFIG. 66A, with the balloon inflated to a selected fourth inflation volume.FIG. 67B is a cross-sectional view ofapparatus8800 ofFIG. 67A from perspective “A”. Here,balloon8810 is inflated to fourth inflation volume BRV4, fourth inflation pressure BRP4, fourth length BRL4, and fourth diameter BRD4. For example,FIGS. 67A andB show balloon8810 inflated to a selected increasing fourth inflation volume BRV4 to form a predictably increasing fourth outer diameter BRD4 and to have a fourth inflation pressure BRP4 that may be greater than first inflation pressure BRP1, second inflation pressure BRP2, or third inflation pressure BRP3 by less than five percent in pressure. Thus,balloon8810 may be inflated to fourth inflation volume BRV4 sufficient to cause fourth inflation pressure BRP4 to allowballoon8810 to occludeblood vessel990 at region ofinterest996, such as to occlude a flow or volume of fluid such as blood and/or treatment agent from passing throughblood vessel990past balloon8810 indirections8860. According to embodiments, fourth inflation volume BRV4 may be a total inflation volume of gas or fluid up to 2.0 cubic centimeters, such as a volume of between 0.03 cubic centimeters and 0.4 cubic centimeters (e.g., where inflation volume, such as fourth inflation volume BRV4 may be a total inflation volume of gas or fluid withinballoon8810, and does not include any gas or fluid withincannula8802, or within a lumen, a tube, an inflation lumen, a catheter, a shaft, or other structure related to inflatingballoon8810 extending withincannula8802 or withing balloon8810).
• In addition, fourth inflation pressure BRP4 may be an inflation pressure of between one atmosphere and six atmosphere in pressure, such as a pressure between three atmosphere and four atmosphere, or between four atmosphere and five atmosphere in pressure. Note, fourth inflation pressure BRP4 may be within five percent of any of inflation pressures BRP1 through BRP3, thus any of inflation pressures BRP1 through BRP3 may also be between one atmosphere and six atmosphere in pressure, or may in fact be equal to fourth inflation pressure BRP4. Further, according to embodiments, BRP3 or BRP4 may be a pressure sufficient to occlude the blood vessel without radially expanding the blood vessel appreciable, such as by expanding the blood vessel by less than five or ten percent in outer diameter.
• Also, according to embodiments,balloon8810 may include a property such that when inflated to a first inflation volume (e.g., such as third inflation volume BRV3)balloon8810 has a first inflated axial length (e.g., such as third length BRL3) and an outer diameter (e.g., such as third diameter BRD3) of the balloon exerts a first inflation pressure (e.g., such as third inflation pressure BRP3) on an inner diameter of a blood vessel (e.g., such as blood vessel990) sufficient to occlude the blood vessel at a region of interest (e.g., such as region of interest996). Moreover, when inflated to a second greater inflation volume (e.g., such as fourth inflation volume BRV4)balloon8810 has a second inflated axial length (e.g., such as fourth length BRL4) that is sufficiently greater than the first inflated axial length (e.g., such as third length BRL3) to allow the outer diameter of the balloon (e.g., fourth diameter BRD4) of the balloon to exert a second inflation pressure (e.g., such as fourth inflation pressure BRP4) on the inner diameter of the blood vessel (e.g., such as blood vessel990) that is less than appreciable, such as by being less than five percent greater than the first inflated pressure (e.g., such as third inflation pressure BRP3). Specifically, as shown inFIGS. 67A and B, whenballoon8810 is inflated to fourth inflation volume BRV4, instead of growing to fifth inflation diameter BRD5,balloon8810 is constrained by the inner diameter ofblood vessel990 and only grows to fourth diameter BRD4 (e.g., where fourth diameter BRD4 is a diameter that may be within five or 10 percent of third diameter BRD3). Hence, forballoon8810 to retain fourth inflation pressure BRP4 equal to or within five percent of third inflation pressure BRP3, instead ofballoon8810 growing in diameter to fifth diameter BRD5, the balloon grows axially in length to fourth length BRL4, which is greater than third length BRL3, and which is greater than first length BRL1 by BRLI1 plus BRLI2.
• To design a balloon that limits fourth inflation pressure BRP4 as described above consideration or selection of the following may be made: a deflated length of the balloon, a target inflated outer diameter of the balloon, the diameter and characteristics of the cannula, deflated balloon diameter, balloon wall thickness, type of inflation gas or liquid, type of balloon material, diameters of the plurality of predictably increasing radial balloon outer diameters, volumes of the plurality of selected increasing balloon inflation volumes, inner diameter of the blood vessel at the region of interest, blood or fluid flow pressure in the blood vessel proximate to the balloon, inflation pressure of the balloon during occlusion, actual outer diameter of the balloon in the blood vessel during occlusion, and other appropriate considerations such as those described herein.
• For instance, first length BRL1 may be selected between eight and 10 millimeters in length for a balloon to have a final radial outer diameter of 3.25 millimeters (e.g., such as if fourth diameter BRD4 were equal to 3.25 millimeters). Similarly, a first length BRL1 of between five and six millimeters may be selected for a balloon to have a final radial outer diameter of 4.25 millimeters (e.g., such as a fourth diameter BRD4 of 4.25 millimeters). Also, in an embodiment,balloon8810 may have a preinflated outer diameter (e.g., such as first diameter BRD1) of between one millimeter and three millimeters in diameter, and inflated outer diameter (e.g., such as fourth diameter BRD4) of between four millimeters and seven millimeters at an inflation pressure (e.g., such as fourth inflation pressure BRP4) of between three atmosphere and four atmosphere in pressure, while having an inflated axial length that increases with increasing inflation volume (e.g., such as third length BRL3 increasing to fourth length BRL4 with third inflation volume BRV3 increasing to fourth inflation volume BRV4) to allow the balloon to occlude a blood vessel (e.g., such as blood vessel990) while the balloon inflated outer diameter (e.g., such as fourth diameter BRD4) maintains an inflation pressure (e.g., such as fourth inflation pressure BRP4) of between three atmosphere and four atmosphere pressure on an inner diameter of the blood vessel (e.g., such as on an inner diameter ofblood vessel990 at region of interest996).
• Furthermore,balloon8810 may be designed to inflate by select increasing inflation volumes to a total inflation volume which is greater than, or oversized as compared to, an inner diameter of a blood vessel, such as by being greater than an inner diameter of a blood vessel by a selected diameter. Specifically, referring toFIGS. 67A and B, it is possible to inflateballoon8810 to a plurality of selected increasing inflation volumes up to third volume BRV3 and then to increase the inflation volume to fourth volume BRV4 to target fifth diameter BRD5 which is greater than the inner diameter ofblood vessel990 byoversized diameters8870 plus8872. For example,oversized diameters8870 plus8872 may add to be a diameter distance in a range of between 0.1 millimeters and one millimeter in diameter distance, such as by totaling to be 0.25 millimeters in diameter.
• Examples ofballoon8810 contemplated include a balloon having an inflated outer diameter (e.g., such as fourth diameter BRD4) of between 1.25 millimeters and 12 millimeters in diameter (e.g., such as if fourth diameter BRD4 were between four millimeters and seven millimeters in diameter), and an inflated length that increases in inflated length by a total length of up to 15 millimeters (e.g., such as by increasing by a total increased length of BRLI1 plus BRLI2). Specifically, in accordance with embodiments,balloon8810 may having an inflated length that increases in inflated length by a total length that is inversely proportional to the preinflated length of the balloon. For instance, as shown inFIGS. 64A-67B,balloon8810 may increase by a total increased length of BRLI1 plus BRLI2 of 0.5 mm for a balloon preinflated first length, BRL1 of eight mm (e.g., here, BRL4 is 8.5 mm), and increase by a total increased length of BRLI1 plus BRLI2 of 0.25 mm for a balloon preinflated first length, BRL1 of 10 mm (e.g., here, BRL4 is 10.25 mm) It is also contemplated that examples ofballoon8810 may have a wall thickness that decreases by between 10 percent and 75 percent in thickness, at an inflation pressure (e.g., such as fourth inflation pressure BRP4) of between three atmosphere and four atmosphere in pressure.
• In asecond example balloon8810 may have first diameter BRD1 of 1.3 millimeters at first inflation pressure BRP1 below one atmosphere in pressure, and fourth diameter BRD4 between four millimeters and seven millimeters at fourth inflation pressure BRP4 of between three atmosphere and four atmosphere in pressure. Specifically, in this case,balloon8810 may have an inner diameter of 0.044 inches and a wall thickness of 0.003 inches when deflated, such as when at first inflation volume BRV1.
• In another instance,balloon8810 may have first diameter BRD1 of 1.3 millimeters and be designed to expand to fifth diameter BRD5 of 14 millimeters when inflated to fourth inflation pressure BRP4 of between one and six atmosphere in pressure, withoutballoon8810 bursting or permanently deforming. In other words,balloon8810 may expand to several times its original diameter under low pressure (e.g., such as fourth inflation pressure BRP4 of less than six atmosphere in pressure) and then return to its original low profile dimension upon inflation volume release (e.g., such as by returning to first diameter BRD1 upon reducing inflation volume from fourth inflation volume BRV4 to first inflation volume BRV1). Thus,balloon8810 may return to almost its original size upon or after deflation. For example, after inflation,balloon8810 may return to an outer diameter that is within 10 percent of its preinflated diameter (e.g., such as within 10 percent of first diameter BRD1), an axial length within 10 percent of its preinflated axial length (e.g., such as within 10 percent of first length BRL1), and a wall thickness of within five percent of its preinflated wall thickness. Additionally, according to embodiments,balloon8810 may include a property such that during deflation it forms a plurality of decreasing radial outer diameters, such as by forming radial outer diameters third diameter BRD3, second diameter BRD2, and first diameter BRD1 during deflation from fourth inflation volume BRV4 back down to first inflation volume BRV1.
• Furthermore, according to embodiments,balloon8810 may be made of or include a balloon material having one or more of a block copolymer of polyether and polyester (e.g., such as a polyester sold under the trademark Hytrel® of DUPONT COMPANY), a biocompatible polymer such as a polyether block amide resin (e.g., for instance, PEBAX® of ATOCHEM CORPORATION), a styrene isoprene styrene (SIS), styrene butadiene styrene (SBS), styrene ethylene butylene styrene (SEBS), polyetherurethane, ethyl propylene, ethylene vinyl acetate (EVA), ethylene methacrylic acid, ethylene methyl acrylate, and ethylene methyl acrylate acrylic acid. It is also contemplated thatballoon8810 may include a material from a material family of one of styrenic block copolymers and polyurethanes; and/or a melt processible polymer.Balloon8810 may also include a low durometer material, such as a material to allow the walls or outer diameter ofballoon8810 to gently occlude a blood vessel during infusion of therapeutic agents such as stem cells, genes, adenovirus, progenitor cells, and other treatment agents as described herein.
• It is to be appreciated thatballoon8810 may be formed by melt extruding a material, such as balloon material described above, into a tube to form a balloon, and then bonding the balloon or tube to a cannula, such as a catheter orcannula 8802. For example, a balloon or tube as described above can be bonded by laser, heat, shrink tube, and/or adhesive bonding to a catheter or cannula. Specifically, according to embodiments, a tube or balloon may be shrink tube bonded tocannula8802 such as atproximal attachment8809 anddistal attachment8811 so that exterior surface ofballoon8810 forms symmetrical shapes with respect to an axis ofcannula8802 whenballoon8810 is inflated over a range of inflation volumes. For example, shrink tube bonding may be used tobond balloon8810 tocannula8802 so that when the balloon is inflated from first inflation volume BRV1 to fourth inflation volume BRV4,balloon8810 forms a plurality of symmetrical shapes, such asfirst shape8820,second shape8822,third shape8824, andfourth shape8826 during inflation. More particularly, such shrink tube bonding may include an even or straight perpendicular radial bond of a balloon or balloon tube to a cannula with respect to an axis of the cannula to effect a symmetrical inflation of the balloon over a range of selected inflation volumes as mentioned herein. Hence,cannula8802 may function as one or more of a guide catheter, a delivery catheter, and a guidewire catheter; whileballoon8810 may inflate to expand in size to an outer diameter in a range of between one millimeter and 15 millimeters in diameter, such as to occlude a blood vessel injuring treatment infusion to a region of interest of the blood vessel.
• According to embodiments, a balloon high compliance balloon, such asballoon8810, may be heat bonded, laser bonded, shrink tube bonded, or attached with an adhesive to a cannula, such as cannula8802 (e.g., orcannula9502 as shown inFIGS. 69A-70 and described in accompanying text, or a catheter as describe herein). Specifically, a balloon (e.g., such as any balloon, occlusion device or filter device as described herein) may be shrink tube bonded to a cannula so that the balloon exterior surface inflates to symmetrical shape with respect to an axis of the cannula. For instance, shrink tube bonding may provide and even and straight bond of a balloon tube to a cannula with respect to an axis of the cannula to effect such symmetrical inflation of the balloon over a range of inflation volumes as mentioned herein.
• Hence, a balloon may have a balloon outer diameter growth rate that changes in correlation to a percentage change in the inflation volume of gas or fluid (e.g., such as fluoroscopy contrast media) within the balloon. For instance, it is possible to design a high compliance balloon formed of a material and by a process as described herein, having a length of between two millimeters and 20 millimeters, and a double wall thickness between about 0.0003 inches and about 0.0038 inches, such that an outer diameter of the balloon can inflate from one millimeter when deflated to 18 millimeters when inflated without bursting or permanently deforming.
• Specifically, a high compliance balloon formed of PEBAX63D can be designed to have a deflated outer diameter and length to achieve a growth rate greater than about 40% while maintaining an inflation pressure that increases by less than five percent. For instance,FIG. 68 is a graph showing the relationship between the outer diameter of a balloon and the volume of inflation contrast fluid injected into the balloon. Here,FIG. 68 plots outer diameter of theballoon8881 versus volume of inflation contrast fluid injected into theballoon8882 for a 4.0 millimeter outer diameter by 10 millimeter long balloon of PEBAX63D operating at an inflation pressure below four atmospheres.
• Note that althoughFIGS. 64A-68 show and the related discussion describes inflatingballoon8810 with selected inflation volumes to occlude a blood vessel, it can be appreciated that a balloon (e.g., including balloon8810) may be designed by a process and/or of the materials described herein and may have a dimension, characteristic, deflated outer diameter, and/or deflated length, such that the outer diameter of the balloon may be inflation pressure controlled. More particularly, a balloon may be designed by a process and/or of the materials described herein to have an outer diameter that can be controlled by controlling the amount of inflation pressure of a gas (e.g., such as air, carbon dioxide, or a gas having a fluoroscopy contrast agent) or a liquid (e.g., such as water, saline solution, or a fluid having a fluoroscopy contrast agent) used to inflate the balloon. Again, such a balloon may be used as an occlusion device.
• Hence, a balloon as described herein (e.g., such as balloon8810) can be used with a cannula or catheter (e.g., such as cannula8802) that has a dimension suitable for percutaneous advancement through a blood vessel to infuse a treatment agent (e.g., such as biological agents) into a region of interest, such as arterial vessels and/or venous vessels. For example,FIG. 69A is a side perspective view of a cannula having a balloon attached to its distal end and an infusion lumen and accessory lumen running through the cannula.FIG. 69A shows apparatus9500 havingcannula9502 withproximal end9504 anddistal end9506.Cannula9502 may be a cannula or catheter as described herein such as a cannula similar tocannula710 or any of the various other guide, delivery, and/or guidewire catheters or cannulas described herein. For instance,cannula9502 may be include materials as described above forcatheter302 and/or512, such asmay one or more of a synthetic or natural latex or rubber, such as a polymer material; a polyetheramide; a plasticiser free thermoplastic elastomer; a thermoplastic blend; a block copolymer of polyether and polyester; a biocompatible polymer such as a polyether block amide resin; a polycarbonate or acrylonitrile bubadiene styrene (ABS); a biocompatible polymer such as a polyether block amide resin; a styrene isoprene styrene (SIS), a styrene butadiene styrene (SBS), a styrene ethylene butylene styrene (SEBS), a polyetherurethane, an ethyl propylene, an ethylene vinyl acetate (EVA), an ethylene methacrylic acid, an ethylene methyl acrylate, an ethylene methyl acrylate acrylic acid, a material from a material family of one of styrenic block copolymers and polyurethanes, a melt processible polymer, a low durometer material, and nylon.
• Balloon9510 is axially connected toexterior surface9508 ofcannula9502 atproximal coupling9509 anddistal coupling9511, at or adjacentdistal end9506.Balloon9510 may be a balloon, occlusion device, or filter device such asballoon2647,3147,3522,3947,2547,3047,3604,3704,3804,4004,308,2204,2250,2112,314,4520,4620,4820,8810, or other balloons or occlusion devices, as described herein. For example,balloon9510 may be a balloon including a property such that when inflated to a selected inflation volume the balloon will expand in size to an outer diameter sufficient to occlude a blood vessel as described herein. In one example,balloon9510 may be a high-compliance balloon made of a low durometer material and/or it may function similarly toballoon8810 as described herein.
• In addition,cannula9502 may haveinfusion lumen9520 extending fromproximal end9504 todistal end9506 and exiting infusion opening9522 distal toballoon9510. Furthermore,cannula9502 may also includeaccessory lumen9530 extending fromproximal end9504 todistal end9506 and exitingaccessory opening9532 distal toballoon9510.
• Thus, according to embodiments,infusion lumen9520 and/oraccessory lumen9530 may be adapted to have a guidewire, such as guidewire9533 disposed therethrough to guidecannula9502 through a blood vessel (e.g., such as blood vessel990) to a region of interest (e.g., such as region of interest996). For instance,infusion lumen9520 and/oraccessory lumen9530 may be adapted to have a guidewire disposed therethrough to guidecannula9502 to a location in a blood vessel as described herein with respect todelivery catheter310 as shown and described with respect toFIG. 3,cannula720 as shown and described with respect toFIGS. 7-19, and/or cannula9902-9904 as shown and described with respect toFIGS. 86-89. More particularly cannula9502 may have a dimension and/or profile compatible with or suitable to be received within, and/or be slidably disposed within a guide catheter (e.g., such as a guide catheter or cannula as described herein, including guide catheter302) having an outer diameter in a range of between 5 French and 9 French. It is also contemplated thatcannula9502 may have a dimension suitable for percutaneous advancement through a blood vessel such asblood vessel990.
• FIG. 69B is a cross section view offirst section9556 of apparatus9500 ofFIG. 69A from perspective “A”.FIG. 69B showscannula9502 having outer diameter COD1 less than 0.09 inches. It is also contemplated thatcannula9502 may include a shaft having an outer diameter which is less than 0.06 inches in diameter.FIG. 69B also showsaccessory lumen9530 having inner diameter ALID1 andinfusion lumen9520 having inner diameter ILID1. According to embodiments inner diameter ALID1 may be less than inner diameter ILIDI. In addition, it is contemplated thatinfusion lumen9520 may have inner diameter ILIDI greater than 0.01 inches in diameter.
• Also,accessory lumen9530 may have an inner diameter that is greater than between 0.01 inches and 0.5 inches in diameter, such as an inner diameter capable of accommodating a guidewire having a diameter of at least 0.01 inches. Furthermore,lumen9530 may be used to infuse a treatment agent to a region of interest, and/or to aspirate fluids from a region of interest (e.g., seehole988 ofFIG. 9 and accompanying text).
• It is also contemplated thataccessory lumen9530 may have a dimension suitable to allow for several usages including continuous guidewire access during an infusion process to maintain the location ofcannula9502, to monitor pressure distal toballoon9510, to allow for accessibility of other accessories to a location distal toballoon9510. For example,accessory lumen9530 may allow for accessibility of a flow and pressure wire to measure distal flow and pressure, and/or other types of sensor wires to make measurements in a location of a blood vessel distal toballoon9510. Specifically,accessory lumen9530 may have a dimension suitable to allow a device to be connected to a proximal end of the accessory lumen, such as at proximalaccess lumen port9554, or for a device to be disposed throughaccessory lumen9530 to measure one of chronic renal failure (CRF), electrocardiogram (EKG), oxygen level, pressure, flow, blood sampling, and/or temperature, such as at region ofinterest996. Moreover, it is contemplated thataccessory lumen9530 may be used to measure or to receive a device to measure various other physiological parameters, such as at region ofinterest996 distal toballoon9510.
• According toembodiments infusion lumen9520 and/oraccessory lumen9530 may each include a surrounding material, sleeve, cannula or lumen, such as by being constructed with composite tube. For example, the composite tube may include a braid or coil reinforced polyamide or polymer tube. Thus,infusion lumen9520 and/oraccessory lumen9530 may include a reinforced tube, to prevent catheter or lumen (e.g., such as lumen9502) kinking. Note, that composite accessory or infusion lumen such as described above with respect toballoon section9511,third section9558 and fourth section9559 also help maintain lumen roundness.
• Infusion lumen9520 and/oraccessory lumen9530 may be adapted to receive a guidewire and/or have a guidewire disposed therein and exiting a proximal opening at proximal end9506 (e.g., such asopening9532 and/or opening9522), so thatcannula9502 can be used in an over-the-wire fashion, and/or have the guidewire removed therefrom. It is also considered thatinfusion lumen9520 and/oraccessory lumen9530 may have a proximal opening, such asport9554 and/or9552 located proximal toballoon9510 and within 35 centimeters of the distal end ofcannula9502 such thatcannula9502 can be used in rapid exchange fashion.
• FIG. 69C is a cross sectional view ofsecond section9557 of apparatus9500 ofFIG. 69A from perspective “B”.FIG. 69C showssecond section9557 ofcannula9502 having width CW1 between 0.03 inches and 0.05 inches, such as a width of 0.04 inches.FIG. 69C also showscannula9502 having height CH1 between 0.04 inches and 0.06 inches, such as a height of 0.055 inches.
• FIG. 69D is a cross sectional view ofballoon section9511 ofFIG. 69A from perspective “C”.FIG. 69D showsballoon9510 including a property such that when inflated to inflation volume BIV1, such as a selected inflation volume, the balloon will expand in size to outer diameter BOD1 sufficient to occlude a blood vessel. For example,balloon9510 may include a property such that the balloon has inflation pressure BPI1 of less than five atmospheres in pressure at inflation volume BIV1.
• Moreover, according toembodiments balloon9510 may have a property such that when inflated to a plurality of increasing inflation volumes, the balloon forms a plurality of increasing radial outer diameters, and has an inflation pressure that increases by less than five percent in pressure over the range of the increasing inflation volumes. For example,FIG. 70 is a cross sectional view of the balloon section ofFIG. 69A from perspective “C”, with the balloon inflated to a second volume that is less than that shown inFIG. 69D.FIG. 70shows balloon section9511 afterballoon9510 inflated with inflation volume BIV2 which is less than volume BIV1 to form radial outer diameter BOD2 which is less than BOD1. Thus, although the inflation volume ofballoon9510 can be increased from inflation volume BIV2 to BIV1, the inflation pressure ofballoon9510 may increase from pressure BPI2 to pressure BPI1, where pressure BPI1 is less than 105% of BPI2 in pressure. For example,balloon9510 may be a balloon that expands in size to an outer diameter, such as diameter BOD1, in a range of between one millimeter and 15 millimeters in diameter, controlled by volume injection, such as to inject volumes BIV2 and BIV1 of a gas and/or a fluid.
• Cannula9502 may further includeballoon inflation lumen9540 extending fromproximal end9504 toballoon9510 and exiting and inflation opening (not shown) withinballoon9510.Balloon inflation lumen9540 and the inflation opening may have a diameter sufficient to inflate and deflateballoon9510 as described herein, such as by having a diameter of between 0.01 inches and 0.02 inches in diameter. Also,infusion lumen9520 may have an inner diameter that is at least 0.015 inches in diameter. In addition,balloon inflation lumen9540 may be connected to an inflation device or syringe to inflateballoon9510 as described herein.
• It is also to be appreciated thatcannula9502 may include additional cannula or lumen extending throughcannula9502, such as fromproximal end9504 todistal end9506, or otherwise as described herein. Moreover, according to embodiments, each ofinfusion lumen9520,accessory lumen9530,inflation lumen9540, and/or other lumen described herein may include or have its own sleeving, cannula, or other surrounding material or structure having a dimension to fit within the surrounding cannula in which the lumen is disposed or extending through. For example, each ofinfusion lumen9520,accessory lumen9530, andinflation lumen9540 may include an independent sleeve of material extending through cannula9502 (e.g., such as by fitting withincannula9502 and restricted to the dimension ofcannula9502 as described herein) and function as described herein with that sleeving.
• In addition, as shown inFIG. 69A,accessory lumen9530 may extend first length LL1,infusion lumen9520 may extend second length LL2 and inflation lumen may extend third length LL3 in distance beyond or out ofproximal end9504, where at least one of the first length LL1, second length LL2, and/or third length LL3 is a different distance in length than at least one of the others. Also, it is to be appreciated thataccessory lumen9530 being of a dimension suitable to infuse a first volume of treatment agent to a region of interest (e.g., such as region of interest996) and to ask for a second volume of blood and treatment agent from the region of interest. Similarlyballoon inflation lumen9540 may have a dimension suitable to inflateballoon9510 with a volume of (e.g., such as volume BIVI) a gas and/or liquid to an inflation pressure (such as inflation pressure BPI1) of less than 6 atmospheres and maintain the inflation volume and/or inflation pressure for at least 4 minutes.
• As shown inFIG.69A cannula9502 may haveluer adaptor9550 at or attached toproximal end9504. Thus,accessory lumen9530,infusion lumen9520, and/orinflation lumen9540 may extend throughluer adaptor9550 or be attached toluer adaptor9550 atproximal end9504. It is also considered thatluer adaptor9550 may include proximal end ofaccess lumen9534, proximal end ofinflation lumen9544, and/or proximal end ofinfusion lumen9524. Correspondingly, proximal end ofaccess lumen9534 may end with proximalaccess lumen port9554, proximal end ofinflation lumen9544 may end withballoon inflation port9553.Luer adaptor9550 may include a port, such as proximal access lumen,port9554 to connect to a hemastatic valve. Furthermore, proximal end ofinflation lumen9524 may end withproximal infusion port9552, such as a port having a spring loaded pressure seal. Also,balloon inflation port9553 may be a port to have an inflation device or syringe attached thereto as described herein. Some embodiments of inflation device or syringes contemplated for use with apparatus9500 are discussed herein with respect toapparatus9700 and9800 ofFIGS. 75A-81. For instance, an inflation device or syringe attached toballooninflation port9553 may include a label on its surface such as to identify a purpose and/or information related to the device or syringe.
• According to embodiments luer adaptor may have a dimension suitable to allow a first volume of treatment agent to be infused to a region of interest, to allow a second volume of blood and treatment agent to be aspirated from the region of interest (e.g., seehole988 ofFIG. 9 and accompanying text), and to allow a volume of a gas and/or fluid to inflateballoon9510 to a pressure, such as BPI1, of less than six atmospheres, and to maintain the inflation volume (e.g., such as BVI1) for at least four minutes.
• FIG. 69E is a cross sectional view ofthird section9558 ofFIG. 69A from perspective “D”.FIG. 69E showsthird section9558 ofcannula9502 having second width CW2 of between 0.035 inches and 0.055 inches, such as having a width of 0.048 inches.FIG. 69E also showscannula9502 having a second height CH2 of between 0.05 and 0.065 inches, such as a height of 0.057 inches. For instance, according to embodiments,third section9558 may be a section that extends from a proximal end ofballoon9510 to a distal end ofballoon9510, such as a balloon shaft. More particularly,third section9558 may includeballoon section9511, and may have a profile that is taller and/or wider thansecond section9557, such as a profile shown inFIG. 69E resulting fromthird section9558 includingballoon9510.
• FIG. 69F is a cross section view of fourth section9559 ofFIG. 69A from perspective “E”.FIG. 69F shows fourth section9559 having third width CW3 of between 0.03 inches and 0.045 inches, such as having a width of 0.037 inches.FIG. 69F also shows fourth section9559 having third height CH3 of between 0.05 inches and 0.065 inches such as having a height of 0.057 inches. According to embodiments,balloon inflation lumen9540 does not extend into eitherthird section9558 or fourth section9559.
• For example, the distal end ofcannula9502 may have a soft tip having a plurality of compliant tubes, lumen, sub-cannula with extended portions extending past the distal end of the cannula, where the extended portions are bound together by a compliant material wrap. Specifically, for example, as shown in fourth section9559 ofFIGS. 69A and 69F,infusion lumen9520 and/oraccessory lumen9530 may be joined to or joined by a soft tube made with a polymer material that is bondable to the infusion and/or accessory lumen tube. Moreover, the polymer may have a lower hardness Durometer than either the tube ofinfusion lumen9520 or the tube ofaccessory lumen9530. In addition, the soft section described above may be further wrapped with another soft jacket wrapping over the soft tubes to form the tip ofcannula9502. It is contemplated that all the joining and wrapping described above may be performed with laser bonding, heat melting, and/or adhesive gluing.
• Also, according to embodiments,cannula9502 may havesupport mandrel9560 disposed within the cannula and exiting or ending atproximal end9504 and extending proximal to, within the length of, or distal toballoon9510. Specifically,mandrel9560 may extend to balloon9510 such as shown byballoon section9511 and may or may not extendpast balloon9510, such as shown by third cross section958. Thus,mandrel9560 may extend throughthird section9558 to support apparatus9500 through the third section, whereexterior surface9508 and/orcannula9502 may not exist through the third section. It is also contemplated thatsupport mandrel9560 may have a partial length, such as beginning atproximal end9504 or beginning distal toproximal end9504 and extending to the midpoint betweenproximal end9504 anddistal end9506, a point alongfirst section9556, or a point alongsecond section9557. In addition, as a marker band, shrink wrap, infused material, extruded material, laser-bonded material, heat-bonded material, or other material or wrap may be used to couple, attach, or connectmandrel9560,accessory lumen9530, and/orinfusion lumen9520 withinballoon section9511. For example, as described below, a radio-opaque marker band, material infused fromthird section9558, and/or material that is included inthird section9558 may extend through a portion or all ofballoon section9511 to connecte together or be a part ofinflation lumen9540,accessory lumen9530,infusion lumen9520, and/orsupport mandrel9560.
• It is also considered that where materials described above with respect tothird section9558 extend intoballoon section9511, materials included in or used to form fourth section9559 may also exist or form components of the structure withinballoon section9511 and/orthird section9558 as described herein.
• Moreover, according to embodiments,mandrel9560 may have various cross-sectional shapes, such as a circle, oval, square, rectangle, or other polygon or curved cross-sectional shape asmandrel9560 extends throughcannula9502. For example,mandrel9560 may have outer diameter MOD1 which is constant, or which reduces with extension of the mandrel fromproximal end9504 towarddistal end9506. For example,mandrel9560 may have a constant outer diameter MOD1 of less than 0.017 inches in diameter. Alternately,mandrel9560 may have proximal outer diameter MOD1 that begins with less than 0.017 inches atproximal end9504 and steps down to a plurality of lesser outer diameters that end with a distal diameter of the MOD2 between 0.012 inches and 0.003 inches in diameter such as shown inFIG. 70.
• In addition, it is contemplated thatsupport mandrel9560 may be anchored or attached to a proximal adaptor such asluer adaptor9550,cannula9502 atproximal end9504, as well ascannula9502 within the length ofballoon9510, such as where the balloon is connected to the exterior surface of the cannula. It is also contemplated thatsupport mandrel9510 may only be attached at one or none of the locations identified above.
• Support mandrel9560 may be used to add stiffness to and/or reinforcecatheter9520, such as to prevent the catheter from kinking.Support mandrel9560 may include one or more of titanium, nickel-titanium (NiTi), stainless steel, a plastic, a polymer, a polyether block amide resin having a durometer hardness of about 50 to about 70 shore D, a polyimide, a polyethylene, and/or other suitable materials or metals, such as those having a sufficient stiffness to prevent the cannula from kinking. For example,support mandrel9560 may extend fromproximal end9504 to a location distal toproximal coupling9517 to prevent or reduce the possibility ofcannula9502 from kinking when the cannula is not supported by a guidewire, such as is a guidewire used during insertion ofcannula9502 is removed fromaccessory lumen9530 andaccessory lumen9530 is used to monitor parameters at a region of interest.
• Note that materialcoupling infusion lumen9520,accessory lumen9530,mandrel9560, and/orinflation lumen9540 inballoon section9511 may also be coupled to or may includecannula9502, such as in embodiments wherecannula9502 extends throughballoon section9511. It may be appreciated that one or more marker bands, polymer sheaths, on other materials may be mounted around all tubes, mandrel, lumens, and/or cannula running throughballoon9510, or can be mounted over single components thereof. Thus, if a marker band is mounted over a single component, a polymer sheath may be added to bundle together more than one of the components identified above, such as within the length ofballoon9510. Specifically, a polymer sheath may bundle together cannula9502,inflation lumen9540,mandrel9560, and/oraccessory lumen9530 at a point along the length of balloon9510 (e.g., such as whereballoon9510 is coupled coupled to exterior surface9508). According to an embodiment,balloon inflation lumen9540 may extend throughexterior surface9508 and toballoon9510, andmarker band9570 may be attached tocannula9502 at the location thatballoon inflation lumen9540 exits to balloon9510 at an inflation opening. Thus, placement ofmarker band9570 may assist in bonding ofballoon inflation lumen9540 tocannula9502, may create a more resilient bond, and may protect the inflation opening.
• According to embodiments, apparatus9500 may include at least one radio-opaque marker band. For example,FIGS. 69A, 69D, and70 show radio-opaque marker band9570 around the exterior ofaccessory lumen9530,infusion lumen9520, andmandrel9560 at midpoint9516 ofballoon9510. Moreover, as described above,marker band9570 may encircle a portion ofballoon section9511 that includes material infused there from or also included inthird section9558. In addition, it is to be appreciated thatmarker band9570 may be around the exterior of cannula9502 (e.g., ifcannula9502 extends through balloon section9511),accessory lumen9530, and/orinfusion lumen9520 at midpoint9516 of the balloon,proximal end9517 of the balloon and/ordistal end9518 of the balloon (e.g.,proximal end9517 anddistal end9518 may correspond to the “shoulder” where the balloon is coupled to the exterior surface of the cannula). Note that more than one marker band may be used such as at more than one of the locations identified above.
• According to embodiments, lengths, diameters, materials, and other characteristics ofcannula9502,infusion lumen9520,accessory lumen9530,inflation lumen9540,mandrel9560,balloon9510, and/or other components mentioned with respect to FIGS.69A-F and70 may be selected so that apparatus9500 may assist in or be used for treatment agent and/or cell infusion to treat acute myocardia infraction (AMI) or other forms of loss of heart function due to heart muscle damage.
• Another example of a cannula or catheter that has a dimension suitable for percutaneous advancement through a blood vessel to infuse a treatment agent (e.g., such as biological agents) into a region of interest, such as arterial vessels and/or venous vessels is a cannula having coaxial and/or co-linear lumen extending therethrough. For example,FIG. 71A is a cross-sectional view of a cannula and a balloon, where the cannula includes coaxially aligned lumens. As shown inFIG. 71A,apparatus9100 hascannula9102 having proximal end9104 anddistal end9106 andballoon9110 axially coupled to the exterior surface of the cannula at or adjacentdistal end9106, whereballoon9110 includes a property such that when inflated, the balloon may expand in size to an outer diameter sufficient to occlude a blood vessel.FIG. 71B is a cross-sectional view ofapparatus9100 ofFIG. 71A from perspective “A”.Cannula9102 includesguidewire tube9132 extending from proximal end9104 todistal end9106 and existingguidewire opening9133.Guidewire tube9132 is part of or includesguidewire lumen9130.
• Infusion tube9122 is disposed aroundguidewire tube9132 and extends from proximal end9104 todistal end9106 and existinfusion opening9123. Also shown,infusion tube9122 includes infusion lumen9120.FIGS. 71A and B also showinflation lumen9140 defined betweeninfusion tube9122 andcannula9102. According to embodiments,guidewire tube9132,infusion tube9122, andinflation lumen9140 are coaxially aligned with an axis of cannula9102 (e.g., such as shown inFIGS. 71A and B).
• It is to be appreciated thatinflation lumen9140 extends to balloon9110 and has a dimension suitable to inflateballoon9110. Similarly,infusion tube9122 has an outer diameter sufficient to infuse a treatment agent, such as treatment agents described herein, to a region of interest distal toballoon9110. Next,guidewire tube9132 has a sufficient outer diameter and be adapted to have a guidewire disposed therethrough to guidecannula9102 through a blood vessel to a region of interest, such as described herein with respect to guiding cannula or catheters (e.g., such as cannula9502) to a region of interest of a blood vessel.
• As shown inFIG. 71B,cannula9102 may have an exterior surface that forms a circular cross-section with respect to perspective “A” whereballoon9110 is axially coupled to the exterior surface ofcannula9102. Sealing on a round shaft allows for a more concentric balloon outer diameter profiles, such as elastomeric balloon inflation profiles. A concentrically inflated balloon profile puts can put an even stress or inflation pressure on the balloon wall to seal around or occlude a blood vessel more reliably and evenly. Similarly, it is contemplated thatinfusion tube9122 may be coupled or attached to the exterior surface ofguidewire tube9132 at a location or along locations distal toballoon9110, such as adjacent to or at the distal end ofcannula9102.
• FIG. 72A is a cross-sectional view of a cannula and a balloon, where the cannula includes coaxially and co-linearly aligned lumens. As shown inFIG. 72A,apparatus9200 hascannula9202 having proximal end9204 and distal end9206 and balloon9210 axially coupled to the exterior surface of the cannula at or adjacent distal end9206, where balloon9210 includes a property such that when inflated, the balloon may expand in size to an outer diameter sufficient to occlude a blood vessel.FIG. 72B is a cross-sectional view ofapparatus9200 ofFIG. 72A from perspective “B”.Cannula9202 includesguidewire tube9232 extending from proximal end9204 to distal end9206 and existingguidewire opening9233.Guidewire tube9232 is part of or includesguidewire lumen9230.
• FIGS. 72A and B also show infusion lumen9220 defined betweenguidewire tube9232 andcannula9202. According to embodiments,guidewire tube9232 and infusion lumen9220 are coaxially aligned with an axis ofcannula9202, such as shown inFIGS. 72A andB. Inflation tube9240 is shown extending from proximal end9204 to balloon9210 and is co-linearly aligned with an axis ofcannula9202. It is contemplated thatinflation tube9240 may be attached or coupled tocannula9202 such as by adhesive, heat bonding, and/or laser bonding. Thus,guidewire lumen9330,guidewire tube9332, andinflation lumen9340 may be co-linearly aligned with an axis ofcannula9302.
• It is to be appreciated thatinflation tube9240 extends to balloon9210 and has a dimension suitable to inflate balloon9210. Similarly, infusion lumen9220 has an outer diameter sufficient to infuse a treatment agent, such as treatment agents described herein, to a region of interest distal to balloon9210. Next,guidewire tube9232 has a sufficient outer diameter and be adapted to have a guidewire disposed therethrough to guidecannula9202 through a blood vessel to a region of interest, such as described herein with respect to guiding cannula or catheters to a region of interest of a blood vessel.
• It is also contemplated thatcannula9202 may have an exterior surface that forms a circular cross-section with respect to perspective “A” where balloon9210 is axially coupled to the exterior surface ofcannula9202. Similarly, it is contemplated that infusion tube9222 may be coupled or attached to the exterior surface ofguidewire tube9232 at a location or along locations distal to balloon9210, such as adjacent to or at the distal end ofcannula9202.
• FIG. 73 is a cross-sectional view of a cannula and a balloon, where the cannula has coaxially and co-linearly aligned lumens.FIG. 73shows apparatus9300 havingcannula9302.Cannula9302 includesguidewire tube9332 formingguidewire lumen9330 is coaxially aligned with infusion lumen9320.FIG. 73 also showsinflation lumen9340 formed withincannula9302, and balloon9310 axially coupled to the exterior surface ofcannula9302. Balloon9310 may be a part of or correspond to a balloon such as described above with respect toballoon9110. Similarly, infusion lumen9320,guidewire tube9332,guidewire lumen9330, and cannula9301 may have an outer diameter, dimension, or character to function similarly to their counterparts described above with respect toFIGS. 71A and B.
• Moreover, according to embodiments, none, any, or all ofguidewire tube9132,infusion tube9122,inflation lumen9140,guidewire tube9232, infusion lumen9220,inflation tube9240,guidewire tube9332, infusion lumen9320, and/orinflation lumen9340 may include or have its own sleeving, cannula, or other surrounding material or structure having a dimension to fit within the surrounding cannula in which the lumen is disposed or extending through, such as described herein with respect tolumen9520 at FIGS.69A-F.
• Additionally, because of it's structure,apparatus9100,9200, and9300 may track better in tortuous vasculature than cannula or catheters that do not have lumen coaxially and/or co-linearly located. In addition, a coaxial and/or co-linearly constructed catheters can be easier to fabricate. For instance, various processes may be used to formapparatus9100,9200, and/or9300 ofFIGS. 71A-73. For example, one or more materials may be melt-extruded to form a multi-lumen extruded cannula having a plurality of coaxially aligned tubes with respect to an axis of the cannula, where each coaxially aligned tube has an exterior surface with a circular cross-sectional shape with respect to the axis of the cannula. Then, a balloon may be axially sealed to the circular cross-sectional exterior surface of the cannula where the balloon includes a property such that when inflated, the balloon with expand in size to an outer diameter sufficient to occlude a blood vessel (e.g., such as described above with respect to balloon9110).
• A process for formingapparatus9100,9200, or9300 ofFIGS. 71A-73, as described above may also include melt-extruding at least one material to form a number of tubes where some of the tubes may be inserted into other tubes to form a multi-tube cannula having a number of coaxially aligned tubes or co-linearly aligned tubes with respect to an axis of the cannula, where each of the tubes has a circular cross-sectional shape with respect to an axis of the cannula. Then, a balloon (e.g., as described for balloon9110) may be axially sealed to the circular cross-sectional exterior surface of the cannula.
• Next, a process for formingapparatuses9100,9200, or9300 ofFIGS. 71A-73, as described above might include placing a mandrel having a crescent-shaped cross-section within an infusion tube, placing an inflation tube on a support mandrel next to the infusion tube, wrapping the infusion tube and the inflation tube in a jacket material, inserting the jacket material into a shrink tube, and heating the shrink tube sufficiently to melt a portion of the infusion tube and the inflation tube material so that those materials are redistributed to form a cannula having the infusion tube and inflation tube coaxially aligned with respect to an axis of the cannula.
• It is also considered that a process for formingapparatus9100,9200, or9300 ofFIGS. 71A-73, as described above might include placing a round support mandrel within a portion of a guidewire tube and placing the guidewire tube within an infusion tube so the guidewire tube is coaxially aligned with the infusion tube. Note that it can be appreciated the guidewire tube and infusion tube may each have a circular cross-section with respect to an axis of the infusion tube. Next, two crescent-shaped mandrel may be placed between the guidewire tube and the infusion tube at or along a location where the support mandrel is within the guidewire tube. The two crescent-shaped mandrel may be located at opposing axial locations to form a construction. The construction described above then may be inserted into a shrink tube and heated (e.g., such as by thermal heat or laser energy) sufficiently to melt the infusion tube to a portion of the guidewire tube, to form one or more tack joints where the crescent mandrels do not support the infusion tube, and thus the infusion tube bonds to the guidewire tube.
• For example,FIG. 74A is a cross-sectional view of the apparatus ofFIG. 71A from perspective “C” prior to forming tack joints between the guidwire tube and the infusion tube.FIG. 74A shows the structure ofapparatus9100 havingguidewire opening9133 withinguidewire tube9132 andinfusion tube9122 aroundinfusion opening9123 andguidewire tube9132.FIG. 74B is the structure ofFIG. 74A after forming tack joints between the guidwire tube and the infusion tube. For instance,FIG. 74B is the structure shown ofapparatus9100 aftertack joints9470 and9472 are formed such as by heat or laser energy as described above with respect to formingapparatus9100,9200, and9300 ofFIGS. 71A-73. Thus, aftertack joints9470 and9472 are formed,FIG. 74B shows infusion openings9423 formed between attached infustion tube sections9420 and9422, andguidewire tube9132. Note that the structures and processes described above with respect toFIGS. 74A and B, such as forming tack joints, may also be applied toapparatus9200 and9300 ofFIGS. 72A-73. Furthermore, the structure and processes described above with respect toFIGS. 72A-73 may also be applied toapparatus9100 ofFIGS. 71A and B.
• Some embodiments of inflation device or syringes contemplated for use with apparatus, cannula, and catheters, described herein (e.g., includingapparatus9100,9200,9300,9500 ofFIGS. 69A-74) for inflating and/or deflating balloons described herein (e.g., such asballoon8810 and9510 ofFIGS. 64A-70) may include one or more inflation syringes. For example,FIG. 75A is a cross sectional view of an apparatus to inflate a low volume balloon to occlude a blood vessel. For example,apparatus9700, as will be shown and described below inFIGS. 75A-80 may be used to inflate a balloon coupled to a distal end of a cannula having an inflation lumen extending from the balloon through a cannula and out a proximal exit in the cannula where the lumen will be coupled toapparatus9700.FIG. 75A showsapparatus9700 havinglarge volume syringe9720 andlow volume syringe9750 within an elongated hollow inner diameter of the plunger oflarge volume syringe9720.FIG. 75B is a cross-sectional view of the apparatus ofFIG. 75A from perspective “A”.
• Large volume syringe9720 is shown havingbarrel9702 which forms an elongated hollow bodyproximal end9704, anddistal end9706.Barrel9702 ofapparatus9700 is shown cut away in the travel region of theouter plunger9703.Outer plunger9703 incorporates one or more seals onpiston9707, which do not allow fluid/air flow between the outer diameter (OD) of theouter plunger9703 and the inner diameter (ID) ofbarrel9702 in the area where they form a seal. The lumen/ID of thebarrel9702 is in communication with the output extension tube9714 andpressure gage9705, such that asouter plunger9703 is translated distally, fluid may be expelled out of the extension tube9714 and the pressure applied to the fluid may be measured. The distal end of extension tube9714 is terminated in a maleLuer Lock connector9716. Thus,large volume syringe9720 has an opening in the distal end to couple to a proximal exit of a cannula, such as by coupling maleLuer Lock connector9716 to a lumen in a cannula. More particularly, embodiments ofapparatus9700 and9800 may attach todelivery catheter2620 and/orcatheter system3000, such as by coupling maleLuer Lock connector9716 to fitting2640 as shown inFIGS. 26-29 and/or fitting3040 as shown inFIG. 30.
• The position of theouter plunger9703 in thebarrel9702 may be locked into position or unlocked to move freely by actuatingouter plunger lock9708.Outer plunger lock9708 is on the proximal end of thebarrel9702 and can have many configurations. The simplest configuration is a pressure/force engagement of the proximal portion ofplunger9703 with sufficient force and material coefficient of friction to holdplunger9703 in place when thelock9708 is engaged. For example, the basic mechanism can be the similar to lock/unlock mechanisms for use on balloon inflation devices, indeflators and syringes.
• According to embodiments,outer plunger9703 is longitudinally slidable withinbarrel9702 and has a first shaft withfirst piston9707 disposed on the first shaft distal end. In accordance with embodiments,first piston9707 and the shaft have elongated hollowinner diameter9740 withinner plunger9709 longitudinally slidable within the inner diameter.Inner plunger9740 has a second shaft withsecond piston9710 disposed on the second shaft distal end. Therefore, the inner diameter and second plunger definelow volume syringe9750 having a volume relatively substantially less than a volume oflarge volume syringe9720.
• For example,low volume syringe9750 is may communicate with the draw volume of internal volume oflarge volume syringe9720 inbarrel9702 distal toplunger9707. For example,outer plunger9703 is a hollow construction in whichinner plunger9709 resides.Inner plunger9709 may containseals9710 which perform the same function for theinner plunger9709 and the ID of theouter plunger9703 asseals9707 do for theouter plunger9703 and the ID of thebarrel9702. In its most distal travel position, the distal end of theinner plunger9709 aligns with or is very close to the distal end of theouter plunger9703. If the distal position of theinner plunger9709 is too far proximal of the distal end of theouter plunger9703, then it is possible that air could get trapped in the ID of theouter plunger9703 that is distal to the distal end of theinner plunger9709. As previously explained, trapped air is not desirable and should be avoided in these applications. In one design, the ID of thebarrel9702 is designed such that it can accommodate a significant protrusion of theinner plunger9709 distal to the distal end of theouter plunger9703 and distal to theseals9710.
• Also,apparatus9700 may include one or more lock mechanisms to lock the plunger of each syringe so that a user can selects whether the plunger is free or constrained to move in response to the rotation of its threads or a lock can be used to engage the plunger surface(s) with sufficient friction to prevent accidental plunger motion (in this case the threads aren't really needed to provide the mechanical advantage to more easily produce high pressures, since the pressures are to be low), the plunger handle configuration modified to make accidental motion less likely (i.e. from a “T” shape to a more round shape). As shown inFIG. 75A,low volume syringe9750 may have its own associated translation and locking control. Specifically,large volume syringe9720 may useouter plunger lock9708 to releasablysecure plunger9703 to lockpiston9707 at various locations alongbarrel9702. Correspondingly,low volume syringe9750 may useinner plunger lock9711 to releasablysecure plunger9709 to lockpiston9710 at various locations alonginner diameter9740. Thus,inner plunger lock9711 is on the proximal end of theouter plunger9703 and allows the locking and unlocking of theinner plunger9709 position relative to theouter plunger9703.Inner plunger lock9711 may have a mechanism similar to that of theouter plunger lock9708.
• The maximum proximal travel position of the inner plunger is constrained to limit the amount of fluid that may be drawn into the ID of outer plunger9703 (or alternatively or in addition to limit the minimum protrusion of the distal end of theinner plunger9709 into the ID of barrel9702). Many mechanisms are commonly used to accomplish this, the most common utilize OD or cross-section changes of the plunger9709 (and/or the ID of the outer plunger9703) to interfere with portions of the device that it must translate through, such as thelock9711. (A similar method may be used to constrain the proximal travel of theouter plunger9703.) The limiting ofplunger9703 or9709 travel sets the fluid displacement allowed for that plunger. In a design for a compliant balloon, the displacement set forinner plunger9709 is the maximum incremental injection that can be safely injected into the catheter to incrementally inflate the balloon or less. This is an important safety feature.
• In addition, according to embodiments, the proximal end of theouter plunger9703 may contain a mechanism to allow the selection of different proximal travels ofinner plunger9709 and, thus allow a single inflation/deflation device to safely operate catheters with different inflation or deflation volumes. Alternately or in addition, the previously mentioned proximal travel limit (used to initially limit the inflation of a compliant balloon) may be removed (a distal limit may be added) and theinner plunger9709 may subsequently be used to more rapidly inflate and deflate the balloon. Alternately or in addition, the proximal end of theouter plunger9703 may contain a mechanism to control the translation of inner plunger. Such mechanisms can be incorporated as a part of thelock9711 mechanism.
• It can be appreciated that the translation control on the second plunger or other components of the device (i.e. the first plunger) may contain an indicator or marks that show the expected size of the balloon or the expected sizes of various balloon catheters and/or their expected deflation volumes. The translation control on the second plunger may contain a selection mechanism that limits the plunger translation to a safe maximum injection volume for the selected catheter.
• More particularly, according to an embodiment,large volume syringe9720 may have large drawing volume, such as between 10 cubic centimeters (cc) in volume and 30 cubic centimeters in volume; andlow volume syringe9750 may have substantially smaller drawing volume, such as between 0.2 cubic centimeters in volume and three cubic centimeters in volume to inject additional controlled volumes in increments of between 0.005 cubic centimeters in volume and 0.05 cubic centimeters in volume.
• For example, in order to allow a balloon (e.g., such as a low pressure, high compliance, and/or low tension occlusion balloon as described herein with respect toballoons4420,8810, and/or9510) to be conveniently and quickly deflated and then accurately re-inflated,apparatus9700 may includelatch mechanisms9760 and9762 to unlatchinner plunger lock9711 frominner diameter9740 so thatpiston9710 can be moved towardsproximal end9704. Thus, when unlatched,piston9710 may be moved towardsproximal end9704 ofinner diameter9740 to evacuate a selected volume of fluid from the balloon and intolow volume syringe9750. Furthermore,latch mechanisms9760 and9762 may be configured to latchinner plunge lock9711 back toinner diameter9740 so thatpiston9710 can be moved towardsdistal end9706 to return or deliver a selected volume of fluid to the balloon. More particularly, latching or re-latchinginner plunger lock9711 toinner diameter9740 may return the same volume of fluid evacuated from a balloon and intolow volume syringe9750, as described above, whenpiston9710 is moved towards the proximal end of hollowinner diameter9740 and returned to its original position.Latch mechanisms9760 and9762 will be described further below with respect toFIGS. 76-80.
• Inner plunger lock9711 may also include an adjustment mechanism to adjust the position ofpiston9710 to various locations along hollowinner diameter9740. For example,inner plunger lock9710 may include threadedcavity9770 coupled toknob9730 which is exterior to hollowinner diameter9740. Thus,bolt9772 may threadably engage threadedcavity9770 and be coupled toplunger9709 so thatknob9730 may be rotated to adjust a position ofpiston9710 to various locations alonginner diameter9740. More particularly,knob9730 may include indicia disposed about the knob to indicate a selected volume of fluid to be communicated to or from the balloon corresponding to the marked position on the knob, such thatknob9730 may be rotated to various marked positions to inflate the balloon with various selected volumes of an inflation gas or liquid. For instance,knob9730 may be rotated from a first position to a balloon volume position to deliver a selected volume of fluid to the balloon. On the other hand,knob9730 may be rotated from the balloon volume position back to the first position to evacuate the same selected volume of fluid from the balloon and intoapparatus9700.
• It can be appreciated thatpiston9710 and/or9707 may each include one or more sealing members adapted to create a fluid seal between the piston and the elongated hollow in which the piston is slidably disposed (e.g., such as by including one or more elastic O-rings).
• FIGS. 76-80show latch mechanisms9760 and9762, andknob9730 adjusted to various positions, such as positions they may be adjusted to during use of innerplunger lock mechanism9711 and/orapparatus9700. For instance,FIGS. 76-80 show what effect latching andunlatching mechanisms9760 and9762, and/orrotating knob9730 to various positions have on the position ofpiston9710.FIG. 76 shows the latch mechanisms ofFIG. 75A in an unlatched position.FIG. 76 shows latchmechanisms9760 and9762 in an unlatched position to unlatchinner plunger lock9711 from hollowinner diameter9740.Latch mechanisms9760 and9762 may include retaining structure on their proximal and distal ends so that an unlatched position, such as shown inFIG. 76 cannot be exceeded andinner plunger lock9711 cannot be separated frominner diameter9740.FIG. 76 also showsgap9780 betweeninner plunger lock9711 andinner diameter9740.Latch mechanisms9760 and9762 may be used to provide an unlatched position, such as shown inFIG. 76, so thatlow volume syringe9750 may be filled with liquid and/or bubbles my be removed therefrom.
• FIG. 77 shows the latch mechanisms ofFIG. 76 relatched.FIG. 77 showsFIG. 76 afterlatch mechanisms9760 and9762 are used to reattach or latchinner plunger lock9711 toinner diameter9740. The latch positions shown inFIGS. 76 and 77 may be used to remove bubbles or air fromlow volume syringe9750, such as by alternating between the latch positions shown inFIGS. 76 and 77 forlatch mechanisms9760 and9762 to remove bubbles or air fromlow volume syringe9750. After bubble/air removal, the latch position oflatch mechanisms9760 and9762 may be returned to the latched position as shown inFIG. 77.
• FIG. 78 showsFIG. 77 after the inflation volume adjustment knob has been rotated or turned to retain fluid.FIG. 78 showsFIG. 77 afterknob9730 has been rotated or turned, such as to draw in or retain a maximum amount of fluid withinlow volume syringe9750. As shown inFIG. 78,bolt portion9772 is in a most proximal position, as to wherebolt portion9772 is in a most distal portion inFIG. 77. The travel ofbolt portion9772 may be limited such that the maximum fluid volume that may be retained (and then expelled into the balloon) is limited to an amount that limits the maximum outer diameter to which the balloon may be inflated. Thus, a limit to the travel ofbolt portion9772 may be selected (e.g., such as as a safety feature) to prevent over-inflation/bursting of the balloon and/or over-stretching of the blood vessel to be occluded.
• FIG. 79 showsFIG. 78 after the inflation volume adjustment knob has been rotated or turned to inflate the balloon with a selected inflation volume fluid.FIG. 79 showsknob9730 turned or rotated to inflate a balloon, such as to occlude a blood vessel. Note thatFIG. 79shows bolt portion9772 between a minimum and maximum distal position along threadedcavity9770, such as whenknob9730 is being rotated to various rotational positions as indicated by markings to provide selected volumes of fluid to the balloon.
• FIG. 80 showsFIG. 79 after unlatching inner the plunger lock to deflate the balloon.FIG. 80 showsFIG. 79 after unlatchinginner plunger lock9711 frominner diameter9740. For example,latch mechanisms9760 and9762 are in an unlatched position and allow forgap9780. Thus, the configuration shown inFIG. 80 may be used after the balloon is inflated with a proper volume to occlude a blood vessel and it is desired to deflate the balloon to allow blood to perfuse back into a region of interest of the blood vessel, such as region ofinterest996 ofblood vessel990. More particularly, after a blood vessel is sufficiently occluded and treatment agent is infused through a region of interest for a sufficient period of time,inner plunger lock9711 may be unlatched frominner diameter9740 so thatplunger10 may be pulled to a distal position to deflate the occluding balloon to allow blood to reflow through the portion of the blood vessel previously occluded.
• After the position shown inFIG. 80, it is then possible to re-latchinner plunger lock9711 toinner diameter9740, such as by pushingknob9730 forward to returnapparatus9700 to the position that is shown inFIG. 79. Thus, it is possible to alternate between the positions shown inFIG. 79 andFIG. 80 in order to inflate a balloon to a sufficient volume to occlude a blood vessel is described herein, then deflate the balloon sufficiently to allow blood flow through the blood vessel, and then re-inflate the balloon to the same volume of inflation fluid that the balloon was inflated with prior to deflation.
• Thus, the apparatus and steps shown and described with respect toFIGS. 75A-80 provide a safe and predictable device and process for inflating, deflating, and re-inflating and a high compliance, low pressure, and/or low tension balloons for occlusion of a blood vessel. For instance,latch mechanisms9760 and9762 allowapparatus9700 to be used to safely more rapidly inflate and deflate a low volume balloon after an initial inflation.
• FIG. 81 shows an alternate embodiment of an apparatus to perform the functions ofFIGS. 75A-80. As shown inFIG. 81,apparatus9800 haslow pressure indeflator9882 which may be a large volume syringe having a functionality similar to that described above with respect tolarge volume syringe9720.FIG. 81 also shows controlled volume indeflator9881, which may have a functionality similar to that described above with respect tolow volume syringe9750.Indeflator9881 and9882 are coupled to three-way stop cock9883 which is in turn coupled toextension line9884 and rotatingmale luer9885. In turn,luer9885 is coupled to occlusion/infusion catheter9889. And balloon9880 is coupled tocatheter9889. Thus,apparatus9800 may provide a balloon inflation and deflation functionality similar to that described above with respect toapparatus9700. Thus, in accordance with embodiments a balloon may be inflated byapparatus9700 or9800 havinglarge volume syringe9720 orlow pressure indeflator9882 which may be a high volume, low pressure syringe for initially inflating the balloon to a controlled and/or selected low pressure initial diameter. Then, the balloon may be further inflated bylow volume syringe9750 or controlled volume indeflator9881 ofapparatus9700 or9800, which may be a low volume syringe for further inflating the balloon with controlled volume increments (e.g., such as selected low volume increments of inflation fluid) to produce controlled diameter increase(s) up the an occlusion diameter.
• It can be appreciated thatapparatus9700 or9800 may be low pressure inflation/deflation device that requires only one operator and the normal stopcock connections, and still provide the ability to effectively evacuate the air, to inflate the balloon to its nominal out diameter (OD), to subsequently control the injected inflation volumes (for a compliant balloon) and/or the subsequent withdrawn volumes (to allow subsequent rapid balloon deflations and inflations) to the desired degree of precision, to lock the injected inflation volumes (so the device may be set aside) and unlock the injected inflation volumes (so the balloon may be deflated).
• For examplelarge volume syringe9720 provides a large volume capacity to allow a vacuum/low pressure to be drawn on a device via normal Luer connected components that may leak a little air under dry/low pressure (relative to air pressure) conditions and to allow for any relatively low pressure/higher volume initial filling steps, while subsequently providing for very controlled/adjustable small volume injections and withdrawals. As such,large volume syringe9720 can be used to remove air from a catheter and balloon, and subsequently inflate the balloon with contrast to a low pressure (to its beginning/initial OD or desired OD). Then,low volume syringe9750 can be used to inflate the balloon (e.g., such as a balloon as described herein, includingballoons4420,8810, and9510) with additional controlled small volumes of contrast to be adjustably injected to bring the compliant balloon controllably up to the desired OD in steps to occlude a vessel and/or to withdraw/inject a controlled small volume of contrast to subsequently rapidly and safely deflate and re-inflate the balloon.
• Apparatus9700 or9800 may be designed to effectively remove the air in a balloon and its inflation lumen so that only a small residual volume of air remains (air which will be replaced with the inflation fluid) to allow the balloon's OD to be effectively controlled by the volume of the injected fluid. One inflation fluid used is contrast. Contrast allows the balloon and its location to be very easily imaged by conventional fluoroscopy. As the OD of a compliant balloon is stepped up or a relatively non-compliant balloon is inflated to a low pressure, contrast may be injected proximal of the balloon into the vessel (normally via the guiding catheter) to assess whether the desired occlusion has been obtained or not.
• It is also contemplated thatapparatus9700 or9800 may be designed to have a relatively large drawing volume (usually in the 10-30 cc range) compared to the volume of air leaked, to maintain a sufficiently low pressure for effective air removal. Thus, usingapparatus9700 or9800, it is possible to first inflate a compliant balloon to its nominal OD (its lowest OD) at a specified low pressure and then inject additional controlled volumes to produce the larger OD's. For instance, a balloon may be inflated with controlled volumes with increments on the order of 0.005 to 0.05 cc (or smaller) with a maximum total on the order of about 0.5 cc (or less) to control the balloon OD effectively.
• Next a process for percutaneous advancing one or more cannula or catheters through a blood vessel to treat or infuse a treatment agent (e.g., such as biological agents) into a region of interest, such as arterial vessels and/or venous vessels is described.
• For example,FIG. 82 is a flow diagram of a process for treating a region of interest of a blood vessel with one or more treatment agents and/or progenitor cells. Atblock9610, a region of interest of a blood vessel is identified. For example, a region of interest may be similar to region ofinterest996 ofblood vessel990; or may be a treatment zone of a blood vessel, a coronary vein, a coronary artery, or an infarct artery may be identified such as by releasing a marker into the blood vessel and marking ischemic signal at a location or region. Also, a region of interest includes those described above with respect to block9610 as well as a location of a blood vessel, such asblood vessel990, proximal to a treatment zone, such as a zone to be treated with a treatment agent (e.g., which may include progenitor cells).
• Moreover, if sufficient ischemic signal does not exist prior to treatment of a blood vessel, it is possible to precondition a region of interest to allow for marking as described above. For example, atblock9620 ischemic preconditioning of a region of interest can be performed, such as by occluding a region of interest (e.g., such as region ofinterest996 or a region of interest in the myocardium) for a period of time between 30 minutes and 180 minutes prior to releasing the marker fluid into the blood vessel. More particularly, a balloon or occlusion device as described herein may be inflated to block the blood vessel just above a targeted location of the vessel with respect to the direction of blood flow for a sufficient period of time to increase the ischemic signal from that location sufficiently for the marker to mark.
• At block9630 a cannula may be percutaneously advanced through a blood vessel. It is contemplated that the cannula may be a guide catheter, delivery catheter, guidewire, or other catheter or cannula as described herein (e.g., such ascannula8802 or9502). For example, the cannula may have a proximal end, a distal end, and a surface at or adjacent a distal end axially coupled to a balloon. For example, at block9638, the cannula to be advanced through a blood vessel may include a lumen adapted to have a guidewire disposed therethrough so that a distal end of a guidewire (e.g., which may or may not have an occlusion balloon or balloon that may be inflated to an outer diameter greater than the inner diameter of the blood vessel at the location, such as to fix the guidewire distal end) may be advanced percutaneously through a blood vessel to or beyond a region of interest so that the cannula may be advanced over the guidewire, such as by inserting and sliding the guidewire lumen over the guidewire to advance the distal end of the cannula through the blood vessel and to the region of interest.
• Specifically, a cannula such as8802 or9502 may be advanced through a blood vessel such as990 and may have a balloon such asballoon8810 or9510 axially coupled to the cannulous exterior surface at or adjacent the distal end of the cannula. In one example, the cannula may have an outer diameter of less than 0.09 inches and include a lumen extending from the proximal end to the distal end of the cannula, where the lumen has an inner diameter greater than 0.010 inches.
• Atblock9640 it is determined whether the tip of the cannula and/or the balloon has been advanced to the region of interest. If atblock9640 the cannula and/or balloon is not at a region of interest, the process returns to block9630 or the cannula and/or balloon may be advanced further. On the other hand, if atblock9640 the cannula and/or balloon is at a region of interest, the process continues to block9650.
• Atblock9650 the balloon is inflated to occlude the blood vessel. For example, a balloon such as a balloon described above with respect to block9630 may be inflated from a first diameter (e.g., such as first diameter BRD1 as described above) to a different second diameter (e.g., such as fourth diameter BRD4 as described above) that is at least equivalent to an inner diameter of a blood vessel to occlude the blood vessel at a region of interest (e.g., such as a region of interest as described above with respect to block9610) for a first period of time. For example the balloon may be inflated by controlling a volume of a gas and/or a fluid injected into the balloon, such as to inflate the balloon to a plurality of increasing inflation volumes to form a plurality of increasing radial outer diameters. Moreover, it is contemplated that the increasing inflation volumes may be increased to a volume corresponding to a radial outer diameter of the balloon which is greater than the radial inner diameter of the blood vessel at a region of interest.
• Furthermore, according to embodiments, as described with respect toballoon8810, the balloon may have a property such that when inflated to such a volume, the balloon has an inflation pressure that increases by less than five percent in pressure than the inflation pressure at one or more of the previous inflation volumes. For example, the balloon may be a high compliance balloon that increases in inflated axial length sufficiently to cause the balloon inflated outer diameter to maintain an inflation pressure that is within five percent of the previous pressure on the inner diameter of the blood vessel while the inflation volume is increased.
• Atblock9660 treatment agents are infused to the region of interest. For example, a treatment agent as described herein and/or a plurality of progenitor cells (e.g., such as progenitor cells suspended in a liquid) may be infused through a lumen extending from a proximal end to a distal end of the cannula and exit in outlet portal at the distal end of the cannula (e.g., such as by being infused throughlumen9520 and exitingoutlet port9522 distal to balloon8810 or9510 as described above). According to embodiments the progenitor cells may be bone marrow derived progenitor cells such as those produced by: (1) harvesting bone marrow, (2) selecting stem cells from bone marrow, and/or (3) deriving cells from bone marrow aspirates. It is also contemplated that the progenitor cells may be blood derived progenitor cells, such as those produced by: (1) collecting venous blood, (2) purifying mononuclear cells, and/or (3) ex-vivo culturing of mononuclear cells. It is to be appreciated that the region of interest being treated may be in the blood vessel of the same person from which the progenitor cells are derived (e.g., the progenitor cells may be reinfused into the infarct artery of the person from which the bone marrow or blood derived progenitor cells are taken).
• In addition, it is contemplated thatblock9660 may include infusion and a therapeutic agent having one or more of cardiomyocytes, stem cells, progenitor cell, skeletal myocytes, smooth muscle cells, and endothelial cells, and growth factors such as IGF-I, HGF, VEGF, NGF, FGF, TGF-beta, and their isoforms.
• In addition, infusing atblock9660 may include infusing treatment agent and/or progenitor cells at a low pressure and distal to the occluding balloon such that a flow of blood through the region of interest is precluded and does not wash the treatment agent away from the region of interest. For example, the occluding balloon may completely preclude blood flow through the region of interest, such as region ofinterest996. Thus, an occluding balloon or device may block off blood flow from region ofinterest996 to increase treatment agent residence time in region ofinterest996, such as a capillary bed. Without such blood flow, the treatment agent residence time in the blood vessel allows for more treatment agent (e.g., such as stem cells) to adhere to the vessel wall and eventually migrate into target muscle, such as heart muscle. Also, infusing may include infusing a volume of between one milliliter and 10 milliliters of treatment agent and/or progenitor cells, such as by infusing a volume of between three milliliters and four milliliters of a progenitor cell suspension (e.g., such as 3.3 milliliters of progenitor cell suspension).
• Atblock9670 it is determined whether the first period of time has expired. According to embodiments the first period of time may be a period of time between two minutes and five minutes, such as a period of three minutes in time. If atblock9670 the first period of time has not expired, more time is allowed to elapse, and additional treatment agent and/or progenitor cells may be infused. Also, if the first period of time has not expired, other processes or measurements may be performed, such as those described herein and/or desired during an infusion treatment. Specifically, measurement and/or procedures such as those described above with respect toaccessory lumen9530 may be performed during the first period of time.
• In accordance with embodiments, one way to balance the benefit of having a long treatment agent or progenitor cell residence time at the region of interest with the risk of inducing ischemic damage to the target muscle during occlusion of the blood vessel is to provide for blood perfusion around or through the occluding device so that blood can still pass through the region of interest in a controlled amount or during a controlled time period during treatment of the region of interest.
• For instance, If atblock9670 the first period of time has expired, the process continues to block9675. At block9675, liquid (e.g., such as blood and/or a treatment agent) is allowed to perfuse from a location in the blood vessel proximal to the balloon to the region of interest (or vice versa depending on the direction of blood flow). In other words, at block9675, a liquid, such as blood and/or treatment agent, may be allowed to perfuse between a location in the blood vessel proximal to the balloon and the region of interest, such as by allowing the liquid to flow from a location proximal to the balloon to a location distal to the balloon, or vice versa. For example, the balloon may be deflated sufficiently to allow the blood vessel (such asblood vessel990 at region of interest996) to be open to a flow of fluid, such as blood. Thus, the balloon may be deflated as described herein (e.g., such as described herein with respect toballoon8810 or9510) to allow a reflow of blood through the region of interest, such as to minimize extensive ischemia. According to embodiments, at block9675 the balloon may be configured to be and may be sufficiently deflated to be subsequently reinflated after a second period of time. Moreover, at block9675 the balloon may be deflated sufficiently to be retracted from the blood vessel, such as by being withdrawn by the cannula.
• Alternatively or in addition to allowing perfusion at block9675 by deflating the balloon, a liquid (e.g., such as blood or treatment agent) may be allowed to perfuse between a location in the blood vessel proximal to the balloon and the region of interest via a lumen extending through the cannula. For example, the cannula may include a lumen extending from a location proximal to the balloon to a location distal to the balloon and a proximal hole through the exterior surface of the cannula and to the lumen at a location proximal to the balloon as well as a hole through the exterior surface of the cannula and to the lumen at a location distal to the balloon. Thus, a lumen for perfusing liquid such as is described herein with respect toapparatus9910,9920,9930, and/or9940 may be used at block9675.
• Likewise, instead of or in addition to deflating the balloon, perfusion of a liquid (e.g., such as blood and/or treatment agent) at block9675 may including retracting or pulling back a guidewire disposed through a guidewire lumen extending past at least one hole in the exterior of the cannula and to the guidewire lumen proximal to the balloon to allow liquid to perfuse between a location in the blood vessel proximal to the balloon and to a location distal to the balloon via a guidewire lumen opening in the distal end of the cannula. Specifically, for example, the cannula may include a guidewire lumen extending from a proximal end to a distal end of the cannula and exiting in opening in the cannula distal to the balloon, so that a distal end of a guidewire disposed through the guidewire lumen can be retracted to a location proximal to at least one hole through the exterior of the cannula and to the guidewire lumen, where the at least one hole is located proximal to the balloon. Furthermore, disembodiment also allows the distal end of the guidewire to be advanced to a location distal to the at least one hole through the exterior of the cannula to prohibit or reduce liquid perfusion between a location in the blood vessel proximal to the balloon and the region of interest, such as by blocking perfusion of the liquid between the blood vessel and the lumen. Specifically, the embodiment described above may be performed by an apparatus such asapparatus9600 as described herein.
• The ability to retract the distal end of the guidewire to allow perfusion and advance the distal end of the guidewire to reduce or prohibit perfusion is important since such an embodiment may provide a simple process for performing block9675 as well as repeatingblocks9650 through9685 one or more times. As withapparatus9600, it is also worth noting that the plurality of holes through the cannula exterior described above can include various numbers and size and shape holes to allow the movement of the distal end of the guidewire to control an amount of liquid perfusion between a location of the blood vessel proximal to the balloon and the region of interest.
• Atblock9680 it is determined whether a second period of time, during which the liquid is allowed to perfuse, has expired. If atblock9680 the second period of time has not expired, further time may be allowed to elapse while the liquid is allowed to perfuse. For instance, the deflated occluding, the balloon may be further deflated, the balloon may be inflated to a diameter that does not occlude the blood vessel and/or other processes or measurements may be performed. For example, measurements and/or procedures, such as those described above with respect toaccessory lumen9530, may be performed during the second period of time. Similarly, duringblock9680, perfusion may be allowed to continue as described above with respect toapparatus9910,9920,9930,9940, and/or9600. According to embodiments the second period of time may be a period of between two minutes and five minutes in time, such as a period of three minutes in time. Moreover, it is contemplated that the second period of time may be shorter than, equal to, or greater than the first period of time.
• If atblock9680 the second period of time has expired, the process proceeds to block9685. Atblock9685 it is determined whether treatment is complete. For example, according to embodiments treatment may include repetition ofblocks9650 through9685 to infuse treatment agent and/or progenitor cells a number of times to the region of interest. Specifically, blocks9650 through9685 may be repeated2,3,4,5,6, or more times to infuse treatment agent and/or progenitor cells at the region of interest. In one case, region of interest may be occluded (e.g., such as by inflating the balloon for a first period of time) (such as for three minutes) during which treatment agent and/or progenitor cells are infused to the region of interest, then blood and/or treatment agent may be allowed to perfuse into the region of interest (e.g., such as by deflating the balloon for a second period of time) (such as for three minutes). Thus, this occlusion/treatment and perfusion may be performed a total of three repetitions to infuse a total of 10 milliliters of progenitor cell suspension via three infusions of 3.3 milliliters each.
• If atblock9685 treatment is completed the process may continue to block9690. Atblock9690 the occluding balloon may be deflated and the cannula may be retracted from the blood vessel, such as by withdrawing the deflated balloon using the cannula.
• Note that it is contemplated that the process described above with respect toFIG. 82 may be controlled manually, automatically, and/or by a machine, such as bysystem controller3080, and/or according to a treatment process for infusion of a treatment agent into an artery or vein of a patient using devices, apparatus, methods, and/or processesdescribed herein (e.g., such as according to the process described with respect toFIGS. 3, 19,54,55 and/or63).
• Now, specifically addressing three types of apparatus for allowing blood and/or treatment agent to perfuse between a location in the blood vessel proximal and distal to an occluding balloon, such as is described above with respect to block9675. First, as mentioned at block9675, the occluding balloon may be deflated sufficiently to allow the blood vessel (such asblood vessel990 at region of interest996) to be open to a flow of fluid, such as blood.
• Second or in addition to allowing perfusion at block9675 by deflating the balloon, blood and/or treatment agent may be allowed to perfuse between a location in the blood vessel proximal and distal to an occluding balloon by retracting or pulling back a guidewire disposed through a guidewire lumen extending past at least one hole in the exterior of the cannula proximal to the balloon to allow perfusion to a location distal to the balloon via a guidewire lumen opening in the distal end of the cannula.
• Thus, according to embodiments, liquid, blood, and/or treatment agent perfusion between the region of interest and a location proximal to the balloon, or from a location on one side of an occlusion device to a location on the other side of an occlusion device as described herein, may be achieved by including a liquid perfusion capability through the cannula. For example, perfusion from one side of an occluded site to the other side of an occluded site may be a constant flow, a controlled amount of flow, and/or a flow that may be adjusted to start or stop the flow or provide different flow rates as controlled by an operator. For instance,FIG. 83 is a cross-sectional view of an occlusion balloon attached to a cannula having holes through an exterior surface of the cannula proximate to the balloon, where the holes extend to a lumen in the cannula having an exit distal to the balloon. Thus, a cannula described with respect toFIG. 83 may be referred to as a blood perfusion catheter or a blood perfusion cannula.FIG. 83shows apparatus9600 that may be an apparatus similar to apparatus9500 as described herein but including proximal perfusion ofsection9667 having at least one hole through the exterior surface ofcannula9602 and toaccessory lumen9530 at a location proximal toballoon8810 to allow perfusion of a liquid between a location in a blood vessel proximal toballoon8810 and to a region of interest, such as a region of the blood vessel distal toballoon8810. Specifically,FIG. 83shows holes9661,9662,9663,9664,9665, and9666 atproximal perfusion section9667 extending throughcannula9602 and toaccessory lumen9530.
• AlthoughFIG. 83shows6 holes throughcannula9602, it is contemplated that various numbers, sizes, and shapes of holes may be used atproximal perfusion section9667. For example, between 4 and 8 holes may be used according to one embodiment. Moreover, any of the holes, a combination of any of the holes, or a combination of all of the holes may have a dimension to allow perfusion of blood and/or treatment agent between a location of the blood vessel proximal toballoon8810 andaccessory lumen9530 and/or a location of a blood vessel distal toballoon8810. For example, the holes may allow perfusion of blood at a flow rate between full flow sufficient to prevent an ischemic event in the blood vessel of a patient when all of the holes are open, and a flow of a fraction of full flow to reduce or minimize wash off or washing away of a treatment agent in an occluded area of the blood vessel. Specifically, the holes atproximal perfusion section9667 andlumen9530 may have a dimension to allow for a flow of liquid of between 10 cubic centimeters per minute and 80 cubic centimeters per minute of flow of liquid atballoon8810 at a pressure of less than 240 mmHg at perfusion section9667 (e.g., such as a high systolic blood pressure for a patient).
• FIG. 84 is a cross-sectional view ofFIG. 83 from perspective “A”.FIG. 84 shows cannula9602 havingsupport mandrel9560,infusion lumen9520,inflation lumen9540, andguidewire lumen9530. Perfusion hole9561 is shown through the exterior surface ofcannula9602 and tolumen9530.Perfusion hole9661 may represent any of the perfusion holes as described above with respect to holes atproximal perfusion section9667. Also, note that according to embodiments,lumen9530 as described with respect toFIGS. 83 and 84 may have its own sleeving, cannula, or surrounding material or composite tube such as described herein with respect tolumen9520 at FIGS.69A-F. Thus,lumen9530 is shown inFIG. 84 as being disposed within or including a tube of material surrounding that lumen (e.g., wherein that, too, may be formed such as described herein for forming a lumen or tube).
• Holes, such asholes9661 through9666, atproximal perfusion section9667 may be formed by inserting a reinforcing mandrel withinlumen9530 and drilling the holes such as by a mechanical drill using a drill bit and/or a laser drilling technology to produce the holes as described herein.
• It is also contemplated thatcannula9602 may have one or more distal holes through the exterior surface of the cannula and to lumen9530 at a location distal to balloon8810 to allow or increase perfusion of liquid between a location in the blood vessel proximal toballoon8810 and region of interest or a location in the blood vessel distal toballoon8810. More particularly, blood flowing throughlumen9530 towarddistal end9506 may exitlumen9530 through holes incannula9602 distal toballoon8810 in addition toopening9532. It is to be appreciated that distal holes through the surface ofcannula9602 distal to balloon8810 may have a number, shape, and size and/or be formed as described above with respect to holes atproximal perfusion section9667.
• According to embodiments,accessory lumen9530 may be adapted to have a guidewire disposed therethrough to guidecannula9602 to a region of interest, such as described herein with respect tolumen9530 and a guidewire disposed therethrough. Additionally,lumen9530 may be adapted and/or have a dimension such that a distal end of a guidewire disposed therethrough can be extended past to a location distal to, to a location along, or to a location proximal toproximal perfusion section9667. Additionally,lumen9530 may have an inner diameter and a guidewire disposed therein, may have an outer diameter sufficient that the guidewire or a distal end thereof occludes liquid from flowing throughlumen9530 and/or from perfusion between the holes atproximal perfusion section9667 andlumen9530. Such a relationship between the guidewire and lumen allows the guidewire to be slid past one or more of the holes towardsdistal end9506 to control or stop the perfusion of liquid from an area of a blood vessel proximal toballoon8810 and to a region of interest distal toballoon8810. For example,FIG. 85 is a cross-sectional view of the apparatus shown inFIG. 83 advanced to a region of interest of a blood vessel. Thus,FIG. 85shows apparatus9600 advanced to a region ofinterest996 ofblood vessel990, and havingballoon8810 inflated to occlude a flow of blood from flowing between a location proximal toballoon8810 to region ofinterest996.
• Thus,apparatus9600 and the process described with respect toFIG. 82 may provide several benefits. For example, it may provide adequate blood supply during self or treatment agent infusion so that a patient will not enter in ischemic condition by supplying adequate perfusion or flow of blood, such as a flow of approximately four cc/minute.
• Thus,guidewire9692 may have a dimension to be slidably adjustable to extend or retractdistal end9693 to a location past none or any of holes atproximal perfusion section9667, such as to adjust an amount of liquid to perfuse between the location in the blood vessel proximal toballoon8810 andlumen9530. Specifically,FIG. 85 showsdistal end9693 extended distal tohole9662 but proximal tohole9661. Thus,blood flow9682 may perfuse throughhole9661 intolumen9530, outdistal opening9532 and to region ofinterest996. However, liquid is occluded or prohibited or reduced from flowing through or perfusing betweenhole9662 and lumen9530 (fluid is similarly prohibited or reduced from perfusing through any of the other holes shown inproximal perfusion section9667, other thanhole9661, and lumen9530).
• It is worth noting that by varying the size and/or shape of the holes inproximal perfusion section9667, such as by increasing the radial size of the holes from mostdistal hole9661 to a hole most proximal toproximal end9504, it is possible to control the perfusion flow. Thus, larger holes towardsproximal end9504 and smaller holes towardsdistal end9506 allowdistal end9693 of the guidewire to be slid to decrease the perfusion flow from full flow to a fraction of full flow such as a fraction between 1/10 and 1/100 of full flow (e.g., a fraction that may be dictated by the size of hole9661). Note that although holes inproximal perfusion section9667 are shown oriented longitudinally with respect to an axis ofcannula9602, it is contemplated that the holes may be oriented otherwise as long as they extend with a sufficient dimension to the lumen to allow for perfusion of liquid.
• Another application for this apparatus or process is to provide intermittent blood flow between treatment agent infusions without deflating an occlusion balloon, such asballoon8810. Thus, instead of deflating the balloon to allow blood perfusion or flow, the guidewire may be retracted past the holes atproximal perfusion section9667 to allow for adequate blood perfusion or flow.
• Moreover, since the apparatus and process allows for various amounts of liquid to perfuse, retraction and/or advancement ofdistal end9693 can be adjusted in response to the status of or measurements taken with respect to a patient. For example, if a patient is in severe chest pain and/or needs additional blood and/or treatment agent flow into an occluded area of a blood vessel,guidewire9692 can be retracted sufficiently or pastproximal perfusion section9667 to allow for a maximum blood flow, such as 40 cubic centimeters/minute. On the other hand, if the patient is only in slight discomfort, and does not require greater blood flow, a lower flow rate may be used by locatingdistal end9693 to a midpoint or distal to a midpoint along proximal perfusion section9667 (e.g., minimizing flow by placingdistal end9693 at such a location reduces treatment agent or cell wash off from a region of interest or treatment zone). Another application of the apparatus or process may be to continuously provide a perfusion flow rate that is a small fraction of the full flow rate during treatment agent or cell infusion for a prolonged occlusion. The low perfusion flow rate will have less impact on washing the treatment agent or cells away from the region of interest while providing some supply of blood to the region of interest or occluded region to allow for a longer infusion or treatment period.
• Third, or in addition to allowing perfusion at block9675 by deflating the balloon and/or via a perfusion lumen, blood and/or treatment agent may be allowed to perfuse between a location in the blood vessel proximal and distal to an occluding balloon via a separate perfusion lumen extending through the cannula the balloon is attached to and exiting a hole distal to the balloon and a hole proximal to the balloon.
• For example, according to embodiments, a blood perfusion cannula may be used, such as a version ofcannula9502 and/or a similar or modified process to that described with respect toFIG. 82. For example,FIG. 86 is a cross-sectional view of a cannula having a balloon attached to its distal end and a bypass lumen extending from a hole distal to the balloon to a hole proximal to the balloon.FIG. 86shows apparatus9910 having cannula9902 (e.g., such as a version ofcannula9502 described with respect to FIGS.69A-F, and 70) withproximal end9504 anddistal end9506, andballoon8810 axially coupled to the exterior of cannula9902 (e.g., such as byballoon8810 being axially coupled similarly to as described above for FIGS.69A-F, and70 with respect to attachment ofballoon9510 to cannula9502).FIG. 86 also showsguidewire lumen9530 extending through cannula9902 (e.g., such as bylumen9530 extending similarly to as described herein for FIGS.69A-F, and70 with respect toguidewire lumen9530 extending through cannula9502). Next,FIG. 86 showsinfusion lumen9920 extending fromproximal end9504 to a location proximal to balloon8810 (e.g., such as bylumen9920 being a lumen and extending such as is described herein with respect tolumen9520 extending throughcannula9502 for FIGS.69A-F, and 70).
• Notably,FIG. 86shows bypass lumen9550 extending fromproximal hole9952 proximal to balloon8810 todistal hole9954 distal toballoon8810.Proximal hole9952,lumen9950, anddistal hole9954 may have a dimension suitable to allow for perfusion of liquid between a location in a blood vessel proximal toballoon8810 and a location in the blood vessel distal toballoon8810, such as a region of interest as described herein. For example,proximal hole9952 anddistal hole9954 may be a hole such as is described herein with respect tohole9661. Thus,proximal hole9952 anddistal hole9954 may be oriented longitudinally with respect to an axis ofcannula9902. Also,lumen9550,proximal hole9952, anddistal hole9954 may have a dimension, such as a selected radius, or selected radii to control or adjust an amount of liquid to perfuse between a location distal toballoon8810 and proximal toballoon8810 such as to control an amount of blood and/or treatment agent perfusing between the locations to prevent an ischemic event in the blood vessel of a patient.
• For instance,apparatus9910 may be helpful to deliver a treatment agent such as a treatment agent described herein, including a drug, a peptide, growth factors, and other therapeutic agents (that may or may not be mixed with blood) to be delivered locally. For example, VEGF-1, an angiogenic growth factor, may be administered throughinfusion lumen9920 to deliver treatment agent to a blood vessel location to mix well with blood proximal toballoon8810, and then to flow mixed with the blood throughbypass lumen9950 at a controlled flow rate and to a region of a blood vessel distal toballoon8810 to assist in more efficient absorption of the treatment agent by local tissues proximal toballoon8810.
• In another embodiment,FIG. 87 shows the apparatus ofFIG. 86 where the infusion lumen extends to a location distal toballoon8810. Specifically,FIG. 87shows apparatus9920 having infusion lumen9921 extending fromproximal end9504 ofcannula9903 to an infusion exit through the exterior surface of the cannula at a location distal to balloon8810 to deliver treatment agent to a blood vessel location distal toballoon8810.
• Thus,apparatus9920 may be useful to deliver treatment agent such as genes, viral vectors, stem cells, and other therapeutic agents that require longer dwelling time at an infusion site to enhance delivery period. For example, to deliver autologous bone marrow mononuclear cells,apparatus9920 may be used so that those treatment agents dwell in a blood vessel distal to balloon8810 while that location of the blood vessel receives some blood flow as controlled bylumen9950,proximal hole9952, anddistal hole9954.
• Next,FIG. 88 is a cross-sectional view of a cannula having a balloon attached to its distal end, and infusion lumen to provide treatment agent to a location distal to the balloon, and a bypass lumen to allow for perfusion of liquid from the location distal to the balloon to the location proximal to the balloon.FIG. 88shows apparatus9930 having cannula9904 (e.g., such as a cannula described herein with respect tocannula9502 for FIGS.69A-F, and 70).Cannula9904 includesguidewire lumen9530,infusion lumen9920 and infusion lumen9921.Cannula9904 also includesbypass lumen9950,proximal hole9952 anddistal hole9954 to perfuse blood from a proximal location to a distal location of a blood vessel occluded byballoon8810.
• Thus,apparatus9930 may be useful for a combination of therapies with multiple treatment or therapeutic agents. For example, in order to infuse a transfection agent before delivery liposome encapsulated therapeutic DNA, the transfection agent may be infused throughproximal infusion lumen9920 to allow for sufficient mixing and distribution of the agent with blood, and then liposomes may be infused through distal infusion lumen9921 to treat a region of a blood vessel proximal toballoon8810 with transfection agents for a sufficient period of time, and a region of the blood vessel distal tolumen8810 with liposomes for a sufficient period of time. It is to be appreciated that a pressure sensing port may be added tocannula9902,9903, or9904 to monitor or control the re-perfusion rate via the cannula.
• FIG. 89 is a cross-sectional view of a cannula having two balloons attached to its distal end, and infusion lumen exiting the cannula between the balloons, and a bypass lumen to allow perfusion between a location proximal to both balloons and a location distal to both balloons.FIG. 89shows apparatus9940 havingcannula9905 withproximal end9504 anddistal end9506,proximal balloon9910, anddistal balloon9915 occluding region ofinterest9996 from a location ofblood vessel990 proximal toproximal balloon9910 and a location ofblood vessel990 distal todistal balloon9915. For example,proximal balloon9910 anddistal balloon9915 may be a balloon such as described herein with respect toballoon8810 to have a property such that when insulated to a selected inflation volume the balloons expand to an outer diameter sufficient to occludeblood vessel990 to occlude region ofinterest9996. Region ofinterest9996 may be a region of interest as described herein with respect to region ofinterest996.
• FIG. 89 also shows infusion lumen9921 andadditional lumen9981 extending fromproximal end9504 of cannula to exists through the exterior surface ofcannula9905 at locations betweenproximal balloon9910 anddistal balloon9915. Infusion lumen9921 may be an infusion lumen such as described with respect toinfusion lumen9920 or9921 ofFIGS. 86 and 87.Additional lumen9981 may be a lumen similar to infusion lumen9921 and/or may be a lumen to provide pressure sensing at region ofinterest9996, such as is described herein. Note that region ofinterest9996 may be described an inter-balloon occlusion infusion space.
• Thus,apparatus9940 creates an inter-balloon occlusion-infusion space to provide a more specific local delivery of treatment agent because treatment agents infused to region ofinterest9996 are confined betweenproximal balloon9910 and9915 and will not be washed away by blood circulation.
• In addition,FIG. 89shows bypass lumen9960 extending fromproximal hole9952 todistal hole9954.Bypass lumen9960 may function similarly to bypasslumen9950 as described above with respect toFIG. 86. For example,bypass lumen9960,proximal hole9952, anddistal hole9954 may allow for perfusion of blood and/or treatment agent from a location proximal toballoon9910 andballoon9915 to a location distal toballoon9910 andballoon9915.
• Specifically,apparatus9940 allows perfusion of blood from one side of the balloons to the other side of the balloons at all times while treatment agent may be administered to region ofinterest9996, such as to allow uninterrupted cardiac circulation throughblood vessel990. Moreover,apparatus9940 may create a static environment betweenproximal balloon9910 anddistal balloon9915 sufficient to reduce shear stress caused by circulation and to assist treatment agent attachment to the wall ofblood vessel990. Likewise, the wall tension to the walls ofblood vessel990, such as at region ofinterest9996 created by both balloons may cause the wall to be more permeable to therapeutic agents.
• It is also contemplated thatcannula9905 may include infusion lumen and/or pressure sensing lumen extending fromproximal end9504 ofcannula9905 to exit openings through the outer surface ofcannula9905 at locations proximal and/or distal toproximal balloon9910 anddistal balloon9915. Note that in such a case, the wall tension created by both of the balloons may also make the wall of blood vessel9900 proximal and distal to the balloons more permeable to therapeutic agents infused distal and proximal to the balloons.
• Thus, it is considered thatballoon8810, other occlusion balloons described herein, other occlusion devices described herein, cannula and/or catheters described herein may be used to occlude a location or infuse treatment agent to a region of interest or a location of a blood vessel, such as an artery or a vein of a human being, such as those in the human heart.
• Note that all embodiments of devices, catheter, balloon, cannula, lumen, filter devices, perfusion devices, apparatus, methods, and/or processes described herein are contemplated to include treatment of one or more human or animal blood vessels (e.g., including veins and/or arteries), intra-coronary veins, and intra-coronary arteries, such as by infusion of a therapeutic treatment agent including by retrograde infusion, intra-venous retrograde infusion, multiple catheter infusion, infusion involving multiple occlusion devices, multiple treatment agent infusion, and any combinations thereof.
• Hence, such treatment may be used to treat or repair ischemic and recently infarcted (dead) tissue, such as that resulting from acute myocardial infarction (AMI) and/or heart disease. For example such treatment may provide intracoronary infusion of progenitor cells into an infarct artery within days after AMI to allow the treatment agent to access capillaries and transmigrate into adjacent infarct artery tissues.
• It is also contemplated that both, intra-coronary veins and arteries could be treated or involved in treating a region of interest or treatment zone. In one case, intra-coronary veins and arteries are treated by retrograde insertion of a first catheter to perform multiple occlusion of intra-coronary veins to occlude around a region of interest, percutaneous insertion of a second catheter to perform occlusion of one or more coronary arteries occlude around the region of interest, and infusion of a treatment agent from the second catheter to treat the region of interest as described herein with respect to a multi-occlusion device or embodiment. It can be appreciated that this process may allow the treatment agent to access capillaries between the occlusions of the coronary veins and the coronary arteries.
• In the preceding detailed description, reference to specific embodiments were described. It will, however, be evident that various modifications and changes may be made thereto without departing from the broader spirit and scope of the appended claims. The specification and drawings are, accordingly, to be regarded in an illustrative rather than a restrictive sense.

Claims (78)

1. A system comprising at least one of the following:

a guide catheter comprising an occlusion device;

a delivery catheter comprising at least one occlusion device having a property to occlude a blood vessel without radially expanding the blood vessel, wherein the delivery catheter is received within the guide catheter; and

a guidewire comprising an occlusion device, wherein the guidewire is received within the guide catheter and/or the delivery catheter.

2. A kit comprising:

a delivery catheter comprising:

a shaft comprising a proximal end and a distal end and defining a delivery lumen through a portion thereof, the delivery lumen comprising a proximal end and a distal end;

a monitoring cannula defining a lumen therethrough, comprising a proximal end and a distal end, a portion of the monitoring cannula disposed within the shaft;

a port coupled to the distal end of the monitoring cannula;

a balloon inflation cannula defining a lumen therethrough, comprising a proximal end and a distal end, a portion of the balloon inflation cannula within the shaft;

a balloon adjacent to the distal end of the flexible shaft, the balloon comprising at least one material selected from the group consisting of polyether block amide resins, blends of polyether block amide resins, polyetheramides, a composite including an elastomeric material and EPTFE, a styrene-isoprene-styrene tri-Block co-polymer, and blends and mixtures thereof;

wherein the balloon is adapted to inflate to at least one of a predetermined volume sufficient to occlude a blood vessel without radially expanding the blood vessel and to a pre-determined pressure of about 0.5 to about 5.0 atmospheres.

3. The kit ofclaim 2, further comprising:

a guide catheter having a length and a lumen adapted to access a blood vessel, and having a diameter sufficient to receive a portion of the delivery catheter;

a pressure increasing device adapted to connect to the proximal end of the delivery lumen;

a sensing device adapted to connect to the proximal end of the monitoring cannula to sense one of pressure and fluid flow;

an inflation device adapted to connect to the proximal end of the balloon inflation cannula; and

a guidewire comprising an occlusion device, wherein the guide catheter has a diameter sufficient to receive a portion of the guidewire.

4. The kit ofclaim 2, further comprising a pressure relief valve coupled to the proximal end of the balloon inflation lumen, and a pressure transferring device comprising a proximal end and a distal end, wherein the distal end is adapted to connect to the proximal end of the delivery lumen.

5. The kit ofclaim 2, wherein at least one of the delivery lumen and the monitoring cannula is adapted to have a guide wire disposed therethrough to guide the guide catheter through the blood vessel to a region of interest, and wherein the delivery lumen is distal to the monitoring cannula defining at least one of a tapered and a staggered tip.

6. The kit ofclaim 2, wherein the guide catheter comprises a first convex curved portion; a concave curved portion distal to the first convex curved portion; and a second convex curved portion distal to the concave curved portion.

7. The kit ofclaim 2, wherein the guide catheter comprises a first guide catheter portion having a first diameter, and a second guide catheter portion having a second diameter, and the first guide catheter portion and the second guide catheter portion are coaxially and slidingly engaged.

8. The kit ofclaim 2, wherein the balloon is adapted to inflate to a diameter range of about 2 mm to about 20 mm, wherein the shaft comprises one of a polyether block amide resin having a durometer hardness of about 50 to about 70 shore D, a polyimide, and a polyethylene.

9. The kit ofclaim 2, further comprising a treatment agent to infuse into the delivery lument, wherein the treatment agent comprises at least one material selected from the group consisting of cells, stem cells, progenitor cells, bone marrow derived progenitor cells, antibodies against CD18, CD11/18, P-selectin, L-selectin, ICAM, VCAM, and TNF, estrogen and estrogen receptor agonists, growth factors, and their isoforms and downstream signaling mediators, heat shock proteins and their downstream signaling mediators, GIK, adenosine and adenosine receptor agonists, NO donors, Na/H exchange inhibitors, Na/K channel openers and their downstream signaling mediators, Ca channel inhibitors, beta-adrenergic receptor inhibitors, alpha-adrenergic receptor inhibitors, free radical scavengers, anti-oxidants, platelet inhibitors, complement system inhibitors, anti-apoptotic drugs, genes that encode the peptides listed above or their ligands, or bio-engineered cells or materials that express the peptides or glycoproteins listed above or their ligands, and mixtures thereof.

10. The kit ofclaim 3, wherein the pressure increasing device is disposable and is selected from the group consisting of a syringe, a syringe pump, a reciprocating pump, a gear pump, and a centrifugal pump having a removable and disposable rotor and pump housing; and wherein the pressure-sensing device comprises a disposable piezo-electric pressure sensor.

11. The kit ofclaim 3, wherein the inflation device comprises:

a large volume syringe comprising an elongated hollow body having a proximal end, a distal end, an opening in the distal end to couple to the proximal exit of the cannula, and a first plunger longitudinally slidable within the body and having a first shaft with a first piston disposed on the first shaft distal end, the piston and shaft having an elongated hollow inner diameter;

a second plunger longitudinally slidable within the inner diameter and having a second shaft with a second piston disposed on the second shaft distal end;

wherein the inner diameter and second plunger define a low volume syringe having a volume relatively substantially less than a volume of the large volume syringe.

12. The catheter kit ofclaim 3, wherein the pressure-sensing device further comprises a pressure measurement outlet, and the pressure increasing device further comprises a pressure measurement inlet, and the catheter kit further comprises a connection between the pressure measurement outlet of the pressure-sensing device and the pressure measurement inlet of the pressure increasing device.

13. The catheter kit ofclaim 2, wherein the balloon comprises at least two materials selected from the group consisting of a polyether block amide resins, polyetheramides, and mixtures thereof; wherein at least two materials have a Shore D Hardness less than about 70D; and wherein the balloon, upon inflation, has at least one of a conical and a tapered shape.

14. A method comprising:

accessing a vessel selected from the group consisting of external femoral, interior femoral, carotid, jugular, brachial, subclavian, and cephalic with a guide catheter;

accessing a coronary sinus with the guide catheter;

feeding a guidewire with an occlusion device and a retroinfusion balloon catheter to the coronary sinus, great cardiac vein, posterior vein of left ventricle, middle cardiac vein, small cardiac vein, or anterior cardiac vein of right ventricle through the guide catheter;

performing a venogram;

deploying the guidewire and the balloon catheter to one or more targeted vessels;

measuring a baseline parameter in the vein adjacent to a distal end of the balloon catheter;

inflating a balloon at the distal end of the balloon catheter and engaging the occlusion device at a distal end of the guidewire, sufficient to make a pressure waveform in the vein become ventricularized;

after inflating the balloon and after engaging the occlusion device, delivering a liquid comprising at least one of a drug and a treatment agent through the balloon catheter to an outlet port on the balloon catheter distal to the balloon and proximal to the occlusion device.

15. The method ofclaim 14, further comprising:

stopping the delivering of the liquid;

deflating the balloon and disengaging the occlusion device;

removing the catheter from the vessel; and

performing an infusate-uptake-enhancing procedure selected from the group consisting of electroporation, ultrasonic excitation, and photodynamic therapy.

16. An apparatus comprising:

a cannula having a dimension suitable for percutaneous advancement through a blood vessel, the cannula comprising a proximal end and a distal end;

a balloon axially coupled to an exterior surface of the cannula at or adjacent the distal end of the cannula, the balloon comprising a property such that when inflated the balloon will expand in size to an outer diameter sufficient for occlusion of a blood vessel at an inflation pressure less than sufficient to cause an axial force on an inner diameter of the blood vessel and sufficient to cause a radial expansion of the blood vessel.

17. The apparatus ofclaim 16 wherein the balloon comprises a property such that during inflation and deflation of the balloon, the balloon forms a plurality of radial outer diameters; has a property to cause a post inflation deflated outer diameter of the balloon to retract to within 20 percent of a pre inflated outer diameter of the balloon; and includes a balloon material having one of a modulus of less than 1.5 Mpa, an elongation of at least 500% at breaking, a tension set of less than 30%, and a tension strength of at least 200 MPa.

18. The apparatus ofclaim 16, wherein the balloon comprises one of a first wall thickness at a first axial distance from the distal end of the cannula and a different second wall thickness at a different second axial distance from the distal end of the cannula, and a first pre inflated outer diameter at a first axial distance from the distal end of the cannula and a second pre inflated outer diameter at a second axial distance from the distal end of the cannula such that when inflated the balloon will expand in size to a first outer diameter at a first axial distance from the distal end of the cannula and will expand in size to a different second outer diameter at a different second axial distance from the distal end of the cannula.

19. The apparatus ofclaim 16, wherein the balloon includes a material comprissing one of polyurethane, and a silicone rubber, a styrene-isoprene-styrene tri-block co-polymer with between 50 percent and 100 percent isoprene and between zero percent and 50 percent styrene, a silicone polyether urethane, and an aliphatic polymethane with polydimethyl siloxane backbone; wherein the silicone rubber is vulcanized with amino-mercaptobenzothrazole; and wherein the a styrene-isoprene-styrene tri-block co-polymer includes an additives comprising one of:

thiuram disulfide derivatives (R′R″N—(C=5)-S—S—(C=5)-NR′R″),

mercaptobenzothiazoles,

amino-mercaptobenzothrazole,

sulfides, and

azides.

20. A method comprising:

winding a plurality of layers of ePTFE onto a large mandrel;

bonding a seam between two of a plurality of second ePTFE windings;

fusing together the layers of ePTFE;

heating the layers of ePTFE at a temperature of approximately 380

degrees celsius for a duration of between 20 minutes and 30 minutes;

stretching the fused layers of ePTFE onto a small mandrel, wherein stretching comprises:

putting the small mandrel within an inner diameter of fused ePTFE layers;

stretching apart a distal end and a proximate end of the ePTFE sufficiently to stretch the inner diameter of fused ePTFE layers onto an outer diameter of the small mandrel;

compacting the stretched fused layers of ePTFE axially;

one of wrapping an outer diameter of the stretched fused layers of ePTFE with a polytetrafluoroethylene, and constraining the outer diameter of the stretched fused layers of ePTFE within a steel tube prior to compacting, and then sufficiently compacting axially inwards a distal end and a proximate end of the stretched fused layers of ePTFE, such that during inflation of the lined ePTFE balloon, the compacted stretched fused layers of ePTFE may not expand axially

bonding a balloon liner to the compacted stretched fused layers of ePTFE to form a lined ePTFE balloon.

21. An apparatus comprising:

a cannula having a dimension suitable for percutaneous advancement through a blood vessel, the cannula comprising a proximal end and a distal end; and

a filter device having a proximal portion axially coupled to an exterior surface of the cannula at or adjacent the distal end of the cannula, and a distal portion having a first diameter under a first set of conditions and a different second diameter that under a second set of conditions is at least equivalent to an inner diameter of a blood vessel at a region of interest.

22. The apparatus ofclaim 21, wherein the filter device comprises a property such that under the second condition, the filter device will restrain from flowing through the filter device a plurality of particles having a particle size greater than an average particle size of blood cells and contained in a fluid flowing through the filter device, and will allow aspiration of the plurality of particles from being restrained.

23. The apparatus ofclaim 21, wherein the filter device comprises a frame portion defined by the proximal portion and the distal portion, and a material stretched on the frame portion to form, under the second condition, a generally conical shaped inner surface, wherein the material has a plurality of openings, each of the plurality of openings having a dimension suitable to allow a fluid to pass therethrough, wherein the frame portion comprises a plurality of longitudinally disposed elements circumferentially spaced and defining a conical shape extending from the proximal portion to the distal portion, and wherein the frame portion comprises a plurality of anchors proximate to the distal portion, each of the plurality of anchors comprising a protruding barb capable of engaging tissue of a blood vessel.

24. The apparatus ofclaim 21, wherein the filter device has a property such that the first diameter can be transformed to become the second diameter in response to one of at least one tendon coupled to the distal portion of the filter device and the cannula such that actuation of the tendon transforms the distal portion of the filter device from the first diameter to the second diameter, an expansion pressure of between approximately 0.5 atmospheres in pressure and six atmospheres in pressure applied to the generally conical shaped inner surface, a self-expanding frame portion to provide the second set of conditions, at least one balloon coupled to the filter device and the cannula such that inflation of the balloon transforms the distal portion of the filter device from the first diameter to the second diameter.

25. The apparatus ofclaim 21, wherein the filter device has a property such that the second diameter can be transformed to become the first diameter in response to one of at least one balloon coupled to the filter device and the cannula such that deflation of the balloon transforms the distal portion of the filter device from the second diameter to approximately the first diameter, and at least one tendon coupled at the distal portion of the filter device and the cannula such that manipulation of the tendon transforms the distal portion of the filter device from the second diameter to approximately the first diameter.

26. An apparatus comprising:

a cannula having a dimension suitable for percutaneous advancement through a blood vessel, the cannula comprising a proximal end and a distal end;

a balloon axially coupled to an exterior surface of the cannula at or adjacent the distal end of the cannula, the balloon comprising a polymer moiety represented by the formula:

wherein PA represents a polyamide moiety, and PEth represents a polyether moiety, and n represents an integer of at least one.

27. The apparatus ofclaim 26, wherein the balloon comprises a thermoplastic blend copolymer material having one of a polyether block amide resin moiety and a polyetheramide moiety; comprises a property such that the balloon will inflate to an inflated outer diameter that will occlude a blood vessel and deflate to a post-inflated deflated diameter that will allow the balloon to be withdrawn from the blood vessel; and comprises a property such that the balloon has a pre-inflated volume and a post-inflated deflated volume approximately equal to the pre-inflated volume.

28. The apparatus ofclaim 26, wherein the balloon comprises a property such that the balloon will have at least 3 wings prior to being inflated and after being deflated,

wherein each wing has a wing length defined by the length of a line extending within the wing along a medial axis of a cross-section of the wing,

wherein a pre-inflated wing length for each wing is approximately equal to a post-inflated deflated wing length of each wing;

wherein each wing has an outer diameter point defined by a point of the wing radially farthest away from an axis of the cannula, and a wing diameter defined by a length of a straight line extending from the axis of the cannula, radially out to the outer diameter point,

wherein a pre-inflated wing diameter for each wing is approximately 30 percent less than a post-inflated deflated wing diameter.

29. The apparatus ofclaim 26, wherein the balloon comprises a property such that the balloon can achieve a volumetric expansion of greater than about 40% during inflation and can expanded to an inflated outer diameter between 1.5 mm and 18 mm in diameter, will have a double wall thickness between 0.0003 and 0.0038 inches in thickness and a minimum hoop strength of at least about 23,000 psi strength; and will have a durometer hardness of between 50 Shore D and 70 Shore D.

30. An apparatus comprising:

a cannula having a dimension suitable for percutaneous advancement through a blood vessel, the cannula comprising a proximal end and a distal end;

a balloon axially coupled to an exterior surface of the cannula at or adjacent the distal end of the cannula, the balloon comprising a property such that the balloon will inflate to an inflated outer diameter that will occlude a blood vessel and at a predetermined pressure of between 0.5 atmospheres and 5.0 atmospheres of pressure.

31. The apparatus ofclaim 30, wherein the balloon comprises a property such that the balloon will inflate to one of a predetermined volume and a predetermined inflated outer diameter.

32. The apparatus ofclaim 30, wherein the balloon comprises a property such that the balloon will inflate to an inflated outer diameter in a range of between 1.25 mm and 18 mm in diameter, and:

at an inflation pressure of 1 atmosphere the balloon will inflate to an inflated outer diameter of approximately 10% of a pre-inflated outer diameter;

at an inflation pressure of 2 atmospheres the balloon will inflate to an inflated outer diameter of at least 20% of the pre-inflated outer diameter;

at an inflation pressure of 3 atmospheres the balloon will inflate to an inflated outer diameter of at least 30% of the pre-inflated outer diameter;

at an inflation pressure of 4 atmospheres the balloon will inflate to an inflated outer diameter of at least 40% of the pre-inflated outer diameter;

at an inflation pressure of 5 atmospheres the balloon will inflate to an inflated outer diameter of at least 50% of the pre-inflated outer; and

at an inflation pressure of 6 atmospheres the balloon will inflate to an inflated outer diameter of least 60% of the pre-inflated outer diameter.

33. An apparatus comprising:

a cannula having a dimension suitable for percutaneous advancement through a blood vessel, the cannula comprising a proximal end and a distal end;

a balloon axially coupled to an exterior surface of the cannula at or adjacent the distal end of the cannula, the balloon comprising a property such that when inflated to a plurality of selected increasing inflation volumes the balloon forms a plurality of predictably increasing radial outer diameters and has an inflation pressure that increases by less than five percent in pressure.

34. The apparatus ofclaim 33, wherein the plurality of selected increasing inflation volumes increase from 0.05 cubic centimeters to 0.2 cubic centimeters by steps of between 0.005 cubic centimeters and 0.05 cubic centimeters in volume, the inflation pressure of the balloon is between 0.5 atmospheres and 5 atmospheres in pressure, the plurality of predictably increasing outer diameters increase from 2.5 millimeters and 8 millimeters in diameter by steps of 0.25 millimeters in diameter, includes a length of the balloon between 5 millimeters and 10 millimeters in length, and wherein the plurality of predictably increasing outer diameters are equally spaced increments in diameter of between 0.2 millimeter and 0.4 millimeter increase in diameter.

35. The apparatus ofclaim 33, wherein the balloon material is at least one of a styrene isoprene styrene (SIS), styrene butadiene styrene (SBS), styrene ethylene butylene styrene (SEBS), polyetherurethane, ethyl propylene, ethylene vinyl acetate (EVA), ethylene methacrylic acid, ethylene methyl acrylate, and ethylene methyl acrylate acrylic acid.

36. An apparatus comprising:

a cannula having a dimension suitable for percutaneous advancement through a blood vessel, the cannula comprising a proximal end and a distal end;

a balloon axially coupled to an exterior surface of the cannula at or adjacent the distal end of the cannula, the balloon comprises a property such that when inflated to a first inflation volume, the balloon has a first inflated axial length and an outer diameter of the balloon exerts a first inflation pressure on an inner diameter of a blood vessel sufficient to occlude the blood vessel at a region of interest, and when inflated to a second greater inflation volume, the balloon has a second inflated axial length that is sufficiently greater than the first inflated axial length to allow the outer diameter of the balloon to exert a second inflation pressure that is less than five percent greater than the first inflated pressure on the inner diameter.

37. The apparatus ofclaim 36, wherein the balloon has a pre-inflated outer diameter of between 1 millimeter and 3 millimeters in diameter, an inflated outer diameter between 2 millimeters and 20 millimeters at an inflation pressure of between 0.5 atmosphere and 4 atmospheres in pressure, and an inflated axial length that increases with increasing inflation volume to allow the balloon to occlude the blood vessel while the balloon inflated outer diameter maintains an inflation pressure of between 3 atmosphere and 4 atmospheres pressure on an inner diameter of the blood vessel; and wherein the balloon material is at least one of a styrene isoprene styrene (SIS), styrene butadiene styrene (SBS), styrene ethylene butylene styrene (SEBS), polyetherurethane, ethyl propylene, ethylene vinyl acetate (EVA), ethylene methacrylic acid, ethylene methyl acrylate, and ethylene methyl acrylate acrylic acid.

38. The apparatus ofclaim 36, wherein the balloon has a pre-inflated outer diameter of between 0.025 inches and 0.065 inches in diameter, a pre-inflated length of between 2 millimeters and 30 millimeters in length, and a pre-inflated wall thickness of between 0.002 inches and 0.02 inches in thickness, has an inflated outer diameter of between 1.25 millimeters and 12 millimeters in diameter, and a wall thickness that decreases by between ten percent and 75 percent in thickness at an inflation pressure of between 3 atmosphere and 4 atmospheres in pressure.

39. The apparatus ofclaim 36, wherein the cannula functions as one or more of a guide catheter, a delivery catheter, and a guidewire catheter; and wherein the axial coupling of the balloon to the cannula includes shrink tube bonding the balloon to a cannula such that an exterior surface of the balloon forms a symmetrical shape with respect to an axis of the cannula when the balloon is inflated over a range of inflation volumes.

40. An apparatus comprising:

a cannula having an outer diameter less than 0.090 inches, a proximal end, and a distal end;

a balloon axially coupled to an exterior surface of the cannula at or adjacent the distal end of the cannula, the balloon comprising a property such that when inflated to a selected inflation volume the balloon will expand in size to an outer diameter sufficient to occlude the blood vessel; and

an infusion lumen having an inner diameter greater than 0.010 inches extending from the proximal end to the distal end of the cannula and exiting an infusion opening distal to the balloon;

an accessory lumen extending from the proximal end to the distal end of the cannula and exiting an accessory opening distal to the balloon;

wherein at least one of the infusion lumen and the accessory lumen is adapted to have a guide wire disposed therethrough to guide the cannula through the blood vessel to a region of interest.

41. The apparatus ofclaim 40, wherein the cannula has a dimension suitable to be received within a guide catheter having an outer diameter in a range between 5 French and 9 French the accessory lumen has an inner diameter that is less than the inner diameter of the infusion lumen, and the cannula has a shaft having an outer diameter less than 0.060 inches.

42. The apparatus ofclaim 40, wherein the balloon comprises a property such that the balloon has an inflation pressure of less than five atmospheres of pressure at the selected inflation volume, the balloon comprises a property such that when inflated to a plurality of increasing inflation volumes the balloon forms a plurality of increasing radial outer diameters and has an inflation pressure that increases by less than five percent in pressure, and the balloon will expand in size to an outer diameter in a range of between 1 millimeter and 15 millimeters in diameter controlled by volume injection of one of a gas and a fluid.

43. The apparatus ofclaim 40, wherein the cannula further includes a balloon inflation lumen extending from the proximal end of the cannula to the balloon; wherein the accessory lumen extends a first length, the infusion lumen extends a second length, and the inflation lumen extends a third length in distance beyond the proximal end of the cannula, and at least one of the first, second and third length is a different distance in length; and wherein the accessory lumen has a dimension suitable to infuse a first volume of treatment agent to the region of interest; and the balloon inflation lumen has a dimension suitable to inflate the balloon with a volume of one of a gas and a liquid to an inflation pressure of less than six atmospheres.

44. The apparatus ofclaim 40, wherein at least one of the accessory lumen, the infusion lumen, and the inflation lumen are attached to a luer adapter at the proximal end of the cannula, and the luer adapter includes:

an infusion port having a spring-loaded pressure seal; and

a balloon inflation port having a syringe.

45. The apparatus ofclaim 40, wherein the accessory lumen has a dimension suitable to allow on of a device to be coupled to a proximal end of the accessory lumen and a device to be disposed through the accessory lumen to measure of one of CRF, EKG,02 level, pressure, flow, blood sampling, and temperature at the region of interest; wherein the infusion lumen and the accessory lumen each include one of a reinforcing mandrel disposed within the cannula and extending from the proximal end of the cannula to the balloon, a braid reinforced polymer tube, and a coil reinforced polymer tube; and, wherein at least one of the infusion lumen and the accessory lumen is adapted to receive the guide wire, have the guide wire disposed therein and exiting a proximal opening at the proximal end of the cannula such that the cannula can be used in an over-the-wire fashion, and have the guide wire removed therefrom.

46. The apparatus ofclaim 40, wherein the cannula further comprises a support mandrel disposed within the cannula and extending from the proximal end of the cannula to the balloon, and the support mandrel has one of a constant outer diameter of less than 0.017 inches in diameter, and a proximal outer diameter of less than 0.017 inches in diameter and steps down to a plurality of lesser outer diameters to a distal diameter of between 0.012 inches and 0.003 inches in diameter.

47. The apparatus ofclaim 46, wherein the support mandrel is anchored to at least one of a proximal adapter at the proximal end of the cannula and the cannula where the balloon is coupled to the exterior surface of the cannula.

48. An apparatus comprising:

a cannula having a proximal end, and a distal end;

a balloon axially coupled to an exterior surface of the cannula at or adjacent the distal end of the cannula, the balloon comprising a property such that when inflated the balloon will expand in size to an outer diameter sufficient to occlude the blood vessel at a region of interest;

a guidewire tube extending from the proximal end to the distal end of the cannula and exiting a guidewire opening in the distal end of the cannula;

an infusion tube around the guidewire tube extending from the proximal end to the distal end of the cannula and exiting an infusion opening in the distal end of the cannula;

an inflation lumen defined between the infusion tube and the cannula;

wherein the guidewire tube, infusion tube, and inflation lumen are co-axially aligned with an axis of the cannula.

49. The apparatus ofclaim 48, wherein the inflation lumen extends from the proximal end of the cannula to the balloon and has a dimension suitable to inflate the balloon, the infusion tube has an outer diameter sufficient to infuse a treatment agent to the region of interest distal to the balloon, and the guidewire tube has a sufficient outer diameter and is adapted to have a guide wire disposed therethrough to guide the cannula through the blood vessel to a region of interest.

50. The apparatus ofclaim 48, wherein the guidewire tube, the infusion tube, and the inflation lumen have a circular cross sectional shape with respect to an axis of the cannula; wherein the cannula exterior surface has a circular cross sectional shape with respect to an axis of the cannula where the balloon is axially coupled to the exterior surface of the cannula; and wherein the infusion tube is coupled to the exterior surface of the guidewire tube at a location distal to the balloon.

51. An apparatus comprising:

a cannula having a proximal end, and a distal end;

a balloon axially coupled to an exterior surface of the cannula at or adjacent the distal end of the cannula, the balloon comprising a property such that when inflated the balloon will expand in size to an outer diameter sufficient to occlude the blood vessel at a region of interest;

a guidewire tube extending from the proximal end to the distal end of the cannula and exiting a guidewire opening in the distal end of the cannula, the guidewire tube co-linearly or co-axially aligned with an axis of the cannula;

an infusion lumen defined between the guidewire tube and the cannula;

an inflation tube extending from the proximal end of the cannula to the balloon, the inflation tube co-linearly aligned with an axis of the cannula.

52. The apparatus ofclaim 59, wherein the infusion lumen is co-linearly or co-axially aligned with the cannula; and wherein the inflation tube extends from the proximal end of the cannula to the balloon and has a dimension suitable to inflate the balloon, the infusion lumen has a dimension sufficient to infuse a treatment agent to the region of interest distal to the balloon, and the guidewire tube has a sufficient outer diameter and is adapted to have a guide wire disposed therethrough to guide the cannula through the blood vessel to a region of interest.

53. The apparatus ofclaim 59, wherein the guidewire tube and the infusion lumen have a circular cross sectional shape with respect to an axis of the cannula; wherein the cannula exterior surface has a circular cross sectional shape with respect to an axis of the cannula where the balloon is axially coupled to the exterior surface of the cannula; and wherein the infusion tube is attached to the exterior surface of the guidewire tube at a location distal to the balloon.

54. An apparatus to inflate a low volume balloon to occlude a blood vessel, the balloon coupled to a distal end of a cannula having an inflation lumen extending from the balloon to a proximal end of the cannula and through a proximal exit in the cannula, the apparatus comprising:

a large volume syringe comprising an elongated hollow body having a proximal end, a distal end, an opening in the distal end to couple to the proximal exit of the cannula, and a first plunger longitudinally slidable within the body and having a first shaft with a first piston disposed on the first shaft distal end, the piston and shaft having an elongated hollow inner diameter;

a second plunger longitudinally slidable within the inner diameter and having a second shaft with a second piston disposed on the second shaft distal end;

wherein the inner diameter and second plunger define a low volume syringe having a volume relatively substantially less than a volume of the large volume syringe.

55. The apparatus ofclaim 54, further comprising a first lock mechanism to releasably secure the first plunger to lock the first piston at at least one location along the hollow body, a second lock mechanism to releasably secure the second plunger to lock the second piston at at least one location along the hollow inner diameter, and at least one latch mechanism to unlatch the second lock mechanism from the hollow inner diameter to move the second piston towards the proximal end of the hollow body to evacuate a selected volume of fluid from the balloon into the low volume syringe.

56. The apparatus ofclaim 55, wherein the second lock mechanism includes an adjustment mechanism to adjust the position of the second piston to at at least one location along the hollow inner diameter; and wherein the adjustment mechanism includes a threaded cavity coupled to a knob exterior to the large volume syringe and a bolt portion threadably engaging the cavity and coupled to the second plunger such that the second piston may be adjusted to at at least one location along the hollow inner diameter by rotating the knob.

57. The apparatus ofclaim 56, wherein rotation of the knob from a first position to a balloon volume position delivers a selected volume of fluid to the balloon, and rotation of the knob from the balloon volume position back to the first position evacuates a selected volume fluid from the balloon into the low volume syringe.

58. An apparatus comprising:

a cannula having a proximal end, and a distal end;

a balloon axially coupled to an exterior surface of the cannula at or adjacent the distal end of the cannula, the balloon comprising a property such that when inflated to a selected inflation volume the balloon will expand in size to an outer diameter sufficient to occlude the blood vessel at a region of interest;

a lumen extending from the proximal end to the distal end of the cannula and exiting an opening in the cannula distal to the balloon;

at least one hole through the exterior surface of the cannula and to the lumen at a location proximal to the balloon to allow perfusion of a blood and/or a treatment agent between a location in the blood vessel proximal to the balloon and the region of interest.

59. The apparatus ofclaim 58, further including a guidewire disposed through lumen and slidably adjustable such that a distal end of the guidewire can be extended past the at least one hole; wherein guidewire lumen has an inner diameter and the guidewire has an outer diameter sufficient in diameter to occlude the guidewire lumen; and wherein the at least one hole includes between four and eight holes and the guidewire has a dimension to be slidably adjustable to extend or retract a distal end of the guidewire to a location past none or any of the holes.

60. The apparatus ofclaim 58, wherein the at least one hole includes a plurality of holes having different sizes to perfuse blood at a flow rate of between a full flow and a plurality of fractions of the full flow, the different sizes increase in size from a most distal hole to a most proximate hole, and the holes are oriented longitudinally with respect to an axis of the cannula.

61. A method comprising:

advancing a cannula percutaneously through a blood vessel to a region of interest, the cannula having a proximal end, a distal end, and an exterior surface at or adjacent the distal end of the cannula axially coupled to a balloon,

inflating the balloon from a first diameter to a different second diameter that is at least equivalent to an inner diameter of a blood vessel to occlude the blood vessel at the region of interest;

infusing a treatment agent to the region of interest distal to the balloon;

perfusing a blood and/or a treatment agent flow between a location in the blood vessel proximal to the balloon and the region of interest.

62. The method ofclaim 61, wherein perfusing includes:

perfusing blood and/or treatment agent via a lumen extending through the cannula from a location proximal to the balloon to a location distal to the balloon, via a proximal hole through the exterior surface of the cannula and to the lumen at a location proximal to the balloon, and a distal hole through the exterior surface of the cannula and to the lumen at a location distal to the balloon.

63. The method ofclaim 61, wherein inflating includes inflating the balloon for a first period of time and perfusing includes deflating the balloon for a second period of time; and at least one more repetition of inflating, infusing, and deflating.

64. The method ofclaim 61, wherein perfusing includes:

retracting back a guidewire disposed through a guidewire lumen extending from the proximal end to the distal end of the cannula and exiting an opening in the cannula distal to a balloon, for a first period of time;

wherein retracting includes retracting a distal end of the guidewire from a location distal to at least one hole from the guidewire lumen through the exterior surface of the cannula and proximal to the balloon to a location proximal to the at least one hole.

65. The method ofclaim 64, further comprising advancing the guidewire to a location distal to the at least one hole to prohibit a blood and/or a treatment agent perfusion between a location in the blood vessel proximal to the balloon and the region of interest, for a second period of time, and repeating infusing, retracting and advancing at least once more.

66. The method ofclaim 64, wherein retracting includes retracting a distal end of the guidewire to control an amount of a blood and/or a treatment agent perfusion between a location in the blood vessel proximal to the balloon and the region of interest by adjusting the guidewire to extend or retract a distal end of the guidewire to a location amongst a plurality of the at least one hole to allow a blood and/or a treatment agent to perfuse between the holes and the lumen at a selected perfusion rate.

67. The method ofclaim 61, wherein infusing includes infusing a volume of a progenitor cell suspension including bone marrow-derived progenitor cells.

68. The method ofclaim 61, wherein inflating includes:

increasing an axial length of the balloon;

maintaining the inflation pressure on the inner diameter of the blood vessel.

69. An apparatus comprising:

a cannula having a proximal end, and a distal end;

a balloon axially coupled to an exterior surface of the cannula at or adjacent the distal end of the cannula, the balloon comprising a property such that when inflated to a selected inflation volume the balloon will expand in size to an outer diameter sufficient to occlude the blood vessel at a region of interest;

the cannula having a lumen having a proximal end at a location proximal to the balloon and extending to a distal end at a location distal to the balloon, a proximal hole through the exterior surface of the cannula and to the lumen at a location proximal to the balloon, and a distal hole through the exterior surface of the cannula and to the lumen at a location distal to the balloon.

70. The apparatus ofclaim 69, wherein the lumen, the proximal hole and the distal hole have a dimension suitable to allow perfusion of a blood and/or a treatment agent between a location in the blood vessel proximal to the balloon and the region of interest, and the proximal hole has a selected diameter and the distal hole has a selected diameter to control an amount of a blood and/or a treatment agent to perfuse between the selected holes and the lumen.

71. The apparatus ofclaim 69, wherein the cannula further comprises one of an infusion lumen extending from the proximal end of the cannula to a infusion exit through the exterior surface of the cannula at a location proximal to the balloon to deliver treatment agent to the blood vessel proximal to the balloon, and an infusion lumen extending from the proximal end of the cannula to a infusion exit through the exterior surface of the cannula at a location distal to the balloon to deliver treatment agent to the blood vessel distal to the balloon.

72. The apparatus ofclaim 69, wherein the cannula further comprises a first infusion lumen extending from the proximal end of the cannula to a infusion exit through the exterior surface of the cannula at a location proximal to the balloon to deliver treatment agent to the blood vessel proximal to the balloon, and a second infusion lumen extending from the proximal end of the cannula to a infusion exit through the exterior surface of the cannula at a location distal to the balloon to deliver treatment agent to the blood vessel distal to the balloon.

73. The apparatus ofclaim 69, further comprising:

a proximal balloon axially coupled to an exterior surface of the cannula proximal to the balloon, the proximal balloon comprising a property such that when inflated to a selected inflation volume the balloon will expand in size to an outer diameter sufficient to occlude the blood vessel proximal to the a region of interest;

wherein the cannula further comprises a first infusion lumen extending from the proximal end of the cannula to a first exit through the exterior surface of the cannula at a location between the balloon and the proximal balloon to deliver treatment agent to the region of interest, and a second infusion or pressure sensing lumen extending from the proximal end of the cannula to a second exit through the exterior surface of the cannula at a location between the balloon and the proximal balloon to deliver treatment agent to or sense pressure at the region of interest.

74. A catheter comprising:

a shaft comprising a proximal end and a distal end, and defining a delivery lumen through a portion thereof, the delivery lumen comprising a proximal end and a distal end;

a delivery port coupled to the distal end of the delivery lumen;

a pressure monitoring lumen, a portion of the pressure monitoring lumen disposed within the shaft, comprising a proximal end and a distal end;

a pressure port coupled to the distal end of the pressure monitoring lumen;

a balloon inflation lumen, a portion of the balloon inflation lumen disposed within the shaft, comprising a proximal end and a distal end;

a balloon adjacent to the distal end of the flexible shaft, the balloon comprising at least one material selected from the group consisting of polyether block amide resins, blends of polyether block amide resins, a composite including an elastomeric material and EPTFE, a styrene-isoprene-styrene tri-Block co-polymer, and blends and mixtures thereof;

wherein the balloon is adapted to inflate to at least an elasticity of about 40% at a pre-determined gauge pressure of about 0.5 to about 6.0 atmospheres;

a balloon inflation port within the balloon and coupled to the distal end of the balloon inflation lumen;

wherein at least one of the delivery lumen and pressure monitoring lumen are adapted to receive a guidewire.

75. The catheter ofclaim 74, wherein the delivery lumen is distal to the pressure monitoring lumen defining at least one of a tapered and a staggered tip, and the delivery lumen is adapted to receive the guidewire; or wherein the pressure monitoring lumen is distal to the delivery lumen defining at least one of a tapered and a staggered tip, and the pressure monitoring lumen is adapted to receive the guidewire.

76. A catheter comprising:

a shaft comprising a proximal end and a distal end and defining a delivery lumen through a portion thereof, the delivery lumen comprising a proximal end and a distal end;

a delivery port coupled to the distal end of the delivery lumen;

a pressure monitoring lumen comprising a proximal end and a distal end, a portion of the pressure monitoring lumen disposed within the flexible shaft;

a pressure port coupled to the distal end of the pressure monitoring lumen;

a balloon inflation lumen comprising a proximal end and a distal end, a portion of the balloon inflation lumen within the flexible shaft;

a balloon adjacent to the distal end of the flexible shaft, the balloon comprising at least one material selected from the group consisting of polyether block amide resins, blends of polyether block amide resins, a composite including an elastomeric material and EPTFE, a styrene-isoprene-styrene tri-Block co-polymer, and blends and mixtures thereof;

a balloon inflation port coupled to the distal end of the balloon inflation lumen and the balloon inflation port within the balloon;

wherein a first wall thickness of the balloon adjacent a proximal end of the balloon is smaller than a second wall thickness of the balloon adjacent a distal end of the balloon; and

wherein upon inflation, a first diameter of the balloon adjacent to a proximal end of the balloon is larger than a second diameter adjacent a distal end of the balloon.

77. The catheter ofclaim 76, wherein the balloon, upon inflation, has one of a tapered balloon shape, and a conical balloon shape.

78. A catheter comprising:

a shaft comprising a proximal end and a distal end, and defining a delivery lumen through a portion thereof, the delivery lumen comprising a proximal end and a distal end;

a delivery port coupled to the distal end of the delivery lumen;

a pressure monitoring lumen, a portion of the pressure monitoring lumen disposed within the shaft, comprising a proximal end and a distal end;

a pressure port coupled to the distal end of the pressure monitoring lumen;

a balloon inflation lumen, a portion of the balloon inflation lumen disposed within the shaft, comprising a proximal end and a distal end;

a balloon adjacent to the distal end of the flexible shaft, the balloon comprising at least one material selected from the group consisting of polyether block amide resins, blends of polyether block amide resins, a composite including an elastomeric material and EPTFE, a styrene-isoprene-styrene tri-Block co-polymer, and blends and mixtures thereof;

a balloon inflation port within the balloon and coupled to the distal end of the balloon inflation lumen;

wherein the delivery lumen is distal to the pressure monitoring lumen defining at least one of a tapered and a staggered tip, and the delivery lumen is adapted to receive the guidewire.

Images