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IL46174A - Cardiopulmonary bypass system - Google Patents

Cardiopulmonary bypass system

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Publication number
IL46174A
IL46174AIL46174AIL4617474AIL46174AIL 46174 AIL46174 AIL 46174AIL 46174 AIL46174 AIL 46174AIL 4617474 AIL4617474 AIL 4617474AIL 46174 AIL46174 AIL 46174A
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IL
Israel
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blood
bag
rate
pump
volume
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IL46174A
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IL46174A0 (en
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Baxter Travenol Lab
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Publication date
Application filed by Baxter Travenol LabfiledCriticalBaxter Travenol Lab
Publication of IL46174A0publicationCriticalpatent/IL46174A0/en
Publication of IL46174ApublicationCriticalpatent/IL46174A/en

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Abstract

An emergency alertable gravity feed cardiopulmonary bypass system is disclosed in which a blood volume responsive transducer is utilized in returning oxygenated blood to a human circulatory system at a pumping rate corresponding to venous drainage or selected norms. The transducer is coupled to a standpipe and is responsive to a confined gas volume therein related to the blood volume in a first air evacuable, gravity fed, collapsible bag and is coupled to a rate setting control. Blood flow from the first bag is directed by a control responsive oxygenation pump through a membrane oxygenator and heat exchanger and air evacuable collapsible bag and a main pump before return to the patient. The oxygenation pump rate slaved to the main pump is greater than the gravity feed rate, and a pressure relieving conduit recirculates excess blood flow from the second bag to the first bag. Supervisory control of the flow rate of the main pump may be exercised by manual adjustment of the flow rate.[US3890969A]

Description

n pam a n nay napiy naiye Cardiopulmonary bypass system BAXTER TRAVEJJGL LABORATORIES, INC.
C:- 44170 Background of the Invention 1. Field of the Invention This invention pertains to blood flow rate controllers for pump oxygenation systems and, more particularly, to venous blood feed responsive, oxygenation systems for use in cardiovascular surgery and for cardiopulmonary partial support. 2. Description of the Prior Art Generally, a cardiopulmonary bypass system is a medical system used in cardiovascular surgery, intensive care and surgical recovery that is coupled to a human body to revitalize and pump blood, thereby performing certain functions of the heart and lungs and often partially or fully bypassing a portion of the circulatory system. The cardiopulmonary bypass system receives a venous blood feed (oxygen deficient blood) from the human cir-culatory system, oxygenates and warms the blood and returns the blood to the circulatory system at a flow rate corresponding to the venous drainage, thus reducing the load on the lungs and heart.
A cardiopulmonary bypass system in a partial support capacity is used, for example, during cardiac intensive care of patients who have suffered a cardiac infarction where a portion of the heart muscle has died from an insufficient blood supply. The dead muscle is soft and difficult to suture since it will tear easily. The muscle may heal if the patient is kept quiet and heart chambers are subject to a minimum amount of pressure. Failing such care, an aneurysm may result in which the softened muscle swells up and stagnates pools of blood which tend to clot. The tendency toward development of an aneurysm is minimized by reducing the pumping load on the heart with the partial support system. Typically the infarcted tissue scars over and thereby regains its tensile integrity in several weeks during which time the cardiopulmonary bypass system must operate continuously. Recent developments in pump oxygenation equipment, such as membrane oxygenators having limited long term blood degradation effects, have made possible long term partial support of this duration. In the past, technicians have monitored the flow of blood in pump oxygenation systems for a relatively short period of time, such as less than four hours, during heart surgery. However, the costs and availability of technicians generally preclude their usage on a long term basis, and * even where they are used human error can be a significant problem.
Conflicts between safety, costs and flexibility must be reduced to provide a satisfactory cardiopulmonary bypass system. Such desirable features include responsive-ness to a gravity feed rate, minimal blood degradation and long term reliability. In addition, the exposure of the blood to air should be minimized, while the buildup of excess gases should be avoided or at least indicated.
Many specific requirements must be met in a practical partial support system. For example, the cardiopulmonary bypass system experiences a load as the blood is returned to the human body. The load is variable and the flow impedance seen by the cardiopulmonary bypass system may increase if for example the arteries are constricting or decrease when hemorrhaging is occurring. Yet the cardiopulmonary bypass system should generally maintain a constant flow rate to the human body, equal to the venous drainage. In the past, the return flow rate has been controlled in response to central venous pressure or return flow pressure. See, for example, Turina, et al., "An Automatic Cardiopulmonary Bypass Unit for Use In Infants", The Journal of Thoracic and Cardio-vascular Surgery 63 (February 1972), p. 263, 264. However, venous pressure is an inaccurate measure of blood flow and may vary considerably for a constant blood flow depending on the physical state of the patient.
Blood removal from the human circulatory system by a cardiopulmonary bypass system should not cause an excessive vacuum or suction so as to collapse the veins, yet provide a substantial and generally uniform blood flow to effectively unload the patient's cardiopulmonary system. A system utilizing a negative pressure in a caval cannula is described in an article by Turina et al., "Servo-controlled Perfusion Unit With Membrane Oxygenator for Extended Cardiopulmonary Bypass", Biomedical Engineering (March 1963) pp. 102-107. The Turina system however, is rather sophisticated and complex in utilizing sensors and servos for a number of controls, and thus is both unduly costly and subject to greater tendency to failure.
The rate and changes in rate of blood flow indicate the physical state of the patient, and thus it would be desirable to monitor the blood flow rate. The physician may find it necessary to increase or decrease the return flow rate of the blood. Increasing the blood flow rate in excess of the drainage rate often requires the addition of blood to the system. It would be advantageous to have a cardiopulmonary bypass system which could introduce quantities of blood to the blood flow in addition to the blood supplied by the patient's circulatory system.
The quantity of blood flowing in the circulatory system of a neonate or young infant is extremely critical. For example, hyaline membrane disease attacks the alveolar sacks of infants. When this occurs, the lining of the lungs is impervious to oxygen and CC^* Since the infant having this disease receives insufficient oxygen, the treatment in the past has been to increase, in concentration and pressure, the oxygen provided to the infant. Although the disease is often cured by this technique, other serious conditions may set in which are caused by the toxic effects of oxygen such as retrolental fibroplasia, in which the retina is destroyed. By using a cardiopulmonary bypass system, the lungs are allowed to heal. The control of blood volume is extremely important since the hyaline disease typically occurs with underweight infants, typically less than 2500 grams and having a total blood volume of only 150-300 cc.
Thus it would be desirable to have a cardiopulmonary bypass system that is safe, reliable, gravity feed responsive, and volume alterable.
Summary of the Invention In broad terms, a cardiopulmonary bypass system for use with a human circulatory system in accordance with this invention comprises variable volume, air-free means for collecting a gravity feed blood flow from a patient and transducer means coupled to the collector means for providing a blood volume responsive signal related to the feed rate of the blood. After oxygenating and warming the blood from the collector means, pump means coupled to the collector means returns the blood to the patient at a flow rate controlled by the signal from the transducer means such that the blood flow returning to the patient is substantially the same as the drainage rate from the patient.
In a preferred embodiment of the invention, a first collapsible bag is coupled to receive a gravity fed flow of blood. The bag is collapsible and air evacuable so that any blood-gas interface may be substantially eliminated. The bag is also flexible so as to inhibit air suction when empty and thereby prevent an air embolism to the circulatory system.
A standpipe extending from the bag is coupled to a gas pressure responsive transducer. The standpipe provides a confined gas volume, the pressure within which acts on the transducer.
Blood flow rate changes into the bag manifested by blood volume changes of the bag result in fractional changes in the confined gas volume and subsequent pressure changes that are much amplified with respect to the fractional blood volume changes of the bag. A second collapsible bag is provided that functions generally in a buffer capacity and supplies revitalized blood to the patient. Revitalization means generally comprising a pump, a membrane oxygenator and a heat exchanger is coupled between the first and second bags. A recirculation path communicating between the second bag and the first bag provides a positive recirculation of a part of the blood flow, relieving excess pressure in the second bag and insuring equilibrium in the flow rates. A main variable speed pump coupled to the second bag delivers a controlled blood flow from the second bag to a human circulatory system. To regulate pump speed, a rate setting contro responsive to the transducer signal drives the main pump at a rate which tends to maintain the blood volume of the first bag at a predetermined point for a particular blood drainage rate such that the return blood flow rate is held at substantially the rate of the venous blood flow. The rate setting control may be manually varied by a supervising physician to directly change the rate of flow without shutting off the automatic system.
In accordance with another feature a reservoir is included for storing blood. The blood in the reservoir may be selectively admitted into the first drainage bag for increasing the total blood volume of the combined circulatory and cardio-pulmonary bypass system. A valve coupled tube may be used to tap off an excess quantity of blood if the flow exceeds predetermined levels .
Description of the Drawings Fig. 1 is a combined block and simplified broken away schematic diagram of an example of a blood flow controller in " accordance with the invention.
Detailed Description Referring to Fig. 1, in a preferred embodiment of cardio-pulmonary bypass system 10 in accordance with the invention, a collector means 12 is disposable below a blood withdrawal point on a patient for receiving a gravity fed venous blood flow from a human patient's circulatory system. A gas containment means or standpipe 14 coupled into the interior of the collector means extends vertically to a pressure responsive transducer 16 which is in operative relation to the interior at the upper end of the standpipe 14. The collector means 12 generally comprises a first collapsible bag 18 and a venous feed tube 20 coupled at an inlet of the collapsible bag 18. While the collapsible bag 18 and the venous feed tube 20 may be of various materials they here are of a surgical quality neoprene and are typically disposable units. The thickness of the collapsible bag 18, which is preferably transparent or translucent, is sufficient for it to accept a substantial volume of blood without danger of rupture or susceptibility to puncture from contact with foreign objects. The bag 18 is also, however, sufficiently pliable for its walls to readily conform to the interior blood volume, thereby sub-stantially eliminating an interior blood-gas interface and completely collapsing when all blood is removed. An outlet tube 19 at the top of the bag 18 can be closed by a clamp 21 when all air has been exhausted from the bag interior.
The standpipe 14 is preferably a rigid and transparent or translucent shaped tubular element of surgical quality. The standpipe 14 having a small interior volume in comparison with the interior volume of the first collapsible bag and having nominal blood levels therein, defines a confined gas volume 22 within a cylindrical chamber 23 and exerting a pressure through a sterility barrier 24 within the chamber 23 on the transducer 16. An increase of blood flow into the first collapsible bag 18 causes a distention of the bag 18 and thereby causes the blood level in the standpipe 14 to increase, reducing the confined gas volume 22. A reduction of the confined gas volume 22 causes an increase in the pressure applied through the sterility barrier 24 to the transducer 16. Small fractional changes in the blood flow rate into the collapsible bag 18, manifested by small fractional volume changes of blood in the collapsible bag 18 causes large fractional changes in the pressure of the confined gas volume 22. Thus the combination of the collection means 12, the standpipe 14 and the transducer 16 provide a highly sensitive means of measuring and indicating changes in the venous flow rate.
While the transducer 16 provides a signal related to a blood flow rate from the patient into the collapsible bag 18, this signal is not necessarily related to the signal which would be obtained if, for example, a patient's central venous pressure were monitored. The applicant's invention tends to provide a more accurate indication of venous flow rate since a patient's blood pressure may vary with changes in blood volume in the patient's circulatory system and with other parameters.
Revitalization or oxygenation means 28 is provided for continuous revitalization of the blood including the oxygen transfer to oxygen deficient blood and the warming of blood which has been partially cooled since removal from the patient. The oxygenation means 28 generally comprises an oxygenation pump 30 driven by a pump motor 32 coupled thereto. The oxygenation pump 30 is cou led to a membrane ox enator and heat exchan er 34 in series fashion, with the oxygenation pump 30 forcing blood througi the membrane oxygenator and heat exchanger 34. The pump motor 32 for the oxygenation pump 30 may be a roller blood pump in which blood is carried between a membrane and a surface defining a cylindrical chamber by rollers rotating and bearing on the mem-brane and against the surface.
A second collapsible bag 36 comparable to the first bag 18 is air evacuable and is preferably translucent or trans -parent. Flow through the oxygenation means 28 is transported to th collapsible bag 36 via a conduit 37 to provide generally a con-tinuous supply of freshly revitalized (i.e. oxygenated and warmed) blood to the second collapsible bag 36. The second collapsible bag 36 also helps to dampen or buffer uneven or pulsating flows of blood returned to the patient by way of a main pump 38. For positive circulation under all conditions, the main pump 38 is constantly driven at a slightly slower rate than the oxygenation pump 30 so that the main pump 38 does not operate without a blood flow supply.
Although two collapsible bags 18, 36 are described, it should be noted that a single partitioned bag may be used in accordance with this invention. The collapsible nature of the bags, besides limiting blood-gas interfaces, helps prevent a massive air embolism. Should blood in either bag 18 or 36, for some reason, be emptied and collapse occur, air which could enter through leaks in the cardiopulmonary bypass system 10 are prevented from being pumped into the patient's circulatory system.
A recirculation path is defined by a tube 39 coupling blood from the second bag 36 to the first bag 18, providing pressure relief to equalize pressure between the two bags 18, 36. Excess pressure would tend to be present in the second collapsible bag 36 in the absence of the recirculation path, because of the faster pump rate of the oxygenation pump 30 with respect to the main pump 38.
The main pump 38 is preferably a roller blood pump coupled to the second collapsible bag 36 for returning the oxygenated and warmed blood to the patient's circulatory system. The main pump 38 maintains a blood flow rate invariant with respect to a varying impedance or load of the human circulatory system as experienced by the pump 38, despite the fact that the impedance or load provided by the patient's circulatory system varies with the patient's physical state. For example, a constriction in the patient's circulatory system causes an increased impedance, yet blood is returned to the patient at a rate independent of that physical state.
A variable speed main pump motor 40 coupled to the main pump 38 drives the pump 38 at a desired controllable blood flow rate in response to a signal fed from controller means or a rate setting control 42. The rate setting control 42 may simply be an amplifier circuit providing an error signal tending to drive the variable speed pump motors at a rate equal to the venous blood flow. A preferred embodi-ment given by way of example provides a rate setting control 42 comprising an amplifier circuit 44, a servo motor 46, a speed reducer 48 coupled to the servo motor, a variable impedance or a potentiometer 50 mechanically coupled to the speed reducer 48 and a control knob 52 on the potentiometer shaft. Rate setting control 42 is responsive to a signal from the transducer 16 to provide the variable speed pump motor 40 with a signal from the potentiometer 50, which pump 38 at a flow rate corresponding to the blood volume in the collapsible bag 18. The blood volume in the collapsible bag 18 is maintained at a predetermined level such that the return blood flow rate is held substantially equal to the venous blood flow. The control knob 52 coupled to the potentiometer 50 can be used to manually override the rate setting control 42 to exercise supervisory control of the flow rate of the main pump 38.
The amplifier circuit 44 amplifies a bipolar null referenced signal from the transducer 16 to provide a signal sufficient to drive the servo motor 46. This signal is bipolar in that it may represent deviations from a null in either of two directions corresponding to either an increase in pressure exerted on the transducer 16 by the confined gas volume 22 or a decrease in pressure exerted by the confined gas volume 22. In setting up the system the pressure within the confined gas volume 22 may be equalized at ambient by a closeable outlet (not shown) in the cylinder 23, the outlet being shut when a desired blood level is reached in the standpipe 14. The servo motor 46 rotates in accordance with the polarity of the transducer signal tending to rotate the potentiometer 50 in accordance with the blood volume in the collapsible bag 18, as sensed by the transducer 16.
The speed reducer 48 may be a gear reduction system coupled between the servo motor 46 and the potentiometer 50, reducing the angular rotation of the potentiometer 50 with respect to the angular rotation of the servo motor 46 thereby providing an adjustable gain in the system. Gain is adjusted to allow time for changes in the pump rate of the main pump 38 to influence blood volume changes sensed by the transducer and further rotation of the servo motor without excessive overtravel speed of the variable speed pump motor 40 which in turn deter-mines the flow rate of the main pump 38. An adjustable re- sistance 54 in the motor 40 energizing circuit permits further adjustment to maintain a pump rate through the oxygenation pump 30 in excess of that through the main pump 38, such that a flow is recirculated back from the second collapsible bag 36 to the first bag 18 and the main pump 38 does not operate without a blood supply.
Dial indicia 53 juxtaposed adjacent the control knob 52 indicates the instantaneous rate at which the main pump 38 is being driven. The knob 52 may be manually rotated by overcoming the torque supplied by the servo motor 46 through the speed reducer 48. A slip clutch or a friction coupling between the speed reducer 48 and the potentiometer 50 is suitable for a motor 46 of greater torque, but this arrangement would not comparably restore the knob 52 to the proper setting when released.
An outlet tube 56 whose exterior surface is hermetically joined to the bag 36 can be closed by a clamp 57 to permit ex-haustion of interior air in the same fashion as the first bag 18.
A reservoir 58 is provided for receiving and storing an excess quantity of blood from the cardiopulmonary bypass system 10 and for increasing the volume of the blood in the cardio-pulmonary bypass system 10 by releasing such blood to the second bag 36 through a valve 59. A valve 60 in the conduit from the main pump 38 may be used to tap off blood from the cardiopulmonary bypass system 10. The valves 59, 60 used to add blood to the reservoir 58 and to release blood to the cardiopulmonary bypass system 10 may be manually actuable or may be of a type actuable by an electrical signal. For example, a perfusion flow servo system is described in the Turina et al. article in the March cardiotomy tube (not shown) may also be coupled into the reservoir" 58 to provide a blood source to the reservoir 58. The cardiotomy line is used to remove blood which collects adjacent severed veins and arteries resulting from incisions during an operation. The blood, having been suctioned off from the patient, is in a frothy condition and a debubbler (not shown) is typically used to reduce the frothy condition of the blood before it enters the reservoir 58.
To review the operation of the cardiopulmonary bypass system 10, the first collapsible bag 18 is generally disposed at a level beneath that of the patient so as to promote a gravity blood feed. Initially, blood is added to the first collapsible bag 18 with the bag clamps 21, 57 released. Ambient air pressure is established in the interior volume 22 and the transducer 16 by opening a valve (not shown) or disconnecting the standpipe 14 from the cylinder 23. Blood is added until the blood level in the standpipe 14 reaches a reference or priming level 62, after which the standpipe 22 is then reconnected to the sterility barrier 24 and the transducer 16. Thus the pressure in the confined volume 22 is initially equalized with respect to ambient.
Air that is present in the first and second collapsible bags 18, 36 is forced out, either manually or by filling the bags 18, 36, and the outlets 19, 56 are then closed by the clamps 21, 57. The blood air interfaces within the bags 18, 36 are thus minimized.
Venous blood flows under gravity into the first collapsible bag 18, whose volume then varies in accordance with the rate of blood flow therethrough. This volume establishes the blood level in the tandpipe 14, and as previously described fractional changes in the blood volume within the bag 18 cause much larger variations in the pressure exerted on the transducer 16. Though the transducer 16 signal is generally referenced to ambient pressure, an inverted U-tube arrangement (not shown) may be used to provide a negative pressure head so that the transducer may be arbitrarily oriented where the level of the collector means 12 varies from the position depicted in the embodiment of Fig. 1 and is, for example, disposed closer to the level of the patient.
The transducer 16 signal is applied to the amplifier circuit 44, providing an energizing signal to the servo motor 46} which rotates at a rate determined by signal amplitude and in a direction determined by polarity. Through the speed reducer 48, motor rotation turns the potentiometer 50 in a corresponding direction at a slower speed, also rotating the control knob 52 so that the blood flow rate may be read off the dial 53. As main pump 38 speed is adjusted by the motor 40 controlled by the potentiometer 50 setting, the blood level is returned toward the null position 62, slowing down or reversing the servo motor 46. Note that the pump motor 40 can continue to operate at or near a substantially constant speed and that the sys tem is stablized by gain adjustment at the speed reducer 48 although other means might also be used.
Blood from the first collapsible bag 18 is pumped through the revitalization or oxygenation means 28, by the oxygenation pump 30, which provides sufficient pressure to drive the blood through the membrane oxygenator and heat exchanger 34 and to the second collapsible bag 36. Because the oxygenation pump motor 32 speed is also determined by the potentiometer 50 setting, the oxygenation pump 30 pumps blood at a flow rate in excess of the flow rate of the main pump 38 as determined by the setting of the adjustable resistor 54. Excess pressure developed by the oxygenation pump 30 within the second collapsible bag 36 is relieved via the tube 39 which serves as a recirculation path. Blood from the second collapsible bag 36 is then pumped by the main pump 38 to the patient's circulatory system.
It is important to alert a physician to the existence of a low blood volume condition in a patient. This condition may represent internal hemorrhaging and may require that an additional quantity of blood be introduced into the total system. A physician or assistant, alerted to such a condition may now increase the circulating blood volume by opening the reservoir valve 59, thereby allowing blood to flow into the second collapsible bag 36. Also, or alternatively, the physician may manually override the knob 52, thereby in-creasing the flow rate of the main pump 38 to the human cir-culatory system. It should be recognized that such an increase in the return flow rate without replenishment can only be carried on for a limited period of time without collapse of the bags 18 and 36.
Thus, a simple, accurate and sensitive cardiopulmonary bypass system for receiving a variable rate gravity fed venous flow from a human circulatory system, revitalizing the blood and returning it to the circulatory system at a rate substantially equal to the venous flow rate has been described which is volume alterable and provides means for reducing degrading blood gas interfaces .
While the invention has been particularly shown and described and with reference to a preferred embodiment thereof, it will be understood by those skilled in the art that various

Claims (1)

1. A cardiopulmonary bypass system for receiving a variable rate gravity fed venous blood flow from a human culatory revitalizing the blood and returning the blood to the circulatory system at a flow rate equal to the gravity fed blood flow a first collapsible bag disposable below a withdrawal point coupled to receive a gravity ed flow of blood at an the collapsible bag being at least tially with blood and substantially without a the collapsible having a sufficient flexibility a collapse of the bag esulting from an emptying of blood therein inhibits a suction from occurring at the a second collapsible recirculation path moans for blood from the second collapsible bag to the first collapsible revitalizing means coupled between the and second collapsible for continuously oxygenating and warming blood from the first bag and transporting the oxygenated and warmed blood to the second main pump means coupled to the second bag for delivering a blood flow from the second bag to a human circulatory system at a te controlled by a control signal applied blood volume transducer means coupled to the bag providing a signal related to the blood volume in the first and controller means responsive to the blood volume dicfition for supplying a control signal to the main If pump means to drive the main pump means at a rate which tends to the blood volume of the first bag at a predetermined level such that the return blood flow is held substantially equal to the blood invention set forth in Claim 1 and in which the first collapsible bag volume is determined by the blood therein and including gas containment means coupled to said fir st bag and said tr nsducer means and nominal blood levels and an interior volume small in comparison with the interior volume of the collapsible said containment means defining a confined the within which acts on the transducer means such that blood flow rate changes into the first collapsible bag manifested by blood volume changes of the bag result in fractional changes in the confined gas volume and subsequent pressure changes that are much amplified with respect to the fractional blood changes of the The invention as set forth in Claim 2 in which said blood volume transducer means is coupled to the first container by a vertically extending standpipe having a small interior volume in comparison with the interior volume of said first said standpipe being positioned to prevent blood from the first container from coming into contact with said The invention as set forth in Claim 2 and in which the transducer the gas containment means and the collapsible bag define a closed system such that when the gas containment means is exposed to ambient air pressure and the system is brought to a reference the closing of the system thereby defines a the am set forth in 1 and further prising rate setting control means tending to maintain a return blood flow rate equal to venous rate means manually overriding the rate setting The invention as set forth in Claim and in which the means a oxygenator pump and heat exchanger coupled in series f said oxygenato pump including means responsive to the flow of the main pump for maintaining the flow rate of the pump at a rate greater than that of the main such that a flow is recirculated from said second bag to said first bag and main pump does not operate without a blood flow In a cardiopulmonary system of the type having a first container for receiving a blood a second container for receiving a revitalised blood flow from the first blood treatment apparatus and an auxiliary pump coupled between the first and second containersj a path for coupling blood from the second container to the first and a main pump coupled to the second container for providing a blood flow to a human cardiovascular the combination therewith transducer means responsive to a blood volume in the first means coupled between the main pump and the auxiliary pump for driving the auxiliary pump at a rate greater than that of the main pumpf and means for driving the main pump at a rate related to blood volume responsive signals received from said transducer The as set forth in Claim 7 and further a reservoir for storing fluid at a level than that of a fluid in first means coupled between the reservoir and the first tainer for a flow the reservoir to said and for selectively admitting a fluid from the reservoir to the first For the insufficientOCRQuality
IL46174A1974-01-211974-12-03Cardiopulmonary bypass systemIL46174A (en)

Applications Claiming Priority (1)

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US435223AUS3890969A (en)1974-01-211974-01-21Cardiopulmonary bypass system

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IL46174A0 IL46174A0 (en)1975-03-13
IL46174Atrue IL46174A (en)1977-05-31

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US (1)US3890969A (en)
JP (1)JPS50103199A (en)
AU (1)AU474712B2 (en)
BE (1)BE824319A (en)
CA (1)CA1042747A (en)
DE (1)DE2501552A1 (en)
FR (1)FR2258191A1 (en)
GB (1)GB1485300A (en)
IL (1)IL46174A (en)
IT (1)IT1028478B (en)
LU (1)LU71627A1 (en)
NL (1)NL7500327A (en)
SE (1)SE7500593L (en)
ZA (1)ZA747871B (en)

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LU71627A1 (en)1975-06-17
GB1485300A (en)1977-09-08
US3890969A (en)1975-06-24
ZA747871B (en)1975-12-31
SE7500593L (en)1975-07-22
JPS50103199A (en)1975-08-14
AU474712B2 (en)1976-07-29
AU7628674A (en)1976-06-17
FR2258191A1 (en)1975-08-18
NL7500327A (en)1975-07-23
BE824319A (en)1975-05-02
IL46174A0 (en)1975-03-13
CA1042747A (en)1978-11-21
IT1028478B (en)1979-01-30
DE2501552A1 (en)1975-07-24

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