Patent Publication Number: US-2022211031-A1

Title: Method and system for ex-vivo heart perfusion

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. application Ser. No. 16/606,404, filed Oct. 18, 2019, which is a U.S. national stage application under 35 U.S.C. § 371 of International Application No. PCT/CA2018/000068, filed Apr. 5, 2018, which claims the benefit of U.S. Provisional Patent Application No. 62/488,123, filed Apr. 21, 2017, the entire contents of each priority application of which is incorporated herein by reference. 
    
    
     FIELD 
     This relates to preservation and evaluation of isolated hearts, and in particular to performance of perfusion on hearts in multiple modes of operation. 
     BACKGROUND 
     Cardiac transplantation is an important treatment option for many patients with advanced heart failure. Its widespread application however, is limited by a scarcity of usable donor hearts as compared to eligible recipients. Cold static storage, the accepted technique for organ preservation between heart excision and transplantation, does not provide a means for differentiating between grafts with reversible damage and those with irreversible damage. By providing a platform for reanimating and assessing donor heart viability, Ex-Vivo Heart Perfusion (EVHP) systems have been developed to address the paucity of donor organs. 
     One common mode for EVHP, Langendorff mode, involves re-animating isolated hearts by providing oxygenated perfusate to the aorta in a retrograde direction. While well established, Langendorff Mode perfusion is a non-working mode, precluding the assessment of physiologically relevant contractile function. 
     Some existing EVHP systems may allow for the functional assessment of the left side of the heart by facilitating a so-called working mode. Right ventricular functional parameters however, which might be important predictors for post-transplant organ outcomes, have remained unexplored. A system capable of facilitating both preservation and biventricular cardiac assessment would be advantageous. 
     SUMMARY 
     According to one aspect of the invention, there is provided a system for performing perfusion on a heart having a left atrium, a right atrium, a pulmonary artery, and an aorta, the system comprising: a reservoir containing fluid; a first pump configured to deliver a first portion of the fluid to a left-side line; a left atrial line connected to the left-side line via a left atrial line clamp, the left atrial line configured to connect to the left atrium; an aortic line connected to the left-side line via an aortic line clamp, the aortic line configured to connect to the aorta of the heart; a reservoir return line connected at a distal end to the reservoir, the reservoir return line further connected at a proximal end to the aortic line via reservoir return clamp; and a pulmonary return line connected at a distal end to the reservoir, the pulmonary return line configured to connect at a proximal end to the pulmonary artery. 
     In some embodiments, a second pump is connected to the reservoir, the second pump configured to pump a second portion of the fluid to a right-side line, and the right-side line is configured to connect to the right atrium. 
     In some embodiments, the left atrial line comprises an adjustable resistor. 
     In some embodiments, the system further comprises a return bypass line connected in parallel with the reservoir return line via a bypass clamp. 
     In some embodiments, the return bypass line includes a first afterload configured to store and release energy. 
     In some embodiments, the pulmonary return line comprises a second afterload configured to store and release energy. 
     In some embodiments, the left-side line comprises a first valve configured to prevent the flow of gas bubbles. 
     In some embodiments, the reservoir return line includes a second valve configured to prevent the flow of air from the reservoir to the aortic line. 
     In some embodiments, the system further comprises a sampling port connected to the left-side line via a third valve, the sampling port configured to facilitate extraction of samples of the fluid. 
     In some embodiments, at least one of the first pump and the second pump is a centrifugal pump. 
     In some embodiments, the second pump is configured to pump the second portion of the fluid to the right atrium with a specified pressure. 
     In some embodiments, the aortic line clamp is set to an open position, the left atrial line clamp is set to an open position, and the reservoir return clamp is set to an open position. 
     In some embodiments, the aortic line clamp is set to an open position, the left atrial line clamp is set to an open position, and the reservoir return clamp is set to an open position. 
     In some embodiments, the system further comprises a return bypass line connected in parallel with the reservoir return line via a bypass clamp, the aortic line clamp is set to a closed position, the left atrial line clamp is set to an open position, the reservoir return clamp is set to a closed position, and the bypass clamp is set to an open position. 
     In some embodiments, the aortic line clamp is set to an open position, the left atrial line clamp is set to a closed position, and the reservoir return clamp is set to a closed position. 
     In some embodiments, the aortic line clamp is set to a closed position, the left atrial line clamp is set to an open position, the reservoir return clamp is set to a closed position, and the bypass clamp is set to an open position. 
     In some embodiments, the aortic line clamp is set to an open position, the left atrial line clamp is set to a closed position, and the reservoir return clamp is set to a closed position. 
     According to another aspect, there is provided a method of performing perfusion on a heart having a left atrium, a right atrium, a pulmonary artery, and an aorta, the method comprising: providing a reservoir containing fluid; providing a first pump configured to deliver a first portion of the fluid to a left-side line; providing a left atrial line connected to the left-side line via a left atrial line clamp, wherein the left atrial line is configured to connect to the left atrium; providing an aortic line connected to the left side line via an aortic line clamp, the aortic line configured to connect to the aorta; providing a reservoir return line connected at a proximal end to the aortic line via a reservoir return clamp, the reservoir return line further connected at a distal end to the reservoir; and providing a pulmonary return line connected at a distal end to the reservoir, the pulmonary return line configured to connect at a proximal end to the pulmonary artery. 
     In some embodiments, the method further comprises: providing a right side line configured to connect to the right atrium; and providing a second pump connected to the reservoir, the second pump configured to pump a second portion of the fluid to the right-side line. 
     In some embodiments, the aortic line clamp is set to an open position, the left atrial line clamp is set to a closed position, and the reservoir return clamp is set to a closed position, and the method further comprises: delivering the first portion of the fluid to the aorta via the aortic line; circulating the first portion of the fluid through coronary arteries, heart tissues, and coronary veins of the heart; and returning an output fluid from the pulmonary artery to the reservoir via the pulmonary return line. 
     In some embodiments, the pulmonary return line includes a second afterload configured to store and release energy. 
     In some embodiments, the aortic line clamp is set to an open position, the left atrial line clamp is set to an open position, and the reservoir return clamp is set to an open position. 
     In some embodiments, the method further comprises: delivering at least some of the first portion of the fluid to the aorta via the aortic line; and delivering at least some of the first portion of the fluid to the left atrium via the left atrial line. 
     In some embodiments, the method further comprises: during a first period of time, circulating the at least some of the first portion of the fluid through one or more of coronary arties, heart tissue, and coronary veins of the heart; and during a second period of time, delivering at least some of the first portion of the fluid to the reservoir via the reservoir return line. 
     In some embodiments, the method further comprises: controlling a pressure at the left atrium by adjusting a variable resistor in the left atrial line. 
     In some embodiments, the method further comprises providing a right side line configured to connect to the right atrium; and providing a second pump connected to the reservoir, configured to pump a second portion of the fluid to the right atrium. 
     In some embodiments, the method further comprises: providing a bypass line connected in parallel with the reservoir return line via a bypass clamp, the aortic line clamp is set to a closed position, the left atrial line clamp is set to an open position, the reservoir return clamp is set to a closed position, and the bypass clamp is set to an open position. 
     In some embodiments, the method further comprises: delivering the first portion of the fluid to the left atrium via the left atrial line; and returning an output fluid from the aorta to the reservoir via the aortic line, the reservoir return line, and the bypass line. 
     In some embodiments, returning the output fluid from the aorta to the reservoir comprises the output fluid travelling through a first afterload in the bypass line, and the first afterload is configured to store and release energy. 
     In some embodiments, returning an output fluid from the aorta to the reservoir comprises the output fluid travelling through a valve configured to prevent backflow from the reservoir. 
     In some embodiments, the method further comprises: providing a right side line configured to connect to the right atrium; and providing a second pump connected to the reservoir, the second pump configured to pump a second portion of the fluid to the right atrium. 
     In some embodiments, the method further comprises: providing a right side line configured to connect to the right atrium; and providing a second pump connected to the reservoir, the second pump configured to pump a second portion of the fluid to the right atrium. 
    
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
       In the figures, which depict example embodiments: 
         FIG. 1A  is a block diagram of an example system for performing perfusion on a heart; 
         FIG. 1B  is a block diagram of an alternative embodiment of an example system for performing perfusion; 
         FIG. 2A  is a block diagram of the example system of  FIG. 1A  configured to operate in Langendorff mode; 
         FIG. 2B  is a block diagram of the example system of  FIG. 1B  configured to operate in Langendorff mode; 
         FIG. 2C  is a simplified block diagram of the example systems of  FIGS. 2A and 2B  in operation; 
         FIG. 3A  is a block diagram of the example system of  FIG. 1A  configured to operate in a pump-supported working mode; 
         FIG. 3B  is a simplified block diagram of the example system of  FIG. 3A  in operation; 
         FIG. 3C  is a block diagram of the example system of  FIG. 1B  configured to operate in a pump-supported working mode; 
         FIG. 3D  is a simplified block diagram of the example system of  FIG. 3C  in operation; 
         FIG. 4A  is a block diagram of the example system of  FIG. 1A  configured to operate in a passive working mode; 
         FIG. 4B  is a simplified block diagram of the example system of  FIG. 4A  in operation; 
         FIG. 4C  is a block diagram of the example system of  FIG. 1B  configured to operate in a passive working mode; 
         FIG. 4D  is a simplified block diagram of the example system of  FIG. 4C  in operation; 
         FIG. 5A  is a block diagram of the example system of  FIG. 1A  configured to operate in a right-sided working mode; 
         FIG. 5B  is a block diagram of the example system of  FIG. 1B  configured to operate in a right-sided working mode; 
         FIG. 5C  is a simplified block diagram of the example systems of  FIGS. 5A and 5B  in operation; 
         FIG. 6  is a flow chart for an example method of performing a perfusion on a heart, according to some embodiments. 
     
    
    
     DETAILED DESCRIPTION 
     Some strategies for ex vivo perfusion focus on different Working Modes enabling graft evaluation during perfusion. According to a first strategy, a two-chamber Working Mode can be employed in which blood is provided only to the left atrium and ejected from the left ventricle to perfuse the coronaries. According to another strategy, a four-chamber working heart platform using a pump to load the left atrium and a reservoir to load the right atrium by gravity can be employed. Decoupled designs of the loading system, however, may make it difficult to individually manipulate the preload of the left and right sides. Additionally, such systems may rely on the use of reservoir height to control right atrial pressure, which can limit the system&#39;s ability to facilitate precise control of atrial loading throughout the perfusion period. 
       FIG. 1A  is a block diagram of an example system  100  for performing a perfusion on a heart  200 . In some embodiments, the heart  200  is an animal heart. In some embodiments, the heart  200  is a human heart. As depicted, heart  200  further includes coronary arteries  225 , heart tissue  230 , and coronary veins  235 . In  FIG. 1A , RA denotes the right atrium, LA denotes the left atrium, RV denotes the right ventricle, LV denotes the left ventricle, PA denotes the pulmonary artery, and A denotes the aorta of heart  200 . 
     As depicted, example system  100  comprises a reservoir  110 , an oxygenator  120 , a first pump  131 , a second pump  132 , a reservoir clamp  141 , an aortic line clamp  142 , a left atrial line clamp  143 , a bypass clamp  144 , a reservoir return clamp  145 , a priming clamp  146 , afterloads  151 ,  152 , variable resistor  160 , filter  170 , sampling port  115 , and a plurality of valves  191 - 193 . System  100  further comprises a plurality of lines  181 - 189  operable to transport fluids. The system  100  is operable to connect to one or more locations  205 ,  210 ,  215 ,  220  on heart  200 . As depicted, clamps  141 - 146  are illustrated using a clamp symbol. Throughout the specification and drawings, when the clamps are illustrated as being parallel to a line, this signifies that the clamp is in an open position. When the clamps are illustrated as being perpendicular to a line, this signifies that the clamp is in position. In  FIG. 1A , each of clamps  141 - 146  are illustrated in the “open” position. 
     It should be appreciated that the example embodiment of system  100  depicted in  FIG. 1A  is an example and that various embodiments need not include every single element depicted in  FIG. 1A . Further example configurations of system  100  may include some or all of the components outlined above in relation to  FIG. 1A . 
     Reservoir  110  is used as a container for fluids. Fluids used for perfusion are referred to herein after as perfusate. Perfusate may include, for example, blood, and/or other movable materials used for perfusion. In some embodiments, the perfusate in reservoir  110  is de-oxygenated. Reservoir  110  is connected to first pump  131 . In some embodiments, first pump  131  is located at a lower vertical height than reservoir  110 , thereby allowing gravity to assist with the flow of perfusate from reservoir  110  to first pump  131 . In some embodiments, the first pump  131  can apply a suction pressure to reservoir  110  to assist with drawing perfusate out from reservoir  110 . In some embodiments, the first pump  131  is a centrifugal pump. 
     In some embodiments, a second pump  132  is connected downstream from reservoir  110 , via reservoir clamp  141 . Reservoir clamp  141  can be switched between an open state (allowing perfusate to flow to second pump  132 ) and a closed state (preventing the flow of perfusate from reservoir  110  to second pump  132 ). In some embodiments, one or both of first and second pumps  131 ,  132  are centrifugal pumps. In some embodiments, the output of second pump  132  is connected via right-side line  189  to connection point  205  of heart  200 . In some embodiments, connection point  205  of heart  200  corresponds to the right atrium of heart  200 . 
     As depicted, perfusate flows from first pump  131  to oxygenator  120 . In some embodiments, oxygenator  120  further comprises a heat exchanger. In some embodiments, an output of oxygenator  120  is connected to reservoir  110  by way of purge line  181 . Purge line  181  is operable to allow gas to vent from oxygenator  120  and back into reservoir  110 . 
     In some embodiments, an output line from oxygenator  120  is further connected to a filter  170 . Filter  170  may be used to filter various materials from the fluid. Filter  170  may be an arterial filter, which may be used to filter white blood cells (e.g. leukocytes) from the perfusate. Filter  170  may also serve as a de-airing device or bubble trap. In some embodiments, a one-way valve  191  is connected downstream from filter  170 . Valve  191  may be useful in preventing the flow of any air bubbles into left-side line  182 . In some embodiments, the perfusate flowing through line  182  may ultimately flow to one or more portions on the left side of heart  200 . The introduction of air bubbles to heart  200  may cause an air embolism in the coronary arteries  225 , which may cause fibrillation. This may cause damage to heart  200  or even loss of heart  200 . Thus, it is desirable to prevent the flow of air bubbles in left-side line  182  through the use of valve  191 . 
     From valve  191 , left-side line  182  proceeds until separating into left atrial line  183  and aortic line  184 . In some embodiments, left-side line  182  and left atrial line  183  are separated by left atrial line clamp  143 . In some embodiments, left-side line  182  and aortic line  184  are separated by aortic line clamp  142 . In some embodiments, left atrial line  183  is connected to variable resistor  160 . After variable resistor  160 , left atrial line  183  is then operable to be connected to connection  210  of heart  200 . In some embodiments, connection  210  corresponds to the left atrium of heart  200 . 
     In some embodiments, aortic line  184  is connected to connection  220  of heart  200 . In some embodiments, connection  220  corresponds to the aorta of heart  200 . In some embodiments, aortic line  184  is further connected to pulmonary return line  188  via priming clamp  146 . Priming clamp  146  can be switched from an open state (connecting aortic line  184  to pulmonary return line  188 ) and a closed state (disconnecting aortic line  184  and pulmonary return line  188 ). Pulmonary return line  188  is connected to a connection  215  of heart  200 . In some embodiments, connection  215  corresponds to the pulmonary artery of heart  200 . 
     As depicted in  FIG. 1A , pulmonary return line  188  is further connected to and drains into reservoir  110  via reservoir return line  186 . In some embodiments, a bypass line  185  is connected in parallel with reservoir return line  186  via bypass clamp  144 . In some embodiments, bypass line  185  includes an afterload  151  configured to store and release energy. In some embodiments, reservoir return line  186  includes a one-way valve  192 . One-way valve is operable to prevent backflow of air bubbles from reservoir  110  into reservoir return line  186 . This may prevent air bubbles from reservoir  110  from reaching heart  200  and potentially causing damage. It should be noted that although  FIG. 1A  includes both reservoir return line  186  and bypass line  185 , in some embodiments, bypass line  185  may be omitted. 
     In some embodiments, reservoir return line  186  connects to aortic line  184 . In some embodiments, reservoir return clamp  145  enables flow from aortic line  184  to reservoir  110 . Reservoir return clamp  145  may be changed from an open state (in which perfusate flows from aortic line  184  to reservoir  110 , optionally via one-way valve  192 ). Bypass clamp  144  may be changed from an open state (in which perfusate flows via bypass line  185  via afterload  151  to reservoir return line  186  and ultimately to reservoir  110 , optionally via one-way valve  192 ). In some embodiments, clamps  144  and  145  are not in an open state simultaneously during operation. In some embodiments, both of clamps  144  and  145  may be closed. Optionally, an additional clamp (not shown) can be included between aortic line  184  and the point at which bypass line  185  branches from reservoir return line  186 , which may minimize the amount of perfusate that exits aortic line  184  when both of clamps  144  and  145  are closed. 
     An alternative embodiment for system  100  is shown in  FIG. 1B . As depicted in  FIG. 1B , pulmonary return line  188  is further connected to and drains into reservoir  110  via first return line  1850  or second return line  1860 . In some embodiments, first return line  1850  includes afterload  152 . In some embodiments, first return line  1850  and second return line  1860  join at a junction to form reservoir return line  187 . In some embodiments, reservoir return line  187  includes one-way valve  192 . During low flow conditions, there may be a tendency for air from reservoir  110  to flow to heart  200 . As noted above, it is preferable not to allow air bubbles to travel to heart  200 . One-way valve  192  prevents backflow of air from reservoir  110  and thus reduces the likelihood of air from reservoir  110  travelling to heart  200 . It should be noted that although  FIG. 1B  includes both first return line  1850  and second return line  1860 , in some embodiments one of lines  1850  and  1860  is sufficient. In some embodiments, neither of lines  1850  and  1860  is present. 
     In some embodiments (e.g.  FIG. 1B ), first return line  1850  connects aortic line  184  to an afterload  151  via first return clamp  148 . First return clamp  148  can be switched between an open state (connecting first return line  1850  to afterload  151 ) and a closed state (preventing first return line  1850  from being in fluid communication with afterload  151 ). Afterload  151  then connects via first return line  1850  to reservoir return line  187 , which connects to reservoir  110 . In some embodiments, a one-way valve  192  separates reservoir return line  187  and reservoir  110 . 
     In some embodiments (e.g.  FIG. 1B ), second return line  1860  connects to reservoir return line  187 . Reservoir return line  187  then connects to reservoir  110 . In some embodiments, second return line  1860  connects to reservoir return line  187  via second return clamp  149 . Second return clamp  149  can be switched between an open state (connecting second return line  1860  to reservoir return line  187 ) and a closed state (preventing second return line  1860  from being in fluid communication with reservoir return line  187 ). 
     Some embodiments include afterloads  151 ,  152 . Afterloads  151 ,  152  are elements which are operable to store energy (e.g. in the form of elastic potential energy) and subsequently release that stored energy. The stored energy may be exerted in the opposite direction in certain situations. An afterload element may include, for example, a balloon, a Windkessel, a membrane partially filled with gas, a spring-loaded piston, or a compliant membrane operable to store energy. In some embodiments, an afterload element simulates the behaviour of blood vessels (which are known to expand in high pressure conditions and return to their resting size (or contract passively) when pressure is reduced). 
     As perfusate flows into an afterload element  151 ,  152 , energy is gradually stored (e.g. as a balloon fills, energy is stored in the form of elastic potential energy as the balloon stretches). Likewise, fluid can exert a pressure against a spring-loaded piston, causing the spring to store elastic potential energy. Afterload elements  151 ,  152  may be useful in simulating the pressure caused by the circulatory system external to heart  200 . For example, during regular functioning operation of a circulatory system, blood vessels may stretch when subjected to increased pressure (e.g. during systole, when heart muscles contract and blood is forced into blood vessels). When that increased pressure subsides (e.g. during diastole, when heart muscles relax and chambers fill with blood), the blood vessels may then return to their resting size (or contract passively). 
     Oxygenator  120  exposes fluids to oxygen. For example, oxygenator  120  may accept deoxygenated perfusate as an input, and output oxygenated perfusate. In some embodiments, an output of oxygenator  120  may be further connected to sampling port  115  via a one-way valve  193 . Sampling port  115  is then connected to reservoir  110 . Sampling port  115  may be used to extract samples of blood or perfusate for analysis. Samples may be taken to analyze, for example, levels of pH, lactate, hemoglobin, hematocrit, oxygen saturation, electrolytes, lactate, blood gases, other metabolites (e.g. liver enzymes, creatinine, urea, glucose), as well as the partial pressure of oxygen, and the like. Sampled perfusate can also be stored and used for assays at later times (e.g. for the quantification of endothelin-1, troponin 1, oxidative stress markers, or the like). 
     In some embodiments, system  100  is operable to switch between a plurality of different operating modes.  FIG. 2A  is a block diagram of the example system of  FIG. 1A  configured to operate in Langendorff mode.  FIG. 2B  is a block diagram of the example system of  FIG. 1B  configured to operate in Langendorff mode. Langendorff mode may be used to reanimate and/or resuscitate a candidate heart from a state of cardiac arrest, asystole or cold storage, to defibrillate a heart undergoing fibrillation, and may also be used to test the performance of various mechanical and electrophysiological parameters associated with a candidate heart  200 . 
     As depicted in  FIGS. 2A and 2B , reservoir clamp  141  is in a closed position (denoted by clamp  141  being perpendicular to the line leading to second pump  132 ), and the second pump  132  is turned off. Hereinafter, the illustration of a clamp being perpendicular to a line in the figures denotes that the clamp is closed. Thus, no perfusate is sent to input  205  of heart  200  via line  189 . Left atrial clamp  143  is in a closed position, and perfusate carried in left-side line  182  does not flow to left atrial line  183  or to variable resistor  160 . Aortic line clamp  142  is in an open position, which allows perfusate to pass from left-side line  182  to aortic line  184  and to input  220  of heart  200 . 
     In  FIG. 2A , bypass clamp  144  and reservoir return clamp  145  are both closed, thereby preventing any flow from aortic line  184  to reservoir  110 . In  FIG. 2B , first return clamp  148  and second return clamp  149  are in closed positions, thereby preventing fluid flow through any of lines  1850 ,  1860  and  187 , as well as afterload  151 . Priming clamp  146  is in a closed position, and therefore aortic line  184  and pulmonary return line  188  are not in fluid communication. 
       FIG. 2B  is a simplified block diagram of the example system of  FIGS. 2A and 2B  in operation, in which lines which are not operable to carry fluids are not shown. In operation, perfusate from reservoir  110  flows to the first pump  131 . In some embodiments, the first pump  131  is located at a lower height than reservoir  110 , and fluid flow to pump  131  is aided by gravity. In some embodiments, the first pump  131  is a centrifugal pump. In some embodiments, first pump  131  is set to approximately 1500 rpm, although any suitable speed can be chosen. Perfusate then flows from first pump  131  to oxygenator  120 , which exposes the perfusate to oxygen. In some embodiments, oxygenator  120  further comprises a heat exchanger. Excess gas may be returned to reservoir  110  via purge line  181 . In some embodiments, some of the oxygenated perfusate output from oxygenator  120  passes through one-way valve  193  and to sampling port  115 , and then back to reservoir  110 . In some embodiments, the above-described line with one-way valve  193  and sampling port  115  is not present. 
     Oxygenated perfusate flows from the oxygenator  120  to filter  170 , and then through one-way valve  191 . In some embodiments, one-way valve  191  is operable to prevent gas bubbles from flowing through left-side line  182 . Gas bubbles may cause damage to heart  200  if allowed to travel to heart  200 , as noted above. 
     The oxygenated, filtered perfusate then flows (under pressure from first pump  131 ) through left-side line  182  and through to aortic line  184 . The oxygenated, filtered perfusate ultimately flows to connection  220  of heart  200 . In some embodiments, the connection  220  corresponds to the aorta of heart  200 . Because the aortic valve is a one-way valve, entry into the left ventricle of heart  200  is prevented, and the perfusate is diverted. 
     The oxygenated, filtered perfusate applies a pressure to the aortic valve of heart  200 . In some embodiments, the pressure is approximately 50 mmHg at the aortic valve. This pressure may cause the aortic valve to close, and since the perfusate cannot enter the left ventricle, the perfusate is instead forced to pass through the coronary arteries  225 . As the perfusate passes through various heart tissues (e.g. muscle and other cells—depicted as heart tissue  230 ), oxygen in the perfusate is consumed. The deoxygenated perfusate then flows through coronary veins  235  and empties into the right atrium of heart  200 . The deoxygenated perfusate then flows from the right atrium to the right ventricle, and flows out of the pulmonary artery at connection  215  and into pulmonary return line  188 . The deoxygenated perfusate is then passed through afterload  152  and ultimately to reservoir  110 . 
     As will be appreciated, the pressure generated by first pump  131  is sufficient to cause the perfusate to flow through oxygenator  120 , filter  170 , valve  191 , left-side line  182 , aortic line  184 , coronary arteries  225 , heart tissue  230  and coronary veins  235 . In some embodiments, once the perfusate enters the right atrium, the pumping mechanism of heart  200  causes the perfusate to move to the right ventricle, and ultimately out to the pulmonary artery and into pulmonary return line  188 . In some embodiments, it is desirable to prevent a condition in which there is negative pressure in the pulmonary artery. As noted above, the afterload  152  is operable to store elastic potential energy as fluid flows through afterload  152 , and during moments of reduced pressure (e.g. diastole), the afterload  152  applies a reverse pressure, which may prevent a condition of negative pressure in the pulmonary artery. 
     The Langendorff mode may be useful for measuring certain properties of a candidate heart  200 , including, but not limited to myocardial oxygen consumption, lactate extraction, metabolite production, or the like. The perfusate can be sampled at sampling port  115  and analyzed for any number of parameters described herein. Generally, the Langendorff mode will be the first mode that a candidate heart will be subjected to during ex-vivo (i.e. outside of the body) testing. 
     In some embodiments, system  100  is further operable to operate in a pump-supported working mode.  FIG. 3A  is a block diagram of the example system of  FIG. 1A  configured to operate in a pump-supported working mode.  FIG. 3C  is a block diagram of the example system of  FIG. 1B  configured to operate in a pump-supported working mode. 
     As depicted in  FIG. 3A , in pump-supported working mode, aortic line clamp  142  is open, left atrial clamp  143  is open, bypass clamp  144  is closed, reservoir return clamp  145  is open, and priming clamp  146  is closed. As depicted in  FIG. 3C , in pump-supported working mode, aortic line clamp  142  is open, left atrial clamp  143  is open, first return clamp  148  is closed, second return clamp  149  is open, and priming clamp  146  is closed. Optionally, reservoir clamp  141  may be set to an open state and second pump  132  may be activated.  FIGS. 3A, 3B, 3C and 3D  depict example embodiments in which the reservoir clamp  141  is open, although embodiments are contemplated in which reservoir clamp  141  is closed while in pump supported working mode.  FIGS. 3B and 3D  are simplified block diagrams of the example systems of  FIGS. 3A and 3C  in operation, respectively, in which the reservoir clamp  141  is open and second pump  132  is activated. 
     During operation in pump-supported working mode, perfusate flows from reservoir  110  to first pump  131 . The perfusate is then pumped to oxygenator  120 , filter  170 , and valve  191  to left-side line  182 . The perfusate then flows from left-side line  182  to both left atrial line  183  and aortic line  184 . A first portion of perfusate flows into left atrial line  183 , and a second portion of perfusate flows into aortic line  184 . The first portion of fluid in left atrial line  183  flows to connection  210  of heart  200  via variable resistor  160 . In some embodiments, connection  210  corresponds to the left atrium of heart  200 . The second portion of fluid in aortic line  184  flows into connection  220  of heart  200 . In some embodiments, connection  220  corresponds to the aorta of heart  200 . 
     The relative flow of fluid between left atrial line  183  and aortic line  184  may be controlled by adjusting the resistance of variable resistor  160 . In some embodiments, variable resistor  160  can be any of an adjustable tubing clamp, a cluster of small tubes (which increase the friction experienced by the perfusate over a similar cross-sectional area), or a system of bends in the tubing. In some embodiments, the variable resistor  160  is adjusted such that the left atrial pressure is between approximately 5 to 10 mmHg. The diastolic pressure (i.e. the pressure in the aorta during diastole) may be maintained around 30 mmHg in pump-supported working mode. In some embodiments, the first pump  131  is a centrifugal pump. In some embodiments, the first pump has a rotational speed of approximately 2000 rpm in pump-supported working mode. It will be appreciated by a person skilled in the art that the rotational speed of the first pump  131  can be adjusted in order to achieve a desired operating condition. 
     During diastole (denoted by the arrows with the letter D in  FIGS. 3B and 3D ), the perfusate flowing through aortic line  184  flows to connection  220  of heart  200  (which may correspond to the aorta). The aortic valve of heart  200  will not allow fluid to flow into the left ventricle, and so the perfusate flows through coronary arteries  225 , heart tissue  230 , and coronary veins  235 , and then into the right atrium of heart  200 . The perfusate then flows out of the right ventricle via the pulmonary artery, and then through pulmonary return line  188 , afterload  152 , and into reservoir  110 . 
     During systole (denoted by the arrows with the letter S in  FIGS. 3B and 3D ), the perfusate that entered the left ventricle during diastole is pumped out the aorta  220 . During systole, although the first pump  131  is providing a backpressure against the aorta via aortic line  184 , the pressure exerted by the heart  200  during systole is sufficient to overcome that backpressure, and perfusate is caused to flow out of the aorta and into aortic line  184 , which then flows through one-way valve  192  into reservoir  110 . As depicted in  FIG. 3B , the perfusate flows from the aorta  220  to aortic line  184 , and then through reservoir return line  186  to valve  192 . As depicted in  FIG. 3D , the perfusate flows from the aorta  220  to aortic line  184 , and then through second return line  1860 , to reservoir return line  187 , and then to valve  192 . 
     It should be noted that in some embodiments, during systole, some of the perfusate in aortic line  184  being pumped by first pump  131  is still travelling in the direction of heart  200 . Thus, although the fluid expelled by the heart  200  during systole travels in a reverse direction to the fluid being pumped by first pump  131 , some of that pumped fluid nevertheless is able to reach the aorta, and thus a flow of fluid to the coronary arteries  225 , heart tissue  230 , and coronary veins  235  is maintained throughout the pump-supported working mode. 
     It should be appreciated that in some embodiments, during diastole, a low volume or possibly no perfusate is likely to flow into reservoir return line  186  (in the case of  FIG. 3B ) or second return line  1860  (in the case of  FIG. 3D ). In some embodiments, the perfusate continues following aortic line  184  downward. However, during systole, the fluid being pumped out of heart  200  via the aorta causes perfusate to build up in aortic line  184 , which results in the expelled fluid flowing out of the aorta with sufficient pressure to travel up aortic line  184  in the ‘S’ direction, and ultimately into reservoir return line  186  (in  FIG. 3B ) or second return line  1860  (in  FIG. 3D ) and then into reservoir  110 . 
     In some embodiments, in pump-supported working mode, reservoir clamp  141  is in an open position, allowing perfusate to be pumped by second pump  132 . Perfusate then flows via right-side line  189  to connection  205  of heart  200 . In some embodiments, connection  205  corresponds to the right atrium of heart  200 . In some embodiments, second pump  132  is a centrifugal pump. In some embodiments, second pump  132  has a rotation speed of approximately 500 rpm. It will be appreciated that the rotational speed of second pump  132  can be adjusted to achieve target conditions. In some embodiments, the right atrium is loaded with a pressure of approximately 5 to 10 mmHg. The portion of perfusate pumped by second pump  132  is then pumped back to reservoir  110  via pulmonary return line  188  and afterload  152 . 
     As depicted in  FIGS. 3A, 3B, 3C and 3D , pump-supported working mode includes reservoir clamp  141  being set to an open state, and second pump  132  being activated. It should be noted that in some embodiments, in pump-supported working mode, reservoir clamp  141  is closed and second pump  132  is not operational. 
     The pump-supported working mode may provide the ability to evaluate contractile function of heart  200  with a reduced risk of the aortic pressure falling to an unacceptable level (in the event that there is poor contraction) because the first pump  132  assists with the maintenance of diastolic pressure so that the coronary arteries  225  remain perfused. The pump-supported working mode may provide conditions which are closer to simulating physiological conditions compared to Langendorff mode because the heart  200  is loaded. 
     In some embodiments, system  100  is further operable to switch to a passive working mode.  FIG. 4A  is a block diagram of the example system  100  of  FIG. 1A  configured to operate in a passive working mode.  FIG. 4C  is a block diagram of the example system  100  of  FIG. 1B  configured to operate in a passive working mode. 
     In  FIGS. 4A and 4C , in passive working mode, aortic line clamp  142  is closed, thereby preventing fluid communication between left-side line  182  and aortic line  184 . Left atrial clamp  143  is open, thereby allowing fluid to flow from left-side line  182  to left atrial line  183 . Priming clamp  146  is closed. In  FIG. 4A , reservoir return clamp  145  is closed and bypass clamp  144  is open, thereby causing perfusate to flow from aortic line  184  to reservoir return line  186 , then bypass line  185 , and then reservoir return line  186  into valve  192  and reservoir  110 . In  FIG. 4C , second return clamp  149  is closed, thereby preventing fluid from flowing through second return line  1860 . First return clamp  148  is open, thereby allowing fluid to flow from aortic line  184  into first return line  1850  and afterload  151 . 
       FIGS. 4B and 4D  are simplified block diagrams of the example systems of  FIGS. 4A and 4C  in operation, respectively, in which lines which do not carry fluids are not shown. As depicted, perfusate is drawn from reservoir  110  by first pump  131 . The perfusate is pumped through oxygenator  120  and filter  170 , and proceeds via one-way valve  191  to left-side line  182 . The perfusate in left-side line  182  flows entirely into left atrial line  183 . The fluid in left atrial line  183  then encounters variable resistor  160 , which may be used to control the left atrial pressure. In some embodiments, the left atrial pressure is approximately 5 to 10 mmHg. In some embodiments, the first pump  131  is a centrifugal pump. In some embodiments, the first pump  131  has a rotational speed of approximately 700 rpm. It will be appreciated that the rotational speed of first pump  131  in passive working mode can be adjusted to achieve a desired pressure. 
     The perfusate flows to connection  210  after variable resistor  160 . In some embodiments, connection  210  corresponds to the left atrium of heart  200 . The left atrium fills with perfusate, which is pumped by heart  200  to the left ventricle. The perfusate in the left ventricle is then pumped out via the aorta and into aortic line  184 . Unlike the Langendorff and pump-supported working modes, in passive working mode, no portion of the perfusate pumped by the first pump  131  is pumped through aortic line  184  to apply a pressure at the aortic valve of heart  200 . 
     During systole, the pressure is elevated, and some of the perfusate pumped out of the left ventricle of heart  200  takes a lower resistance path via the coronary arteries  225 , heart tissue  230 , and coronary veins  235 . As depicted in  FIG. 4B , during systole, most of the perfusate pumped from the left ventricle into aortic line  184  also flows to afterload  151  via reservoir return line  186  and bypass line  185 . As depicted in  FIG. 4D , during systole, most of the perfusate pumped from the left ventricle into aortic line  184  also flows to afterload  151  via first return line  1850 . Afterload  151  is operable to store energy in the form of elastic potential (for example, during systole). Thus, as the fluid is pumped from aortic line  184  to afterload  151  and ultimately to reservoir  110 , the afterload  151  stores potential energy. 
     During diastole, the pressure in aortic line  184  falls. Thus, the pressure in bypass line  185  (in the case of  FIG. 4B ) and first return line  185  (in the case of  FIG. 4D ) falls, and afterload  151  is operable to exert a pressure in aortic line  184  in the reverse direction, which applies a sufficient pressure at the aorta to cause the aortic valve to shut. Moreover, some of the perfusate in aortic line  184  is subjected to the pressure from afterload  151  toward the aorta. This pressure then causes some of the perfusate to flow through coronary arteries  225 , heart tissue  230 , and coronary veins  235 . In some embodiments, the negative pressure from afterload  151  during diastole may ensure that sufficient perfusate is circulated through heart tissues  230  so as to avoid or reduce the likelihood of damaging heart  200 . Thus, the heart tissues  230  may receive a sufficient amount of oxygenated perfusate throughout passive working mode for the heart  200  to function. 
     Optionally, in passive working mode, reservoir clamp  141  may be open, thereby allowing second pump  132  to pump some of the perfusate from reservoir  110 . Second pump  132  may then pump perfusate through right-side line  189  to a connection  205  of heart  200 . In some embodiments, connection  205  corresponds to the right atrium of heart  200 . In some embodiments, second pump  132  is a centrifugal pump. In some embodiments, second pump  132  operates at approximately 500 rpm, although a person skilled in the art will appreciate that the rotational speed can be adjusted to achieve a desired condition. In some embodiments, the second pump  132  is operable to load the right atrium of heart  200  with fluid at a pressure between approximately 5 and 10 mmHg. The fluid in the right atrium (i.e. the perfusate after having passed through heart tissue  230 ) is ultimately pumped from the right atrium to the right ventricle, which in turn is pumped out into pulmonary return line  188 . The fluids expelled into pulmonary return line  188  then pass via afterload  152 , and then into reservoir  110 . 
     Passive working mode may provide similar benefits to those outlined above with respect to pump-supported working mode. Passive working mode may offer additional potential benefits in that passive working mode may allow a more physiological perfusion of heart  200  because the systolic and diastolic pressures in the aorta can be controlled independently (i.e. to more closely match in vivo conditions, in some embodiments). Thus, in passive working mode, specific pressures can be applied to simulate heart performance for a particular patient. In pump-supported working mode, it may not be possible to control systolic and diastolic pressures in the aorta independently. In some embodiments, operating in passive working mode may also potentially result in one or more of reduced coronary and heart tissue damage, less edema, and better preservation, long-term viability and contractile function in heart  200 . 
     In some embodiments, system  100  is further operable to switch to right-sided working mode.  FIG. 5A  is a block diagram of the example system of  FIG. 1A  configured to operate in right-sided working mode.  FIG. 5B  is a block diagram of the example system of  FIG. 1B  configured to operate in a right-sided working mode. 
     As depicted in  FIGS. 5A and 5B , only reservoir clamp  141  and aortic clamp  142  are open in right-sided working mode. Thus, in  FIG. 5A , left atrial clamp  143 , bypass clamp  144 , reservoir return clamp  145  and priming clamp  146  are closed in right-sided working mode. Similarly, in  FIG. 5B  left atrial clamp  143 , first return clamp  148 , second return clamp  149  and priming clamp  146  are closed in right-sided working mode. Therefore, perfusate is drawn from reservoir  110  into both the first pump  131  and second pump  132 . Right-sided working mode may operate in a similar manner to Langendorff mode, but with the second pump  132  also in operation, relative to Langendorff mode described above (in which reservoir clamp  141  is closed and second pump  132  is not active).  FIG. 5C  is a simplified block diagram of the example systems of  FIGS. 5A and 5B  in operation in which lines which do not carry fluids are not shown. 
     Second pump  132  is operable to pump perfusate via right-side line  189  to a connection  205  of heart  200 . In some embodiments, connection  205  corresponds to the right atrium of heart  200 . In some embodiments, second pump  132  is a centrifugal pump. In some embodiments, second pump  132  operates with a rotational speed of approximately 500 rpm. In some embodiments, the second pump  132  loads the right atrium with fluid at a pressure between approximately 5 to 10 mmHg. It will be appreciated that the rotational speed of second pump  132  can be adjusted so as to achieve a desired operating condition. The perfusate is pumped out of the right ventricle to pulmonary return line  188 . The fluids in pulmonary return line  188  then pass through afterload  152 , and then to reservoir  110 . 
     First pump  131  is operable to pump perfusate through oxygenator  120 , filter  170 , and one-way valve  191  to left-side line  182 . Since left atrial clamp  143 , bypass clamp  144  and reservoir return clamp  145  are closed in right-sided working mode (and similarly in  FIG. 5B , left atrial clamp  143 , first return clamp  148  and second return clamp  149  are closed), all of the perfusate pumped by first pump  131  flows from left-side line  182  through to aortic line  184 , which connects to connection  220  of heart  200 . In some embodiments, connection  220  corresponds to the aorta of heart  200 . The aortic valve of heart  200  is a one-way valve and shuts when subjected to the pressure of the perfusate pumped from first pump  131 . The perfusate then travels into coronary arteries  225 , heart tissue  230 , and coronary veins  235 , ultimately draining into the right atrium of heart  200 . The perfusate then moves to the right ventricle, where the perfusate is pumped back to reservoir  110  via pulmonary return line  188  and afterload  152 . 
     Right-sided working mode may facilitate the collection of data relating to the functioning of the right side of a candidate heart  200 . Such data relating to the right side of heart  200  may provide important insights from a clinical perspective. 
     In some embodiments, system  100  further comprises a sampling line branching from the output of oxygenator  120  in any of Langendorff mode, pump-supported working mode, passive working mode, and right-sided working mode. The sampling line includes a one-way valve  193  which allows fluids to pass to sampling port  115 , and then back to reservoir  110 . 
     In each of Langendorff mode, pump-supported working mode, passive working mode, and right-sided mode, the presence of a line connecting aortic line  184  and pulmonary return line  188  is optional. In embodiments which include a line connecting aortic line  184  and pulmonary return line  188 , priming clamp  146  is provided. Such a line may be useful in priming system  100 , for example, to ensure that lines contain only liquids and no gases, and need not be present in any of the modes of operation described herein. In embodiments which include the line, priming clamp  146  is kept in the closed position for each of Langendorff mode, pump-supported working mode, passive working mode, and right-sided working mode. 
     Some embodiments of system  100  are operable to switch between any of Langendorff mode, pump-supported working mode, passive working mode, and right-sided mode. For example, switching from Langendorff mode to pump-supported working mode may be accomplished by first setting variable resistor  160  to provide elevated resistance. In some embodiments, variable resistor  160  is set to block all fluid flow. After tightening variable resistor  160 , left atrial clamp  143  is opened, thereby allowing passage of some perfusate from left-side line  182  to left atrial line  183 . The first pump  131  may then be adjusted so as to provide approximately 30 mmHg of pressure to the aorta (rather than the 50 mmHg described above in relation to an example embodiment). The variable resistor  160  can then be gradually loosened to allow perfusate to travel to the left atrium. The variable resistor  160  is adjusted such that perfusate is pumped into the left atrium at a pressure between approximately 5 to 10 mmHg. The left side of heart  200  would then be operating in working mode. It should be appreciated that the pressure values and rotational speed values given this example are merely examples and the system can be adjusted to use different values. 
     Optionally, reservoir clamp  141  can be switched from a closed position to an open position, such that a portion of the perfusate flows to second pump  132 . Second pump  132  will then begin pumping perfusate to the right atrium of heart  200 . The speed of second pump  132  can then be gradually increased until a desirable pressure level is reached (for example, between 5 to 10 mmHg in the right atrium). The system  100  would then be operating in full (also referred to herein as biventricular) pump-supported working mode, with both sides of heart  200  in operation. 
     In some embodiments, it may be desirable to adjust the pressure in various portions of the heart. For example, the right side of heart  200  can be loaded fully to the desired pressure, and the pressure at the left side of the heart can be kept low (for example, at 2 mmHg rather than the 5 to 10 mmHg described in connection with an example embodiment). Adjusting the pressures on different sides of the heart may facilitate functional evaluation and support of particular areas of the heart which may not otherwise be possible or convenient using conventional perfusion systems. 
     It will be appreciated that the system  100  may provide flexibility in testing various portions of the heart. For example, when reservoir clamp  141  is closed, no perfusate will flow to the right side of the heart (aside from incidental drainage from the coronary veins  235 ). Similarly, in some embodiments, first pump  131  pumps perfusate exclusively to the left side of heart  200  (through one or more of left atrial line  183  and aortic line  184 ), and second pump  132  pumps fluids exclusively to the right side of heart  200 . 
     As a further example, the system  100  shown in  FIG. 1B  can be transitioned from pump-supported working mode to passive working mode. Regardless of whether reservoir clamp  141  and second pump  132  are activated, in some embodiments, system  100  can be transitioned from pump-supported working mode to passive working mode by first opening first return clamp  148 , closing second return clamp  149  and closing aortic line clamp  142 . Closing aortic line clamp  142  causes all of the perfusate pumped by first pump  131  to be pumped through variable resistor  160  to the left atrium via left atrial line  183 . Thus, none of the perfusate flows down aortic line  184  to apply pressure to the aorta. However, with first return clamp  148  in an open state, afterload  151  stores energy as fluids pass through first return line  1850  during systole, and then afterload  151  releases stored energy and applies a reverse pressure to aortic line  184  during diastole to ensure that at least some backflow travels through the coronary arteries  225 , heart tissue  230 , and coronary veins  235 . 
     As a further example, system  100  can be transitioned from Langendorff mode to passive working mode. Relative to the system shown in  FIG. 1B , this transition can be accomplished by increasing the resistance of variable resistor  160  to a relatively high resistance and decreasing the pumping force of first pump  131 . Left atrial clamp  143  can be opened and aortic line clamp  142  can be closed, which allows fluid to flow to variable resistor  160  and stops fluid from flowing down aortic line  184 . First return clamp  148  is also opened, so as to allow perfusate to flow to first return line  1850  and afterload  151 . The first pump  131  and variable resistor  160  can then be adjusted so as to achieve the desired pressure at the left atrium of heart  200 . 
     As a further example, system  100  can be transitioned from passive working mode to Langendorff mode. Such a transition may be desirable if, for example, the heart  200  starts to fibrillate. Switching back to Langendorff mode may allow the heart  200  time to recover, and then return to working mode. Relative to the system shown in  FIG. 1B , this transition can be effected by, for example, closing first return clamp  148  and left atrial clamp  143 , and opening aortic line clamp  142 . The variable resistor  160  may be tightened prior to closing left atrial clamp  143 . 
     As a further example, system  100  can be transitioned from Langendorff mode to right-side working mode. This transition can be accomplished by opening reservoir clamp  141  and then gradually increasing the speed of second pump  132  until the desired pressure at the right atrium is achieved. 
     In some embodiments, system  100  can be transitioned from any one of Langendorff mode, pump-supported working mode, passive working mode, and right-sided working mode to any one of Langendorff mode, pump-supported working mode, passive working mode, and right-sided working mode. 
     In some embodiments, one or more of the systolic and diastolic pressures may be controlled by system  100 . For example, in pump-supported working mode, the variable resistor  160  and first pump  131  can be set to tailor a particular pressure for fluid flowing into the left atrium. Second pump  132  can be adjusted to control the pressure for fluid flowing into the right atrium. Thus, the systolic pressure for heart  200  can be controlled by adjusting the variable resistor  160 . Moreover, the diastolic pressure in system  100  can be controlled in the various modes of operation using one or more of the first pump  131  and afterload  151 . For example, decreasing the speed of first pump  131  would in turn decrease the pressure at the aorta in Langendorff mode, passive working mode, and right-sided working mode. As another example, selecting or modifying the afterload  151  in passive working mode allows the backpressure exerted by afterload  151  to be adjusted. For example, in the case of a spring-loaded piston being used as afterload  151 , a spring with a different spring constant k (or a different spring-loaded piston altogether) could be chosen so as to tailor the amount of backpressure applied during diastole. 
     In some embodiments, the adjusting of systolic and diastolic pressures may provide additional insight into the functioning of a candidate heart. For example, if a heart transplant candidate recipient suffers from hypertension (i.e. above-average blood pressure), a candidate heart  200  could be tested under elevated systolic and/or diastolic pressures to assess the likelihood that the heart  200  could perform suitably under elevated pressures. 
       FIG. 6  is a flow chart for an example method of performing a perfusion on a heart, according to some embodiments. 
     The method  600  begins at  602 , where a reservoir  110  is provided which contains fluid for delivery to heart  200 . At  604 , a first pump  131  is provided which is configured to deliver a portion of the fluid in the reservoir  110  to a left-side line  182 . In some embodiments, the first pump  131  is connected to the left-side line  182  via one or more of an oxygenator  120 , a filter  170 , and a one-way valve  191 . 
     At  606 , a left atrial line  183  is provided. The left atrial line  183  may be connected to the left-side line  182  via a left atrial line clamp  143 . The left atrial line  183  may be further connected to the left atrium of heart  200 . At  608 , an aortic line  184  is provided. The aortic line may be connected to the left-side line  182  via an aortic line clamp  142 . The aortic line  184  may be further connected to the aorta of heart  200 . 
     At  610 , a reservoir return line  186  is provided. In some embodiments, a bypass line  185  may be provided which is connected in parallel with the reservoir return line  186 . In some embodiments, bypass line  185  includes an afterload  151 . The reservoir return line  186  may be connected at a proximal end to the aortic line  184  via reservoir return clamp  145 . The reservoir return line  186  may be further connected at a distal end to reservoir  110 , possibly via one-way valve  192 . As used herein, a connection or part is described as being proximal when that connection or part is closer to heart  200  relative to a second connection or part, which is referred to as being distal. For example, the distal end of reservoir return line  186  is further away from heart  200  than the proximal end of reservoir return line  186 . Optionally, a separate first return line  1850  and second return line  1860  are provided, which are both connected at respective proximal ends to aortic line  184  (as depicted in  FIG. 1B ). In embodiments featuring lines  1850  and  1860 , lines  1850  and  1860  join to form reservoir return line  187 . 
     At  612 , a pulmonary return line  188  is provided. The pulmonary return line  188  may be connected at a distal end to reservoir  110 . The pulmonary return line  188  may be further connected at a proximal end to the pulmonary artery of heart  200 . 
     Optionally, in some embodiments, at  614 , a right side line  189  is provided. The right side line  189  may be connected to the right atrium of heart  200 . At  616 , a second pump  132  is provided. The second pump  132  may be connected to reservoir  132 . The second pump  132  may also be connected to right side line  189 . The second pump  132  may be configured to pump fluid from reservoir  110  to the right atrium of heart  200 . 
     The scope of the present application is not intended to be limited to the particular embodiments of the processes, machines, manufactures, compositions of matter, means, methods and steps described in the specification. As one of ordinary skill in the art will readily appreciate from the disclosure of the present invention, processes, machines, manufactures, compositions of matter, means, methods, or steps, presently existing or later to be developed, that perform substantially the same function or achieve substantially the same result as the corresponding embodiments described herein may be utilized. Accordingly, the appended claims are intended to include within their scope such processes, machines, manufactures, compositions of matter, means, methods, or steps. 
     As can be understood, the detailed embodiments described above and illustrated are intended to be examples only. Variations, alternative configurations, alternative components and modifications may be made to these example embodiments. The invention is defined by the claims.