CA2228422A1 - Portable perfusion/oxygenation module having respiratory gas driven, mechanically linked dual pumps and mechanically actuated flow control valve for slow pulsatile cycling of oxygenated perfusate during in vitro conservation of viable transplant organs - Google Patents
Portable perfusion/oxygenation module having respiratory gas driven, mechanically linked dual pumps and mechanically actuated flow control valve for slow pulsatile cycling of oxygenated perfusate during in vitro conservation of viable transplant organs Download PDFInfo
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- CA2228422A1 CA2228422A1 CA002228422A CA2228422A CA2228422A1 CA 2228422 A1 CA2228422 A1 CA 2228422A1 CA 002228422 A CA002228422 A CA 002228422A CA 2228422 A CA2228422 A CA 2228422A CA 2228422 A1 CA2228422 A1 CA 2228422A1
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- Prior art keywords
- chamber
- perfusate
- oxygen
- flow communication
- piston
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0236—Mechanical aspects
- A01N1/0242—Apparatuses, i.e. devices used in the process of preservation of living parts, such as pumps, refrigeration devices or any other devices featuring moving parts and/or temperature controlling components
- A01N1/0247—Apparatuses, i.e. devices used in the process of preservation of living parts, such as pumps, refrigeration devices or any other devices featuring moving parts and/or temperature controlling components for perfusion, i.e. for circulating fluid through organs, blood vessels or other living parts
Abstract
A portable perfusion/oxygenation module (10) includes respiratory gas driven dual positive displacement pumps (22, 24) coupled to a stacked membrane oxygenator unit (16) for perfusion fluid oxygenation, a valving manifold (26) to control perfusate flow direction coupled to an organ chamber (18) designed to enable easy installation of organ and maintenance of intra and extra organ fluid pressure. The perfusion/oxygenation apparatus requires no electrical power, is compact with the total weight being less than 50 pounds. With low weight and low flow rate of gas required to pump the perfusate, the oxygen supply is capable of sustaining pumping operation for 24 hours without gas cylinder change. No movable membranes, diaphragms or electrical power are required to deliver oxygenated perfusate.
Description
TITLE: PORTABLE PERFUSION/OX~GENATION MODULE HAVING
RESPIRATORY GAS DR~VEN, MECHANICALL~ LINKED
DUAL PUMPS AND MECHANICALLY ACTUATED FLOW
CONTROL VALVE FOR SLOW PULSATILE CYCLING OF
OXYGENATED PERFUSATI~ DURING IN VITRO
CONSERVATION OF VL~BLE TRANSPLANT ORGANS
Field of the Invention The present invention is related generally to organ preservation, and in particular to highly portable, nonelectric perfusion a~pal~lus for ~t1mini~tering a chilled, oxygenated nutrient solution through the vascular bed of an organ following excision of the organ.
Background of the Invention The ability to maintain organs by gravity-fed oxygenated perfusion fluids was described as early as 1907 by Locke. Perfilsion of oxygenated, balanced salt solutions COI~t;.;..;~.g sugars to meet energy requirements was shown to be superior to earlier perfusion systems where no sugars nor oxygenation was employed. Living hearts have been m~int:~ined viable for 24 hours using those early systems. Preservation of hearts for 0 subsequent transplantation into a recipient animal was also described in literature in 1960 as was the benefit of chilling the organs to 40~C in the storage condition.
The art and science of organ transplantation has developed rapidly since 1960, duc largely to improved methods of suppressing immune rejection of the transplanted organ by the transplant recipient. Presently, donor organs are collected under sterile conditions and 5 are transported to the operating room of a designated base facility where the transplant recipient is standing by. Transportation of the organ is done using portablc insulated containers kept at 40~C by blocks of ice, the organ itself being suspended in a container bathed by the balanced, chilled solution. However, perfusion of fluid through the vessels or cavities of the organ is not practiced nor is oxygenation of the solutions, although the value 5 of such procedures is established and widely recognized. Failure to apply these preferred methods is due to the excess quantity of oxygen required to circulate oxygenated fluid through the pressure dependent perfusion pumps.
Practical use of oxygenated perfusion requires that the organ transport apparatus be self-contained, pump for a minimum of ~4 hours and have compact size and low weight 10 so that one person can carry the entire apparatus unassisted. Its size should allow ready transport in standard vehicles such as small cars, helicopters, and jet aircraft. Since fluid oxygenation and organ perfusion are not presently used, the distance between donor and recipient is severely restricted as unperfused hearts progressively deteriorate. Four hours is regarded as the upper limit that a viable organ can be transplanted with a margin of anticipated success.
The ability to transport perfused and oxygenated organs over longer distances and/or for longer times would significantly improve the successful use of donor organs because (l ) organs would be in better physiological condition; (2) a larger selection of donor organs might become available; (3) time for better donor matching could influence better 2 o organ acceptability; (4) potential recipients might not have to be restricted to a base site; (5) surgical teams could have more predictable scheduling; (6) recipients of better quality organs would likely have a shorter clinical recovery and thus better well-being as well as cost saving; (7) a world-wide network of donors and recipients would be feasible.
The use of perfused, oxygenated and nutrient-balanced salt solutions at a reduced 2 5 temperature enhances the viability of the transplant organ in several ways: lowering of the perfusion fluid and organ temperature lowers the metabolic activity of the organ's cells and hence reduces the demand for physiologic oxygen levels and consumption of nutrients.
Reduction in cell metabolism also reduces the rate of production of by-products of metabolism such as C02 and lactic acid, thus further reducing tissue damage and stabilizing 3 o perfusate pH and osmotic balance. Lowering of the temperature reduces the demand for , oxygen and hence protects against inadequate oxygen levels that could result in ischemic tissue. In whole blood perfusate, oxygen transport is enhanced as a conse~uence of the hemoglobin in red blood cells serving to load, transport, and unload the oxygen in tissues of lower oxygen concentration.
Since perfusion fluids typically do not contain red blood cells, o~ygen transportation is a function of the direct solubility of the gas phase (oxygen) in the perfusate solution, also being dependent upon the partial pressure of 'the gas phase driving gas in the llquid perfusate. Hence, s~ f~ctory oxygen transport is achieved by exposing the perfusate to a gas phase under pressure, the pressure available being limited by the design of the o oxygenating chamber and also by the limits of perfusion pressure that- can be applied within the vessels of the perfused organ without c~ in~ damage. Because of the low oxygen demand of chilled tissue, the solubility of oxygen in water under low partial pressure is adequate to supply celltissue needs for maintenance oxygen levels.
Description of the Prior Art lHypothermic perfusion devices with oxygenation potential are known in the art and have been shown to work in experimental settings where transport of the apparatus is not needed. None of the conventional models, however, meet the requirements of a kansport device that is readily portable and sp~nng of oxygen consumption. For example, Doerig U.S.
Patent 3,914,954 describes an electrically driven ~ a~ s in which the perfusate is exposed 2 o to atmosphere thus breaking a sterility barrier, that must be operated upright, and consumes oxygen at high rates and is heavy. Requirement for electrical power in an oxygen-rich container and the availability of portable electrical power limit the practicality of this apparatus.
O'Dell and Gunegin Patent 5,362,622, Patent 5,385,821 and O'Dell Patent 5,356,77~ describe an organ perfusion system that employs either a fluidic logic device or a gas pressure driven ventilator pump to cyclically deliver gas to a sealed chamber connected to the top of the canister containing the organs. Cyclical, delivery of gas under pressure to the upper sealed chamber serves to displace a semi-permeable membrane mounted between the gas cllamber and the fluid cont5~ining organ canister. Cyclical membrane displacement se~ves to transduce the gas pressure into fluid displacement on 'the opposite side, thus providing flow of the perfusate solution.
The membrane is selected for its permeability to gas but not to water, permitting oxygen or other gas mixtures to be driven through the membrane into the perfusate or alternatively to vent C02 from the perfusate. The intent of such membrane pump devices was to provide a system that used no electricity, used low gas pressure and volumes to achieve perfusate flow, had few moving parts, provided adequate perfusate oxygenation, that could be operated in non-upright positions, that isolated the organ and perfusate from atmosphere, and as a total package, was of compact size and reduced weight to perrnit portability.
0 Although these designs have proved fimctional in experimental settings where portability was not necessary, these membrane pumps failed to meet the criteria claimed by the developers. For example, the transducing permeable membrane re~uires large volumes of gas to transduce the energy into fluid movement, with each cycle requiring several ml of gas to acbieve a fluid displacement of 30-60 ml/stroke. Extrapolation of these performance parameters extended to multiple cycle time periods show that. three or more large capacity cylinders would be required to sustain pumping without cylinder replacement for 24 hours.
These large capacity cylinders each weigh over 20 lbs and do not satisfy the need for a readily portable system. The membrane pump apparatus is further limited by the gas pressure and volume required to operate a ventilator pump, which is not repairable in the 2 o field.
The success of the membrane displacement pump design depends upon the membrane dynamic work being repeatable for multiple cycles without tearing or being displaced from its margins, the results of which would be catastrophic loss of the perfusion function of the device. Available gas perrneable membranes are not built to possess 2 5 elastome1ic properties. The apparatus is further co~ ,ol,lised by a multiple clamping system for canister lid fixation and sealing, necessary to sustain pressure dir~lelllial for pumping, consisting of silastic gels, with no design provision to assure against co~ a,ll~ent leaks.
The canister flow design aLL~;,ll~L~ to pulse perfusate both within the perfused organ and around the outside of the organ in an ~LLe~ l to saturate the organ with freshly oxygen-3 o ated perfusate. This also increases the demand for volumes of oxygen that are needed to WO 97/45~;27 CA O 2 2 2 8 4 2 2 19 9 8 - O 2 - O 2 PCT/US97/09000 saturate the fluid ~athing the organ. This procedure has no physiologic basis since the normal routes of tissue oxygenation are achieved by oxygen diffusion outwardly f rom the organ's vascular bed rather than inwardly through the outer capsule. Since the canister loses ~02, it also loses the added oxygen, the net result being an apparatus whose design is s wasteful of transportable gas.
Further, no provisions are made for connecting the donor organ to vessels of various sizes as would be experienced intransporting organs from pediatric to adult clinics.
Further, since the perfused organ vessels and the outside of the organ are exposed to pressurized perfusate, the outer pressure resists expansion of the perfused vessels and offers a flow resistance to the perfusate within the vessels. Although this could be regarded as a safety margin against overexpansion of the vessels, it also introduces the danger that smaller vessels and tributaries could be obstructed, thus c~ ing small regions of ischemic tissue.
~ince the pulse volume and pressure can be controlled by the pump, introduction of such f low constraints is ill founded. ~llbsti~ltion of a fluidic logic device for a respirator pump does allow less gas/cycle to be used. ~Iowever, it is restrictive in that typical fluid logic devices are set to operate within defined gas ~les~ule ranges and preclude ready adjustment of f low rates, and being encased valving systems, are not built to allow repair if valving fails.
~ummary of the Invention 2 o The present invention provides an a~al~lus and method that fulf ills these ess~-n~
criteria, namely, the irate of oxygen lltili7~tion allows two 250 liter cylinders to supply at least twenty-four hours of perfusion time, the entire ~a~aLus its into a standard styrofoam ice chest, is readily portable by one person, uses a simple mechanical drive, and has been shown to maintain human and animal hearts for l 8 hours or more with no deleterious effect 2 s to the perfused and transplanted organ.
The perfusion ~al~us ofthe present invention utilizes dual positive displacementpumps having pistons interconnected in a push-push configuration. The positive displacement pistons aye stroked by pressurized oxygen, with liquid perfusate being pumped through an oxygenator and into the vascular bed of a donor organ during one piston power W O 97/45527 CA 02228422 1998-02-02 PCTrUS97/09000 ,. 6 stroke. Perfusate that drains from the donor organ is collected in a sealed container and rcturned to the perfusate pump reservoir in response to a power stroke by the other pump.
Pressurized oxygen from a portable supply is alternately directed to the pressurized gas chambers of the first and second pumps by a two port, double-throw flow control valve.
5 The outlet ports of the double-throw control valve are selected by an actuator arrn that is mechanically coupled to the commonly connected piston rods of the dual pumps. The supply port is switched between the outlet ports in response to shifting movement of the actuator arm.
The actuator arm is shifted forward and reverse in response to forward and reverse 0 stroking rrlovement of the commonly connected piston rods. The valve actuator arm is engagable by over-center toggle linkage actuators that are spring-biased for rapid shifting movement away from an overcenter neutral position in response to forward and reverse piston stroke movement.
According to this arrangement, the two-port, doublethrow control valve, dual 5 pistons and over-center toggle linkage operate in a free-rllnning, astable multi-vibrator mode of operation. In this free-running mode, the pistons stroke in a reciprocal push-push arrangement that continuously supplies oxygen to the oxygenator, while slowly discharging perfusate through the oxygenator and into the organ at a first pressure level corresponding approximately to systolic pressure during the first stroke, and then returning spent perfusate 20 collected in the organ container back into the peyfusate pump reservoir and into the oxygenator at a second pressure level corresponding approximately to diastolic pressure during the second stroke. Preferably, the inlet oxygen pressure to the pistons is adjusted to provide relatively slow charge and return, with systolic/diastolic pressure strokes cycling in the range of about l .5 to about 2 strokes per minute.
2 5 Brief Description of the Drawin~s The present invention may be better understood and its advantages will be ~,arellt to those skilled in the art by reference to the accompanying drawings wherein like reference numerals refer to like elements in the several figures, and wherein:
FIGURE 1 is a simplified hydraulic circuit diagram showing the interconnection :' 7 of 'the principal components of a portable per~usion apparatus of the present invention;
FIGURE 2 is an elevational view, partially broken away and partially in section,showing a donor organ suspended within an organ container and coupled to an oxygenator for receiving freshly oxygenated perfusate;
FIGURE 3 is a side elevational view thereof, with ice packs surrounding the organ container;
FIGURE 4 is a top plan view thereof;
FIGURE ~ is a simplified pneumatic and hydraulic diagram which illustrates the interconne:ction of dual, positive displacement pumps having piston rods commonly 0 connected in a push-push arrangement for charging the oxygenator with perfusate and returning spent perfusate to the primary pump;
FIGURE 6 is a top plan view of-the dual pump combination shown in FIGUR~
5, which illustrates details of a springbiased, over-center toggle linkage valve actuating apparatus; and, FIGUR~ 7 is a graph illustrating the time variation of systolic and diastolic pressure of oxygenated perfusate that is ~lmini~tered through the vascular bed of the organ shown in lFIGURE 2.
Detailed Description of the Preferred Embodiment Referring now to FIGURE 1 of the drawings, the combination perfusion/oxygena-2 o tion apparatus l O of the present invention provides chilled, oxygenated perfusate at a slow delivery rate for nourishing and conserving a viable, human heart 12. Although the exemplar~r embodiment features a human heart, other organs that have an identifiable vascular system for carrying blood with separate in-flow and out-flow vessels can be nourished and m~int~ined in a viable condition by the perfuming apparatus of the present invention, for example kidneys, livers, thyroids, lungs, intestines, pancreas reproductive organs, brains, spleens, as well as severed limbs and the like. The perfuming apparatus lO
can be used for conserving organs and body parts of test ~nim~l~ such as mice, rats, dogs and cats, provided that the vascular in-flow vessel of the animal organ is sufficiently large to attach onto a fluid conduit.
~eferring llOW to Figure 1, Figure 2, Figure 3, Figure 4 and Figure 5, the perfusion apparatus 10 of the present invention includes a paiy of compressed oxygen cannisters connected in parallel thereby defining a portable oxygen supply 14, an oxygenator assembly 16, an organ container 18 having a sealed chamber 20, a pneumatic actuator 22, a positive displacement pump 24, a flow control valve 26 and a mechanical switching assembly 28 for actuating the control valve 26.
The oxygen supply 14 is coupled to the control valve 26 through a pressure regulator 30, a supply conduit 32 and a float regulator 34. The compresse oxygen supply has a capacity of approximately 450 liters of respirable oxygen.
o Compressed oxygen is conducted -through the control valve to the pneumatic actuator, the positive displacement pump and the oxygenator. The oxygenator has first and second oxygenator compartments 36, 38 that are divided by first and second oxygen permeable membranes 40, 42, respectively, thereby defining an oxygen chamber 44 and a perfusate chamber 46 in the first oxygenator compar~ment 36, and defining an oxygen chamber 48 and a perfusate chamber 50 in the second oxygenator compament 38. Theoxygen chambers 44, 48 are connected in flow communication with each other and with an oxygen supply part 52 by a bore 54. The perfusate chambers 46,50 are connected in flow communication with each other by a bypass tube 56. The perfusate chamber is connected in flow communication with a perfusate supply port 58, and the perfilsate chamber 50 is cormected in ilow comunication with the sealed orgarl chamber 20 through a delivery tube 60. As oxygen flows across the membranes 40, 42, some of the oxygen is transferred across the membranes and is absorbed by the perfusate. The oxygenated perfusate 62 id discharged into the vascular bed of the organ 12, in this instance a human heart, through the aorta and into an artery that bypasses the aorta valve, into the capillary vessels that nourish the heart muscle tissue. The organ chamber is cooled by ice packs 64 that surround the organ container 18.
The pneumatic actuator has a cylindrical bore 66 and a piston 68 that moves axially through the bore, thereby defing a com~,t;ssed gas chamber 69. Likewise, the pump 24 has a cylindrical bore 70 and a piston 72 that is axially movable through the bore, thereby defining a compressed gas chamber 74 and a perfilsate chamber 76. A piston rod 76 g connects the pistons 68, 72 together fer eoneurrent stroking movement.
The eontrol valve 26 has a supply port S connneeted to the eompresed oxygen supply 14 and f irst and second outlet ports A,B coupled to the compressed gas chambers 69,76 of the pneumatic aetuator and the pump 24, respeetiely. An actuator arm 78 is coupled 5 to the eommon piston rod 76 for switehing the supply port S in flow eo uniea-tion with the first and seeond eontrol valve out-let ports A,B in response to forward and reverse stroking movement of the eommonly eonneeted pistons.
First and second supply conduits 80, 82 eonnect the outlet ports A,B in flow col~ unication with the compressed gas ehambers 69,76 of the pneumatic actuator and the lo pump, respeetively. A supply eonduit 82 eonneets the perfuseate reservoir ehamber 76 of the pump in f low eo~ lullieation with the perfusate chamber supply port 58, and a first return conduit 84 connects 'the sealed organ ehamber in f low co~ ication with the perfusate reservoir ehanber supply port 52. A second return eonduit 86 eormeets the organ ehamber in flow eull~nunieation with the oxygenator perfusate supply port 58. An oxygen 5 supply eonduit 88 and a supply eonduit 90 eonneet the oxygen supply port to the oxygenator.
RESPIRATORY GAS DR~VEN, MECHANICALL~ LINKED
DUAL PUMPS AND MECHANICALLY ACTUATED FLOW
CONTROL VALVE FOR SLOW PULSATILE CYCLING OF
OXYGENATED PERFUSATI~ DURING IN VITRO
CONSERVATION OF VL~BLE TRANSPLANT ORGANS
Field of the Invention The present invention is related generally to organ preservation, and in particular to highly portable, nonelectric perfusion a~pal~lus for ~t1mini~tering a chilled, oxygenated nutrient solution through the vascular bed of an organ following excision of the organ.
Background of the Invention The ability to maintain organs by gravity-fed oxygenated perfusion fluids was described as early as 1907 by Locke. Perfilsion of oxygenated, balanced salt solutions COI~t;.;..;~.g sugars to meet energy requirements was shown to be superior to earlier perfusion systems where no sugars nor oxygenation was employed. Living hearts have been m~int:~ined viable for 24 hours using those early systems. Preservation of hearts for 0 subsequent transplantation into a recipient animal was also described in literature in 1960 as was the benefit of chilling the organs to 40~C in the storage condition.
The art and science of organ transplantation has developed rapidly since 1960, duc largely to improved methods of suppressing immune rejection of the transplanted organ by the transplant recipient. Presently, donor organs are collected under sterile conditions and 5 are transported to the operating room of a designated base facility where the transplant recipient is standing by. Transportation of the organ is done using portablc insulated containers kept at 40~C by blocks of ice, the organ itself being suspended in a container bathed by the balanced, chilled solution. However, perfusion of fluid through the vessels or cavities of the organ is not practiced nor is oxygenation of the solutions, although the value 5 of such procedures is established and widely recognized. Failure to apply these preferred methods is due to the excess quantity of oxygen required to circulate oxygenated fluid through the pressure dependent perfusion pumps.
Practical use of oxygenated perfusion requires that the organ transport apparatus be self-contained, pump for a minimum of ~4 hours and have compact size and low weight 10 so that one person can carry the entire apparatus unassisted. Its size should allow ready transport in standard vehicles such as small cars, helicopters, and jet aircraft. Since fluid oxygenation and organ perfusion are not presently used, the distance between donor and recipient is severely restricted as unperfused hearts progressively deteriorate. Four hours is regarded as the upper limit that a viable organ can be transplanted with a margin of anticipated success.
The ability to transport perfused and oxygenated organs over longer distances and/or for longer times would significantly improve the successful use of donor organs because (l ) organs would be in better physiological condition; (2) a larger selection of donor organs might become available; (3) time for better donor matching could influence better 2 o organ acceptability; (4) potential recipients might not have to be restricted to a base site; (5) surgical teams could have more predictable scheduling; (6) recipients of better quality organs would likely have a shorter clinical recovery and thus better well-being as well as cost saving; (7) a world-wide network of donors and recipients would be feasible.
The use of perfused, oxygenated and nutrient-balanced salt solutions at a reduced 2 5 temperature enhances the viability of the transplant organ in several ways: lowering of the perfusion fluid and organ temperature lowers the metabolic activity of the organ's cells and hence reduces the demand for physiologic oxygen levels and consumption of nutrients.
Reduction in cell metabolism also reduces the rate of production of by-products of metabolism such as C02 and lactic acid, thus further reducing tissue damage and stabilizing 3 o perfusate pH and osmotic balance. Lowering of the temperature reduces the demand for , oxygen and hence protects against inadequate oxygen levels that could result in ischemic tissue. In whole blood perfusate, oxygen transport is enhanced as a conse~uence of the hemoglobin in red blood cells serving to load, transport, and unload the oxygen in tissues of lower oxygen concentration.
Since perfusion fluids typically do not contain red blood cells, o~ygen transportation is a function of the direct solubility of the gas phase (oxygen) in the perfusate solution, also being dependent upon the partial pressure of 'the gas phase driving gas in the llquid perfusate. Hence, s~ f~ctory oxygen transport is achieved by exposing the perfusate to a gas phase under pressure, the pressure available being limited by the design of the o oxygenating chamber and also by the limits of perfusion pressure that- can be applied within the vessels of the perfused organ without c~ in~ damage. Because of the low oxygen demand of chilled tissue, the solubility of oxygen in water under low partial pressure is adequate to supply celltissue needs for maintenance oxygen levels.
Description of the Prior Art lHypothermic perfusion devices with oxygenation potential are known in the art and have been shown to work in experimental settings where transport of the apparatus is not needed. None of the conventional models, however, meet the requirements of a kansport device that is readily portable and sp~nng of oxygen consumption. For example, Doerig U.S.
Patent 3,914,954 describes an electrically driven ~ a~ s in which the perfusate is exposed 2 o to atmosphere thus breaking a sterility barrier, that must be operated upright, and consumes oxygen at high rates and is heavy. Requirement for electrical power in an oxygen-rich container and the availability of portable electrical power limit the practicality of this apparatus.
O'Dell and Gunegin Patent 5,362,622, Patent 5,385,821 and O'Dell Patent 5,356,77~ describe an organ perfusion system that employs either a fluidic logic device or a gas pressure driven ventilator pump to cyclically deliver gas to a sealed chamber connected to the top of the canister containing the organs. Cyclical, delivery of gas under pressure to the upper sealed chamber serves to displace a semi-permeable membrane mounted between the gas cllamber and the fluid cont5~ining organ canister. Cyclical membrane displacement se~ves to transduce the gas pressure into fluid displacement on 'the opposite side, thus providing flow of the perfusate solution.
The membrane is selected for its permeability to gas but not to water, permitting oxygen or other gas mixtures to be driven through the membrane into the perfusate or alternatively to vent C02 from the perfusate. The intent of such membrane pump devices was to provide a system that used no electricity, used low gas pressure and volumes to achieve perfusate flow, had few moving parts, provided adequate perfusate oxygenation, that could be operated in non-upright positions, that isolated the organ and perfusate from atmosphere, and as a total package, was of compact size and reduced weight to perrnit portability.
0 Although these designs have proved fimctional in experimental settings where portability was not necessary, these membrane pumps failed to meet the criteria claimed by the developers. For example, the transducing permeable membrane re~uires large volumes of gas to transduce the energy into fluid movement, with each cycle requiring several ml of gas to acbieve a fluid displacement of 30-60 ml/stroke. Extrapolation of these performance parameters extended to multiple cycle time periods show that. three or more large capacity cylinders would be required to sustain pumping without cylinder replacement for 24 hours.
These large capacity cylinders each weigh over 20 lbs and do not satisfy the need for a readily portable system. The membrane pump apparatus is further limited by the gas pressure and volume required to operate a ventilator pump, which is not repairable in the 2 o field.
The success of the membrane displacement pump design depends upon the membrane dynamic work being repeatable for multiple cycles without tearing or being displaced from its margins, the results of which would be catastrophic loss of the perfusion function of the device. Available gas perrneable membranes are not built to possess 2 5 elastome1ic properties. The apparatus is further co~ ,ol,lised by a multiple clamping system for canister lid fixation and sealing, necessary to sustain pressure dir~lelllial for pumping, consisting of silastic gels, with no design provision to assure against co~ a,ll~ent leaks.
The canister flow design aLL~;,ll~L~ to pulse perfusate both within the perfused organ and around the outside of the organ in an ~LLe~ l to saturate the organ with freshly oxygen-3 o ated perfusate. This also increases the demand for volumes of oxygen that are needed to WO 97/45~;27 CA O 2 2 2 8 4 2 2 19 9 8 - O 2 - O 2 PCT/US97/09000 saturate the fluid ~athing the organ. This procedure has no physiologic basis since the normal routes of tissue oxygenation are achieved by oxygen diffusion outwardly f rom the organ's vascular bed rather than inwardly through the outer capsule. Since the canister loses ~02, it also loses the added oxygen, the net result being an apparatus whose design is s wasteful of transportable gas.
Further, no provisions are made for connecting the donor organ to vessels of various sizes as would be experienced intransporting organs from pediatric to adult clinics.
Further, since the perfused organ vessels and the outside of the organ are exposed to pressurized perfusate, the outer pressure resists expansion of the perfused vessels and offers a flow resistance to the perfusate within the vessels. Although this could be regarded as a safety margin against overexpansion of the vessels, it also introduces the danger that smaller vessels and tributaries could be obstructed, thus c~ ing small regions of ischemic tissue.
~ince the pulse volume and pressure can be controlled by the pump, introduction of such f low constraints is ill founded. ~llbsti~ltion of a fluidic logic device for a respirator pump does allow less gas/cycle to be used. ~Iowever, it is restrictive in that typical fluid logic devices are set to operate within defined gas ~les~ule ranges and preclude ready adjustment of f low rates, and being encased valving systems, are not built to allow repair if valving fails.
~ummary of the Invention 2 o The present invention provides an a~al~lus and method that fulf ills these ess~-n~
criteria, namely, the irate of oxygen lltili7~tion allows two 250 liter cylinders to supply at least twenty-four hours of perfusion time, the entire ~a~aLus its into a standard styrofoam ice chest, is readily portable by one person, uses a simple mechanical drive, and has been shown to maintain human and animal hearts for l 8 hours or more with no deleterious effect 2 s to the perfused and transplanted organ.
The perfusion ~al~us ofthe present invention utilizes dual positive displacementpumps having pistons interconnected in a push-push configuration. The positive displacement pistons aye stroked by pressurized oxygen, with liquid perfusate being pumped through an oxygenator and into the vascular bed of a donor organ during one piston power W O 97/45527 CA 02228422 1998-02-02 PCTrUS97/09000 ,. 6 stroke. Perfusate that drains from the donor organ is collected in a sealed container and rcturned to the perfusate pump reservoir in response to a power stroke by the other pump.
Pressurized oxygen from a portable supply is alternately directed to the pressurized gas chambers of the first and second pumps by a two port, double-throw flow control valve.
5 The outlet ports of the double-throw control valve are selected by an actuator arrn that is mechanically coupled to the commonly connected piston rods of the dual pumps. The supply port is switched between the outlet ports in response to shifting movement of the actuator arm.
The actuator arm is shifted forward and reverse in response to forward and reverse 0 stroking rrlovement of the commonly connected piston rods. The valve actuator arm is engagable by over-center toggle linkage actuators that are spring-biased for rapid shifting movement away from an overcenter neutral position in response to forward and reverse piston stroke movement.
According to this arrangement, the two-port, doublethrow control valve, dual 5 pistons and over-center toggle linkage operate in a free-rllnning, astable multi-vibrator mode of operation. In this free-running mode, the pistons stroke in a reciprocal push-push arrangement that continuously supplies oxygen to the oxygenator, while slowly discharging perfusate through the oxygenator and into the organ at a first pressure level corresponding approximately to systolic pressure during the first stroke, and then returning spent perfusate 20 collected in the organ container back into the peyfusate pump reservoir and into the oxygenator at a second pressure level corresponding approximately to diastolic pressure during the second stroke. Preferably, the inlet oxygen pressure to the pistons is adjusted to provide relatively slow charge and return, with systolic/diastolic pressure strokes cycling in the range of about l .5 to about 2 strokes per minute.
2 5 Brief Description of the Drawin~s The present invention may be better understood and its advantages will be ~,arellt to those skilled in the art by reference to the accompanying drawings wherein like reference numerals refer to like elements in the several figures, and wherein:
FIGURE 1 is a simplified hydraulic circuit diagram showing the interconnection :' 7 of 'the principal components of a portable per~usion apparatus of the present invention;
FIGURE 2 is an elevational view, partially broken away and partially in section,showing a donor organ suspended within an organ container and coupled to an oxygenator for receiving freshly oxygenated perfusate;
FIGURE 3 is a side elevational view thereof, with ice packs surrounding the organ container;
FIGURE 4 is a top plan view thereof;
FIGURE ~ is a simplified pneumatic and hydraulic diagram which illustrates the interconne:ction of dual, positive displacement pumps having piston rods commonly 0 connected in a push-push arrangement for charging the oxygenator with perfusate and returning spent perfusate to the primary pump;
FIGURE 6 is a top plan view of-the dual pump combination shown in FIGUR~
5, which illustrates details of a springbiased, over-center toggle linkage valve actuating apparatus; and, FIGUR~ 7 is a graph illustrating the time variation of systolic and diastolic pressure of oxygenated perfusate that is ~lmini~tered through the vascular bed of the organ shown in lFIGURE 2.
Detailed Description of the Preferred Embodiment Referring now to FIGURE 1 of the drawings, the combination perfusion/oxygena-2 o tion apparatus l O of the present invention provides chilled, oxygenated perfusate at a slow delivery rate for nourishing and conserving a viable, human heart 12. Although the exemplar~r embodiment features a human heart, other organs that have an identifiable vascular system for carrying blood with separate in-flow and out-flow vessels can be nourished and m~int~ined in a viable condition by the perfuming apparatus of the present invention, for example kidneys, livers, thyroids, lungs, intestines, pancreas reproductive organs, brains, spleens, as well as severed limbs and the like. The perfuming apparatus lO
can be used for conserving organs and body parts of test ~nim~l~ such as mice, rats, dogs and cats, provided that the vascular in-flow vessel of the animal organ is sufficiently large to attach onto a fluid conduit.
~eferring llOW to Figure 1, Figure 2, Figure 3, Figure 4 and Figure 5, the perfusion apparatus 10 of the present invention includes a paiy of compressed oxygen cannisters connected in parallel thereby defining a portable oxygen supply 14, an oxygenator assembly 16, an organ container 18 having a sealed chamber 20, a pneumatic actuator 22, a positive displacement pump 24, a flow control valve 26 and a mechanical switching assembly 28 for actuating the control valve 26.
The oxygen supply 14 is coupled to the control valve 26 through a pressure regulator 30, a supply conduit 32 and a float regulator 34. The compresse oxygen supply has a capacity of approximately 450 liters of respirable oxygen.
o Compressed oxygen is conducted -through the control valve to the pneumatic actuator, the positive displacement pump and the oxygenator. The oxygenator has first and second oxygenator compartments 36, 38 that are divided by first and second oxygen permeable membranes 40, 42, respectively, thereby defining an oxygen chamber 44 and a perfusate chamber 46 in the first oxygenator compar~ment 36, and defining an oxygen chamber 48 and a perfusate chamber 50 in the second oxygenator compament 38. Theoxygen chambers 44, 48 are connected in flow communication with each other and with an oxygen supply part 52 by a bore 54. The perfusate chambers 46,50 are connected in flow communication with each other by a bypass tube 56. The perfusate chamber is connected in flow communication with a perfusate supply port 58, and the perfilsate chamber 50 is cormected in ilow comunication with the sealed orgarl chamber 20 through a delivery tube 60. As oxygen flows across the membranes 40, 42, some of the oxygen is transferred across the membranes and is absorbed by the perfusate. The oxygenated perfusate 62 id discharged into the vascular bed of the organ 12, in this instance a human heart, through the aorta and into an artery that bypasses the aorta valve, into the capillary vessels that nourish the heart muscle tissue. The organ chamber is cooled by ice packs 64 that surround the organ container 18.
The pneumatic actuator has a cylindrical bore 66 and a piston 68 that moves axially through the bore, thereby defing a com~,t;ssed gas chamber 69. Likewise, the pump 24 has a cylindrical bore 70 and a piston 72 that is axially movable through the bore, thereby defining a compressed gas chamber 74 and a perfilsate chamber 76. A piston rod 76 g connects the pistons 68, 72 together fer eoneurrent stroking movement.
The eontrol valve 26 has a supply port S connneeted to the eompresed oxygen supply 14 and f irst and second outlet ports A,B coupled to the compressed gas chambers 69,76 of the pneumatic aetuator and the pump 24, respeetiely. An actuator arm 78 is coupled 5 to the eommon piston rod 76 for switehing the supply port S in flow eo uniea-tion with the first and seeond eontrol valve out-let ports A,B in response to forward and reverse stroking movement of the eommonly eonneeted pistons.
First and second supply conduits 80, 82 eonnect the outlet ports A,B in flow col~ unication with the compressed gas ehambers 69,76 of the pneumatic actuator and the lo pump, respeetively. A supply eonduit 82 eonneets the perfuseate reservoir ehamber 76 of the pump in f low eo~ lullieation with the perfusate chamber supply port 58, and a first return conduit 84 connects 'the sealed organ ehamber in f low co~ ication with the perfusate reservoir ehanber supply port 52. A second return eonduit 86 eormeets the organ ehamber in flow eull~nunieation with the oxygenator perfusate supply port 58. An oxygen 5 supply eonduit 88 and a supply eonduit 90 eonneet the oxygen supply port to the oxygenator.
Claims (6)
1. Perfusion apparatus of the type including a sealed chamber for administering oxygenated perfusate into an organ, an oxygenator having a perfusa-te supply port for receiving liquid perfusate and an oxygen supply port for receiving pressurized oxygen, characterized by:
a positive displacement pump having a compressed gas chamber and a perfusate reservoir chamber separated by a movable piston, a linear actuator having a compressed gas chamber a piston movable through the compressed gas chamber; a piston rod connecting the pump piston and the actuator piston together for concurrent stroking movement; a control valve having a supply port for receiving compressed oxygen from a supply and first and second outlet ports coupled to the compressed oxygen chambers of thepneumatic actuator and the perfusate pump, respectively, and an actuator arm coupled to the common piston rod for switching the supply port in flow communication with the first and second outlet control valve outlet ports in response to forward and reverse stroking movement of the commonly connected piston rods, respectively; first and second supply conduits connecting the first and second control valve outlet ports in flow communication with the oxygen chamber of the oxygenator; a supply conduit connecting the perfusate reservoir chamber of the pump in flow communication with the perfusate chamber of the oxygenator; a first return conduit connecting the sealed organ chamber in flow communication with the perfusate reservoir chamber of the pump; and a second return conduit connecting the sealed organ chamber in flow communication with the oxygenator perfusate chamber.
a positive displacement pump having a compressed gas chamber and a perfusate reservoir chamber separated by a movable piston, a linear actuator having a compressed gas chamber a piston movable through the compressed gas chamber; a piston rod connecting the pump piston and the actuator piston together for concurrent stroking movement; a control valve having a supply port for receiving compressed oxygen from a supply and first and second outlet ports coupled to the compressed oxygen chambers of thepneumatic actuator and the perfusate pump, respectively, and an actuator arm coupled to the common piston rod for switching the supply port in flow communication with the first and second outlet control valve outlet ports in response to forward and reverse stroking movement of the commonly connected piston rods, respectively; first and second supply conduits connecting the first and second control valve outlet ports in flow communication with the oxygen chamber of the oxygenator; a supply conduit connecting the perfusate reservoir chamber of the pump in flow communication with the perfusate chamber of the oxygenator; a first return conduit connecting the sealed organ chamber in flow communication with the perfusate reservoir chamber of the pump; and a second return conduit connecting the sealed organ chamber in flow communication with the oxygenator perfusate chamber.
2. Perfusion apparatus of the type having a sealed chamber for receiving an organ and an oxygenator having a perfusate supply port for receiving liquid perfusate, and an oxygen supply port for receiving pressurized oxygen, and a membrane for transferring the oxygen into the liquid perfusate, characterized in that:
said oxygenator having first and second oxygenation compartments, the first and second oxygenation compartments being divided by first and second oxygen permeable membranes, respectively, thereby defining a perfusate chamber and an oxygen chamber in each compartment, respectively, wherein the oxygen chambers are connected in flow communication with the oxygen supply port and the perf usate chambers are connected in flow communication with each other, the first perfusate chamber being connected in flow communication with the pefusate supply port and the second perfusate compartment being connected in flow communication with the sealed organ chamber.
said oxygenator having first and second oxygenation compartments, the first and second oxygenation compartments being divided by first and second oxygen permeable membranes, respectively, thereby defining a perfusate chamber and an oxygen chamber in each compartment, respectively, wherein the oxygen chambers are connected in flow communication with the oxygen supply port and the perf usate chambers are connected in flow communication with each other, the first perfusate chamber being connected in flow communication with the pefusate supply port and the second perfusate compartment being connected in flow communication with the sealed organ chamber.
3. Perfusion apparatus of the type including a sealed container for perfusing anorgan with liquid perfusate solution and an oxygenator having an oxygen chamber and a perfusate chamber for transferring oxygen from a supply of compressed oxygen to the perfusate solution before the perfusate solution is administered to the organ, characterized by:
first and second positive displacement pumps each having a compressed gas chamber and a reservoir chamber separated by a movable piston, the pistons of the first and second pumps each having piston rods commonly connected for concurrent stroking movement, a control valve having a supply port, first and second outlet ports and an actuator for selectively directing pressurized oxygen into the compressed gas chambers of the first second pumps, respectively, in response to shifting movement of the actuator, shifting apparatus coupled between the actuator and the commonly connected pistons for shifting the actuator in the direction of piston stroke movement, first and second power conduits connecting the first and second control valve outlet ports in flow communication with the compressed gas chambers of the first and second pumps, respectively, first and second supply conduits connecting the first and second control valve outlet ports in flow communication with the oxygen chamber of the oxygenator, a first return conduit connecting the oxygenator perfusate in flow communication with the pump perfusate reservoir chamber, and a second return conduit connecting the organ container chamber in flow communication with the pump perfusate reservoir chamber.
first and second positive displacement pumps each having a compressed gas chamber and a reservoir chamber separated by a movable piston, the pistons of the first and second pumps each having piston rods commonly connected for concurrent stroking movement, a control valve having a supply port, first and second outlet ports and an actuator for selectively directing pressurized oxygen into the compressed gas chambers of the first second pumps, respectively, in response to shifting movement of the actuator, shifting apparatus coupled between the actuator and the commonly connected pistons for shifting the actuator in the direction of piston stroke movement, first and second power conduits connecting the first and second control valve outlet ports in flow communication with the compressed gas chambers of the first and second pumps, respectively, first and second supply conduits connecting the first and second control valve outlet ports in flow communication with the oxygen chamber of the oxygenator, a first return conduit connecting the oxygenator perfusate in flow communication with the pump perfusate reservoir chamber, and a second return conduit connecting the organ container chamber in flow communication with the pump perfusate reservoir chamber.
4. Self-contained, portable perfusion apparatus comprising, in combination:
a portable supply of compressed gas;
first and second positive displacement pumps, each pump having a cylindrical bore, a piston movable through the cylindrical bore thereby dividing the cylindrical bore into a compressed gas chamber and a perfusate reservoir chamber, and a piston rod attached to the piston and projecting through the reservoir chamber of each pump, respectively, the piston rods being connected together for concurrent stroking movement;
a control valve having a supply port connected to the compressed gas supply, a first outlet port and a second outlet port, and an actuator for switching the supply port in f low communication with the f irst outlet part in response to shifting movement of the actuator to a first position, and for switching the supply port in flow communication with the second outlet port in response to shifting movement of the actuator to a second position;
shifting apparatus movably coupled to the control valve actuator arm and to the connected piston rods for shifting the actuator in the direction of piston stroking movement;
an organ container having a sealed chamber for receiving an organ;
an oxygenator assembly having an oxygen chamber, a perfusate chamber, an oxygen permeable membrane separating the oxygen chamber and the perfusate chamber, and a delivery tube connecting the perfusate chamber in flow communication with the organ chamber;
first and second power conduits connecting the first and second control valve outlet ports in flow communication with the compressed gas chambers of the first and second pumps, respectively;
first and second supply conduits connecting the first and second control valve outlet ports in flow communication with the oxygen chamber of the oxygenator;
a first return conduit connecting the organ chamber in flow communication with the pump perfusate reservoir chamber; and, a second return conduit connecting the organ chamber of the oxygenator in flow communication with the oxygenator perfusate reservoir chamber.
a portable supply of compressed gas;
first and second positive displacement pumps, each pump having a cylindrical bore, a piston movable through the cylindrical bore thereby dividing the cylindrical bore into a compressed gas chamber and a perfusate reservoir chamber, and a piston rod attached to the piston and projecting through the reservoir chamber of each pump, respectively, the piston rods being connected together for concurrent stroking movement;
a control valve having a supply port connected to the compressed gas supply, a first outlet port and a second outlet port, and an actuator for switching the supply port in f low communication with the f irst outlet part in response to shifting movement of the actuator to a first position, and for switching the supply port in flow communication with the second outlet port in response to shifting movement of the actuator to a second position;
shifting apparatus movably coupled to the control valve actuator arm and to the connected piston rods for shifting the actuator in the direction of piston stroking movement;
an organ container having a sealed chamber for receiving an organ;
an oxygenator assembly having an oxygen chamber, a perfusate chamber, an oxygen permeable membrane separating the oxygen chamber and the perfusate chamber, and a delivery tube connecting the perfusate chamber in flow communication with the organ chamber;
first and second power conduits connecting the first and second control valve outlet ports in flow communication with the compressed gas chambers of the first and second pumps, respectively;
first and second supply conduits connecting the first and second control valve outlet ports in flow communication with the oxygen chamber of the oxygenator;
a first return conduit connecting the organ chamber in flow communication with the pump perfusate reservoir chamber; and, a second return conduit connecting the organ chamber of the oxygenator in flow communication with the oxygenator perfusate reservoir chamber.
5. A self-contained, portable perfusion apparatus comprising, in combination:
a portable supply of compressed oxygen;
a sealed chamber for administering oxygenated perfusate into an organ;
an oxygenator having a perfusate supply port for receiving liquid perfusate and an oxygen supply port for receiving compressed oxygen;
a positive displacement pump having a compressed chamber and a perfusate reservoir chamber separated by a movable piston;
a pneumatic actuator having a compressed gas chamber and a piston movable through the compressed gas chamber;
a piston rod connecting the pump piston to the pneumatic actuator piston thereby providing concurrent stroking movement of the pistons;
a control valve having a supply port coupled to compressed oxygen supply and having first and second outlet ports coupled to the compressed oxygen chambers of the perfusate pump and the pneumatic actuator, respectively, and having an actuator arm coupled to the common piston rod for switching the supply port in flow communication with the first and second control valve outlet ports in response to forward and reverse stroking movement of the commonly connected pistons, respectively;
first and second supply conduits connecting the first and second control valve outlet ports in flow comiaunication with the oxygen chamber of the oxygenator;
a supply conduit connecting the pump perfusate reservoir chamber in flow communication with the oxygenator perfusate chambers;
a first return conduit connecting the sealed organ chamber in flow communication with pump perfusate reservoir chamber; and, a second return conduit connecting the sealed organ chamber in flow communication with the oxygenator perfusate chamber.
a portable supply of compressed oxygen;
a sealed chamber for administering oxygenated perfusate into an organ;
an oxygenator having a perfusate supply port for receiving liquid perfusate and an oxygen supply port for receiving compressed oxygen;
a positive displacement pump having a compressed chamber and a perfusate reservoir chamber separated by a movable piston;
a pneumatic actuator having a compressed gas chamber and a piston movable through the compressed gas chamber;
a piston rod connecting the pump piston to the pneumatic actuator piston thereby providing concurrent stroking movement of the pistons;
a control valve having a supply port coupled to compressed oxygen supply and having first and second outlet ports coupled to the compressed oxygen chambers of the perfusate pump and the pneumatic actuator, respectively, and having an actuator arm coupled to the common piston rod for switching the supply port in flow communication with the first and second control valve outlet ports in response to forward and reverse stroking movement of the commonly connected pistons, respectively;
first and second supply conduits connecting the first and second control valve outlet ports in flow comiaunication with the oxygen chamber of the oxygenator;
a supply conduit connecting the pump perfusate reservoir chamber in flow communication with the oxygenator perfusate chambers;
a first return conduit connecting the sealed organ chamber in flow communication with pump perfusate reservoir chamber; and, a second return conduit connecting the sealed organ chamber in flow communication with the oxygenator perfusate chamber.
6. A self-contained, portable perfusion apparatus comprising, in combination:
portable supply of compressed oxygen;
a positive displacement pump having a bore, a piston movable through the bore thereby dividing the bore into a compressed gas chamber and a perfusate reservoir chamber;
a pneumatic actuator having a bore and a piston movable through the bore thereby defining a movable boundary for the compressed gas chamber;
a piston rod attached to the pump piston and the actuator piston thereby providing concurrent piston stroking movement;
a control valve having a supply port connected to the portable oxygen supply and having first and second outlet ports coupled to the compressed oxygen chambers of the pneumatic actuator and the perfusate pump; respectively;
the control valve having a actuator arm for switching the supply port in flow communication with the first valve outlet port in response to shifting movement of the actuator arm to a first position, and for switching the supply port in flow communication wi-the the second valve outlet port in response to shif ting movement of the actuator arm to a second position;
shifting apparatus movably coupled to the control valve actuator arm and to the common piston rod f or shifting the actuator arm to the first position and to the second position in response to forward and reverse stroking movement of the commonly connected pistons, respectively;
a oxygenator having an oxygen chamber, a perfusate chamber and an oxygen permeable membrane for transferring oxygen into the perfusate chamber;
a sealed container for administering oxygenated perfusate into an organ contained within the sealed organ chamber;
power conduits connecting the first and second control valve outlet ports in flow communication with the compressed gas chambers of the pneumatic actuator and perfusate pump, respectively;
supply conduits connecting the first and second valve outlet ports in flow communication with the oxygen chamber of the oxygenator;
a supply conduit connecting the pump perf usate reservoir in flow communication with the oxygenator perfusate chamber; and first and second return conduits connecting the organ chamber in flow communication with the pump perfusate reservoir and the oxygenator perfusate chamber, respectively.
a sealed chamber for administering oxygenated perfusate into an organ;
an oxygenator having perfusate supply port for receiving liquid perfusate and an oxygen supply port for receiving compressed oxygen;
a positive displacement pump having a compressed gas chamber and a perfusate reservior chamber separated by a movable piston;
a pneumatic actuator having a compressed gas chamber and vent chamber separated by a movable piston;
the pump piston and the actuator piston having piston rods connected together for concurrent stroking movement;
a control valve having a supply port for receiving compressed oxygen from the portable supply and first and second outlet ports coupled to the compressed oxygen chamber of the linear actuator and the perfusate pump, respectively, and an actuator arm coupled to the commonly connected piston rods for switching the supply port in flow communication with the first and second control valve outlet ports in response to forward and reverse stroking movement of the commonly connected piston rods, respectively;
first and second supply connecting the first and second control valve outlet ports in flow communication with the oxygen chamber of the oxygenator;
a supply conduit connecting the pump reservoir chamber in flow communication with the oxygenator perfusate chamber;
a first return conduit connecting the sealed organ chamber in flow communication with the pump reservoir chamber; and a second return conduit connecting the sealed organ chamber in flow communication with the oxygenator perfusate chamber.
portable supply of compressed oxygen;
a positive displacement pump having a bore, a piston movable through the bore thereby dividing the bore into a compressed gas chamber and a perfusate reservoir chamber;
a pneumatic actuator having a bore and a piston movable through the bore thereby defining a movable boundary for the compressed gas chamber;
a piston rod attached to the pump piston and the actuator piston thereby providing concurrent piston stroking movement;
a control valve having a supply port connected to the portable oxygen supply and having first and second outlet ports coupled to the compressed oxygen chambers of the pneumatic actuator and the perfusate pump; respectively;
the control valve having a actuator arm for switching the supply port in flow communication with the first valve outlet port in response to shifting movement of the actuator arm to a first position, and for switching the supply port in flow communication wi-the the second valve outlet port in response to shif ting movement of the actuator arm to a second position;
shifting apparatus movably coupled to the control valve actuator arm and to the common piston rod f or shifting the actuator arm to the first position and to the second position in response to forward and reverse stroking movement of the commonly connected pistons, respectively;
a oxygenator having an oxygen chamber, a perfusate chamber and an oxygen permeable membrane for transferring oxygen into the perfusate chamber;
a sealed container for administering oxygenated perfusate into an organ contained within the sealed organ chamber;
power conduits connecting the first and second control valve outlet ports in flow communication with the compressed gas chambers of the pneumatic actuator and perfusate pump, respectively;
supply conduits connecting the first and second valve outlet ports in flow communication with the oxygen chamber of the oxygenator;
a supply conduit connecting the pump perf usate reservoir in flow communication with the oxygenator perfusate chamber; and first and second return conduits connecting the organ chamber in flow communication with the pump perfusate reservoir and the oxygenator perfusate chamber, respectively.
a sealed chamber for administering oxygenated perfusate into an organ;
an oxygenator having perfusate supply port for receiving liquid perfusate and an oxygen supply port for receiving compressed oxygen;
a positive displacement pump having a compressed gas chamber and a perfusate reservior chamber separated by a movable piston;
a pneumatic actuator having a compressed gas chamber and vent chamber separated by a movable piston;
the pump piston and the actuator piston having piston rods connected together for concurrent stroking movement;
a control valve having a supply port for receiving compressed oxygen from the portable supply and first and second outlet ports coupled to the compressed oxygen chamber of the linear actuator and the perfusate pump, respectively, and an actuator arm coupled to the commonly connected piston rods for switching the supply port in flow communication with the first and second control valve outlet ports in response to forward and reverse stroking movement of the commonly connected piston rods, respectively;
first and second supply connecting the first and second control valve outlet ports in flow communication with the oxygen chamber of the oxygenator;
a supply conduit connecting the pump reservoir chamber in flow communication with the oxygenator perfusate chamber;
a first return conduit connecting the sealed organ chamber in flow communication with the pump reservoir chamber; and a second return conduit connecting the sealed organ chamber in flow communication with the oxygenator perfusate chamber.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/652,696 | 1996-05-29 | ||
| US08/652,696 US5965433A (en) | 1996-05-29 | 1996-05-29 | Portable perfusion/oxygenation module having mechanically linked dual pumps and mechanically actuated flow control for pulsatile cycling of oxygenated perfusate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2228422A1 true CA2228422A1 (en) | 1997-12-04 |
Family
ID=24617794
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002228422A Abandoned CA2228422A1 (en) | 1996-05-29 | 1997-05-28 | Portable perfusion/oxygenation module having respiratory gas driven, mechanically linked dual pumps and mechanically actuated flow control valve for slow pulsatile cycling of oxygenated perfusate during in vitro conservation of viable transplant organs |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US5965433A (en) |
| EP (1) | EP0842261A1 (en) |
| CA (1) | CA2228422A1 (en) |
| MX (1) | MX9801137A (en) |
| WO (1) | WO1997045527A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110312423A (en) * | 2016-12-13 | 2019-10-08 | 得克萨斯州大学系统董事会 | Devices, systems, and methods for vascular tissue's perfusion |
Families Citing this family (77)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8409846B2 (en) * | 1997-09-23 | 2013-04-02 | The United States Of America As Represented By The Department Of Veteran Affairs | Compositions, methods and devices for maintaining an organ |
| AU6274899A (en) * | 1998-09-29 | 2000-04-17 | Organ Recovery Systems, Inc. | Apparatus and method for maintaining and/or restoring viability of organs |
| US6673594B1 (en) | 1998-09-29 | 2004-01-06 | Organ Recovery Systems | Apparatus and method for maintaining and/or restoring viability of organs |
| US6977140B1 (en) * | 1998-09-29 | 2005-12-20 | Organ Recovery Systems, Inc. | Method for maintaining and/or restoring viability of organs |
| US7749693B2 (en) * | 1998-09-29 | 2010-07-06 | Lifeline Scientific, Inc. | Method of determining that an organ is not suitable for transplantation and using it for testing substances |
| NL1013524C2 (en) * | 1999-11-08 | 2001-05-09 | Univ Amsterdam | Machine for organ perfusion during the transport phase of a donor organ. |
| US6497676B1 (en) | 2000-02-10 | 2002-12-24 | Baxter International | Method and apparatus for monitoring and controlling peritoneal dialysis therapy |
| US6794182B2 (en) | 2000-03-13 | 2004-09-21 | E. George Wolf, Jr. | Hyperbaric oxygen organ preservation system (HOOPS) |
| DE10015807C2 (en) * | 2000-03-24 | 2002-09-19 | Mediport Biotech Gmbh | Process and device for maintaining vital organs, extremities and tissue flaps by perfusion |
| DE10130512B4 (en) * | 2001-06-25 | 2007-08-16 | Bionethos Holding Gmbh | Device for pressure perfusion for growing and / or treating cells |
| US6677150B2 (en) * | 2001-09-14 | 2004-01-13 | Organ Transport Systems, Inc. | Organ preservation apparatus and methods |
| WO2003026419A1 (en) * | 2001-09-28 | 2003-04-03 | Hull Harry F | A simple, fully transportable device for maintaining an excised heart in optimum condition for transplantation |
| US20050069426A1 (en) * | 2002-03-26 | 2005-03-31 | Christopher Mason | Devices for use in medicine |
| AU2003215767A1 (en) * | 2002-03-26 | 2003-10-08 | University College London | Devices for use in medicine |
| US7153286B2 (en) | 2002-05-24 | 2006-12-26 | Baxter International Inc. | Automated dialysis system |
| US20030220606A1 (en) * | 2002-05-24 | 2003-11-27 | Don Busby | Compact housing for automated dialysis system |
| US6939111B2 (en) | 2002-05-24 | 2005-09-06 | Baxter International Inc. | Method and apparatus for controlling medical fluid pressure |
| US7175606B2 (en) | 2002-05-24 | 2007-02-13 | Baxter International Inc. | Disposable medical fluid unit having rigid frame |
| US7238164B2 (en) | 2002-07-19 | 2007-07-03 | Baxter International Inc. | Systems, methods and apparatuses for pumping cassette-based therapies |
| JP2005533560A (en) | 2002-07-19 | 2005-11-10 | バクスター インターナショナル インコーポレイテッド | System and method for performing peritoneal dialysis |
| US7572622B2 (en) * | 2002-08-14 | 2009-08-11 | Transmedic, Inc. | Heart preservation chamber |
| ATE363233T1 (en) * | 2002-08-23 | 2007-06-15 | Organ Recovery Systems | CONNECTION ARRANGEMENTS, PARTICULARLY FOR TRANSPLANT ORGANS |
| CA2498827A1 (en) * | 2002-09-18 | 2004-04-01 | Lifeblood Medical Inc. | Organ preservation and transportation apparatus and method |
| CA2521324C (en) * | 2003-04-04 | 2014-12-09 | Organ Recovery Systems, Inc. | Methods and apparatus for perfusion, diagnosis, storage and/or transport of an organ or tissue |
| WO2004089085A2 (en) | 2003-04-04 | 2004-10-21 | Organ Recovery Systems, Inc. | Device for separating gas from a liquid path |
| NL1024022C2 (en) * | 2003-07-30 | 2005-02-01 | Technologiestichting Stw | Portable preservation device for a donor organ. |
| EP1680155B2 (en) | 2003-10-28 | 2015-11-04 | Baxter International Inc. | Dialysis machine with improved integrity test |
| US8029454B2 (en) | 2003-11-05 | 2011-10-04 | Baxter International Inc. | High convection home hemodialysis/hemofiltration and sorbent system |
| US20050153271A1 (en) * | 2004-01-13 | 2005-07-14 | Wenrich Marshall S. | Organ preservation apparatus and methods |
| US20050214838A1 (en) * | 2004-03-10 | 2005-09-29 | Waclaw Szybalski | Methods for mapping and sequencing nucleic acids |
| US9301519B2 (en) | 2004-10-07 | 2016-04-05 | Transmedics, Inc. | Systems and methods for ex-vivo organ care |
| US9055740B2 (en) | 2004-10-07 | 2015-06-16 | Transmedics, Inc. | Systems and methods for ex-vivo organ care |
| US8304181B2 (en) | 2004-10-07 | 2012-11-06 | Transmedics, Inc. | Method for ex-vivo organ care and for using lactate as an indication of donor organ status |
| US7287504B2 (en) * | 2004-10-29 | 2007-10-30 | Siemens Vdo Automotive Canada Inc. | Over-center actuator |
| WO2006118990A2 (en) * | 2005-04-29 | 2006-11-09 | Transplan, Inc. | Method and device for organ perfusion |
| US9078428B2 (en) | 2005-06-28 | 2015-07-14 | Transmedics, Inc. | Systems, methods, compositions and solutions for perfusing an organ |
| CA2649703C (en) | 2006-04-19 | 2019-01-08 | Transmedics, Inc. | Systems and methods for ex vivo organ care |
| US20080145919A1 (en) * | 2006-12-18 | 2008-06-19 | Franklin Thomas D | Portable organ and tissue preservation apparatus, kit and methods |
| US9457179B2 (en) | 2007-03-20 | 2016-10-04 | Transmedics, Inc. | Systems for monitoring and applying electrical currents in an organ perfusion system |
| US9247728B2 (en) * | 2008-01-31 | 2016-02-02 | Transmedics, Inc. | Systems and methods for ex vivo lung care |
| EP2278874B1 (en) * | 2008-04-22 | 2019-03-20 | The Board of Regents of The University of Texas System | Fluidics-based pulsatile perfusion organ preservation device |
| US9514283B2 (en) | 2008-07-09 | 2016-12-06 | Baxter International Inc. | Dialysis system having inventory management including online dextrose mixing |
| US8062513B2 (en) | 2008-07-09 | 2011-11-22 | Baxter International Inc. | Dialysis system and machine having therapy prescription recall |
| US10091985B2 (en) * | 2009-06-18 | 2018-10-09 | Giner, Inc. | Perfusing an organ with an in situ generated gas |
| US9357764B2 (en) | 2009-06-18 | 2016-06-07 | Giner, Inc. | System for fluid perfusion of biological matter comprising tissue |
| US9320269B2 (en) | 2009-09-25 | 2016-04-26 | John Brassil | Organ preservation system |
| DE102010004600A1 (en) | 2010-01-13 | 2011-07-14 | Marseille, Oliver, Dr.-Ing., 52066 | Arrangement with a blood pump and a gas exchanger for extracorporeal membrane oxygenation |
| KR101866587B1 (en) * | 2010-06-24 | 2018-06-11 | 그라코 미네소타 인크. | Dual pump fluid proportioner with adjustable motor position |
| CN103002991B (en) * | 2010-06-24 | 2016-01-20 | 格瑞克明尼苏达有限公司 | For the fluid valve assembly of fluid proportional adjuster |
| AU2011295629B2 (en) | 2010-09-01 | 2014-05-01 | Organ Transport Pty Ltd | Perfusion composition |
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| US9426979B2 (en) | 2011-03-15 | 2016-08-30 | Paragonix Technologies, Inc. | Apparatus for oxygenation and perfusion of tissue for organ preservation |
| US9253976B2 (en) | 2011-03-15 | 2016-02-09 | Paragonix Technologies, Inc. | Methods and devices for preserving tissues |
| US8828710B2 (en) | 2011-03-15 | 2014-09-09 | Paragonix Technologies, Inc. | System for hypothermic transport of samples |
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| CA3022104C (en) | 2011-04-14 | 2024-04-09 | Transmedics, Inc. | Organ care solution for ex-vivo machine perfusion of donor lungs |
| US9642625B2 (en) | 2011-04-29 | 2017-05-09 | Lifeline Scientific, Inc. | Cannula for a donor organ with or without an aortic cuff or patch |
| US8828034B2 (en) | 2011-04-29 | 2014-09-09 | Lifeline Scientific, Inc. | Cannula |
| US9022978B2 (en) | 2011-04-29 | 2015-05-05 | Lifeline Scientific, Inc. | Universal sealring cannula |
| WO2013029044A1 (en) * | 2011-08-25 | 2013-02-28 | Breonics, Inc. | Organ chamber for ex vivo warm perfusion |
| US9560846B2 (en) | 2012-08-10 | 2017-02-07 | Paragonix Technologies, Inc. | System for hypothermic transport of biological samples |
| US8785116B2 (en) * | 2012-08-10 | 2014-07-22 | Paragonix Technologies, Inc. | Methods for evaluating the suitability of an organ for transplant |
| CN110101485B (en) | 2013-09-24 | 2021-07-06 | 吉纳生命科学公司 | System for gas treatment of cell implants |
| CN113287600B (en) | 2014-06-02 | 2022-08-19 | 特兰斯迈迪茨公司 | Perfusion circuit and system for perfusion of isolated liver and system for preservation thereof |
| USD765874S1 (en) | 2014-10-10 | 2016-09-06 | Paragonix Technologies, Inc. | Transporter for a tissue transport system |
| WO2016090498A1 (en) | 2014-12-12 | 2016-06-16 | Freed Darren | Apparatus and method for organ perfusion |
| IL298619B1 (en) | 2015-09-09 | 2024-02-01 | Transmedics Inc | Aortic cannula for ex vivo organ care system |
| RU2617093C1 (en) * | 2016-03-16 | 2017-04-19 | Общество С Ограниченной Ответственностью "Биософт-М" | Perfusion circuit pump drive unit for restoration of blood circulation and oxygenation |
| WO2018093956A1 (en) | 2016-11-15 | 2018-05-24 | Giner, Inc. | Percutaneous gas diffusion device suitable for use with a subcutaneous implant |
| JP7044268B2 (en) | 2016-11-15 | 2022-03-30 | ガイナー ライフ サイエンシズ，インク． | Self-regulating electrolytic gas generator and implant system with it |
| WO2018226993A1 (en) | 2017-06-07 | 2018-12-13 | Paragonix Technologies, Inc. | Apparatus for tissue transport and preservation |
| US11179516B2 (en) | 2017-06-22 | 2021-11-23 | Baxter International Inc. | Systems and methods for incorporating patient pressure into medical fluid delivery |
| WO2019222704A1 (en) | 2018-05-17 | 2019-11-21 | Giner Life Sciences, Inc. | Electrolytic gas generator with combined lead and gas port terminals |
| RU185905U1 (en) * | 2018-06-29 | 2018-12-21 | Акционерное общество "Научно-производственное объединение "СПЛАВ" | Automated device for emergency restoration of blood circulation |
| DE102019135506A1 (en) * | 2019-12-20 | 2021-06-24 | Corlife Ohg | Containers, sealing lids and vessels for transplant objects and methods and systems for providing three-dimensional structural data and for sterilizing a transplant object |
| US11632951B2 (en) | 2020-01-31 | 2023-04-25 | Paragonix Technologies, Inc. | Apparatus for tissue transport and preservation |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3406531A (en) * | 1964-08-25 | 1968-10-22 | Emil S. Swenson | Apparatus for maintaining organs in a completely viable state |
| US3632473A (en) * | 1969-04-21 | 1972-01-04 | Univ California | Method and apparatus for preserving human organs extracorporeally |
| US3892628A (en) * | 1969-10-06 | 1975-07-01 | Baxter Laboratories Inc | Preservation of organs |
| US3639084A (en) * | 1970-04-06 | 1972-02-01 | Baxter Laboratories Inc | Mechanism for control pulsatile fluid flow |
| US3935065A (en) * | 1971-09-02 | 1976-01-27 | Roland Karl Doerig | Procedure for conservation of living organs and apparatus for the execution of this procedure |
| DE2241698C2 (en) * | 1971-09-02 | 1982-08-26 | Roland Dr.med. Zürich Doerig | Process for organ preservation and device for carrying out this process |
| US3881990A (en) * | 1971-11-24 | 1975-05-06 | Waters Instr Inc | Method of transporting and storing organs while retaining the organs in a viable condition |
| US3877843A (en) * | 1973-05-21 | 1975-04-15 | Baxter Laboratories Inc | Pulsatile pumping system |
| US5051352A (en) * | 1987-10-07 | 1991-09-24 | The Regents Of The University Of California | Apparatus and method of preserving the viability of animal organs |
| US5326706A (en) * | 1989-07-17 | 1994-07-05 | Research Foundation Of State University Of New York | Homeostatic organ preservation system |
| FR2667297B1 (en) * | 1990-09-28 | 1994-05-27 | Electrolux Sarl | AIR-CONDITIONED MEDICAL CONTAINER. |
| US5338662A (en) * | 1992-09-21 | 1994-08-16 | Bio-Preserve Medical Corporation | Organ perfusion device |
| US5356771A (en) * | 1993-03-11 | 1994-10-18 | Board Of Regents, The University Of Texas System | Combined perfusion and oxygenation organ preservation apparatus |
| US5362622A (en) * | 1993-03-11 | 1994-11-08 | Board Of Regents, The University Of Texas System | Combined perfusion and oxygenation apparatus |
-
1996
- 1996-05-29 US US08/652,696 patent/US5965433A/en not_active Expired - Fee Related
-
1997
- 1997-05-28 EP EP97925738A patent/EP0842261A1/en not_active Withdrawn
- 1997-05-28 WO PCT/US1997/009000 patent/WO1997045527A1/en not_active Application Discontinuation
- 1997-05-28 CA CA002228422A patent/CA2228422A1/en not_active Abandoned
-
1998
- 1998-02-10 MX MX9801137A patent/MX9801137A/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110312423A (en) * | 2016-12-13 | 2019-10-08 | 得克萨斯州大学系统董事会 | Devices, systems, and methods for vascular tissue's perfusion |
Also Published As
| Publication number | Publication date |
|---|---|
| MX9801137A (en) | 1998-11-29 |
| US5965433A (en) | 1999-10-12 |
| EP0842261A1 (en) | 1998-05-20 |
| WO1997045527A1 (en) | 1997-12-04 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |