Systems and methods for ex vivo lung care

Abstract

To provide methods and systems of maintaining, diagnosing, and providing therapy to a lung ex vivo.SOLUTION: A lung care system, as shown in the figure, involves: positioning the lung in an ex vivo perfusion circuit; circulating a perfusion fluid through the lung, the fluid entering the lung through a pulmonary artery interface and leaving the lung through a left atrial interface; and ventilating the lung by flowing a ventilation gas through a tracheal interface. Maintaining the lung for extended periods involves causing the lung to rebreathe a captive volume of air, and reaching an equilibrium state between the perfusion fluid and the ventilation gas. Diagnosing the gas exchange capability of the lung involves deoxygenating the perfusion fluid, and measuring a time taken to reoxygenate the perfusion fluid by ventilating the lung with an oxygenation gas.SELECTED DRAWING: Figure 22

Description

Technical Field

[0001] Reference to related applications This application claims the priority and benefits of U.S. Provisional Application No. 61 / 024,976, filed on January 31, 2008; U.S. Application No. 12 / 099,687, filed on April 8, 2008; U.S. Application No. 12 / 099,715, filed on April 8, 2008; U.S. Application No. 12 / 099,717, filed on April 8, 2008; U.S. Application No. 12 / 099,725, filed on April 8, 2008; and U.S. Application No. 12 / 099,728, filed on April 8, 2008, the entire contents of which are incorporated herein by reference.

[0002] Field of Invention The present invention generally relates to systems, methods, and devices for ex vivo organ care. More particularly, in various aspects, the present invention relates to a portable device for caring for, evaluating, and applying therapeutic measures to a single lung or a pair of lungs ex vivo under physiological or near-physiological conditions.

Background Art

[0003] Background of the Invention Current organ preservation techniques typically involve the cryopreservation of organs in chemical preservation solutions on ice. These techniques utilize various solutions, none of which adequately protect the organs from damage due to ischemia. Such damage is particularly undesirable when the organs are intended for transplantation from a donor to a recipient.

[0004] Effective physiological preservation of ex vivo organs may offer significant advantages over conventional approaches. For example, physiological ex vivo preservation may allow for more careful monitoring, functional testing, evaluation, and treatment of retrieved organs. This could enable earlier detection and potential repair of defects in retrieved organs, further reducing the likelihood of organ failure after transplantation. The ability to perform and evaluate simple repairs to organs may also allow for the preservation of many organs with minor defects, while current transplantation techniques necessitate their discarding. This is critically important when retrieving lungs, as they are easily damaged even before retrieval within the donor's body.

[0005] Furthermore, more effective matching between organs and specific recipients can be achieved, further reducing the likelihood of eventual organ rejection. Current transplantation techniques primarily rely on matching donor and receptor blood types, but this matching itself is relatively unreliable as an indicator of whether or not the recipient will reject the organ. A more preferred test for organ compatibility is human leukocyte antigen (HLA) matching, but current cold-ischemic organ preservation approaches hinder the use of this test, which often takes more than 12 hours to complete.

[0006] When using conventional approaches, ischemia-induced damage increases as a function of the length of time an organ is preserved ex vivo. For example, typically, lungs can only be preserved ex vivo for about 6 to 8 hours before becoming unusable for transplantation. Typically, hearts can only be preserved ex vivo for about 4 to 6 hours before becoming unusable for transplantation. These relatively short periods limit the number of recipients reachable from a given donor site, thereby limiting the recipient pool for the retrieved organ. Even within the time limit, organs can still be significantly damaged. A major problem is that there may be no observable signs of damage. Therefore, transplanting suboptimal organs can lead to post-transplant organ failure or other damage. Thus, it may be desirable to develop techniques that can extend the time that organs can be preserved in a healthy state ex vivo. Such techniques could reduce the risk of post-transplant organ failure and expand the pool of potential donors and recipients.

[0007] Long-term, reliable ex vivo organ care may also offer benefits outside the context of organ transplantation. For example, typically, a patient's body as a whole may tolerate far lower levels of chemotherapy, biotherapy, and radiation therapy than many specific organs. Ex vivo organ care systems can reduce the risk of damage to other parts of the body by allowing organs to be removed from the body and treated in isolation.

[0008] In light of the above, there is a need for improved systems, methods, and devices for organ care using ex vivo. [Overview of the project]

[0009] The present invention addresses the current shortcomings of the art by providing, in various embodiments, improved systems, methods, solutions, and apparatus for portable ex vivo organ care.

[0010] Generally, in one aspect, the present invention features a lung care system comprising a lung chamber assembly comprising a portable multi-purpose module including a portable chassis, a single-purpose disposable module with an interface adapted to couple the single-purpose disposable module and the multi-purpose module for electromechanical interaction with the multi-purpose module; and a lung chamber assembly comprising a lung chamber assembly comprising a lung chamber assembly comprising a dual drain system for transporting the flow of perfusion fluid away from the lung, comprising a dual drain system comprising a measuring drain for directing a portion of the perfusion fluid flow to a sensor for measuring the perfusion fluid gas content and a main drain for receiving the remainder of the perfusion fluid flow. In one aspect, the lung care system comprises a drainage system for draining perfusion fluid from the lung chamber assembly, wherein the drainage system comprises a measuring conduit and a main drain conduit, and the measuring conduit further directs the flow of perfusion fluid to a sensor adapted to measure the perfusion fluid gas content.

[0011] Other embodiments include one or more of the following features: A dual drain includes a container for receiving perfusion fluid flow, and overflow from the container flows into a primary drain. The system includes a pump for circulating the perfusion fluid and a ventilation system for ventilating the lungs with a gas having a predetermined composition. The gas includes oxygen and carbon dioxide. A portable multi-purpose module includes a lung console for providing at least one of electrical, pneumatic, and mechanical control of a disposable module, the lung console including a ventilation controller for controlling lung ventilation and a mechanical actuator for operating bellows that cause gas flow to the lungs. The lung console pneumatic control system controls one or more valves in the ventilation gas circuit connected to the lungs in the disposable module. The pneumatic control system controls at least one of a bellows valve for blocking flow between the lungs and the bellows, a relief valve for supplying ventilation gas, and a trickle valve for introducing gas into the ventilation gas circuit. The ventilation controller selects the gas to be used for lung ventilation from one of an oxygenating gas, a deoxygenating gas, and a maintenance gas. The oxygenating gas is air or a gas containing 25% to 100% oxygen. The deoxygenation gas is composed of carbon dioxide and nitrogen, and the maintenance gas is composed of oxygen, carbon dioxide, and nitrogen. In one embodiment, the deoxygenation gas is approximately 6% carbon dioxide and approximately 94% nitrogen, and the maintenance gas is approximately 12% oxygen, approximately 5.5% carbon dioxide, and approximately 82.5% nitrogen. The multi-purpose module includes a perfusion fluid controller capable of controlling the levels of gas content, such as oxygen, in the perfusion fluid. The perfusion fluid controller controls the gas components of the perfusion fluid by, for example, controlling the flow of gas to a gas exchanger that exchanges gas between the gas flow and the perfusion fluid. The gas flowing into the gas exchanger is the deoxygenation gas, which removes oxygen from the perfusion fluid. The multi-purpose monitor includes a monitor for displaying the status of the lung care system, the status including information on the oxygen content of the perfusion fluid entering and leaving the lungs. It also displays real-time tracking of ventilation gas pressure and pulmonary artery pressure.

[0012] In general, in another aspect, the present invention features a single-use disposable module comprising a lung chamber assembly having an interface adapted for attachment to a multi-use module, and a first interface for enabling the flow of perfusion fluid into the lungs and a second interface for enabling ventilation of the lungs with a ventilation gas; and a lung care module comprising a drain system for discharging the flow of perfusion fluid from the lung chamber assembly, comprising a measuring conduit and a main drain conduit, the drain system further directing the flow of perfusion fluid to a sensor adapted so that the measuring conduit measures the perfusion fluid gas content.

[0013] Other embodiments include one or more of the following features: The module includes a system for ventilating the lungs with one of a maintenance gas, an evaluation gas, and an oxygenated gas such as air. The system may be configured to rebreathe a certain amount of gas into the lungs. The ventilation system ventilates the lungs with a maintenance gas having a composition of about 12% oxygen, about 5.5% carbon dioxide, and about 82.5% nitrogen. The lungs are ventilated using mechanically actuated bellows. The ventilation system further includes a trickle valve for introducing a flow of maintenance gas and a relief valve for ventilating excess gas. A second interface to the lungs includes a tracheal cannula having an insertion section for insertion into the trachea and a connector section for connection to a ventilation gas circuit. A first interface to the lungs includes a pulmonary artery cannula having an insertion section for insertion into the pulmonary artery and a connector section for connection to a perfusion fluid circuit. It also includes a pressure transducer connector that defines an opening to a lumen of the connector section near the insertion tube in order to position a pressure transducer near the point of inflow of perfusion fluid into the lungs. The pressure transducer connector provides an additional channel for remote ventilation in the pressure transducer.

[0014] In general, in yet another aspect, the present invention features a lung chamber assembly comprising: a housing having a bottom surface and walls including at least one housing drain; a support surface for supporting the lung, the support surface defining a drain for discharging perfusion fluid from the lung, and a drainage channel leading to the drain; an openable lid providing a sealable connection to the wall surface of the housing; a first interface for enabling the flow of perfusion fluid into the lung; a second interface for enabling ventilation of the lung; and a third interface for enabling the flow of perfusion fluid away from the lung.

[0015] Other embodiments include one or more of the following features: The housing is a drain system for transporting a flow of perfusion fluid away from the lung, and includes a measuring drain for directing a portion of the perfusion fluid flow to a sensor of perfusion fluid gas content, and a main drain for receiving the remainder of the perfusion fluid flow. The drain system has a region for collecting the flow of perfusion fluid away from the lung into a pool that supplies to the measuring drain, the measuring drain having a drainage capacity less than the flow rate of perfusion fluid away from the lung. The flow of perfusion fluid overflowing from the region flows into the main drain. In some embodiments, the drain system further includes a wall surface that partially surrounds the measuring drain, partially blocking the flow of perfusion fluid from the measuring drain to the main drain, and facilitating the formation of a pool of perfusion fluid above the measuring drain. The lung chamber housing defines an opening that gives sealed passages through the housing for the pulmonary artery cannula, pulmonary artery pressure transducer conduit, and tracheal cannula. In some embodiments, the perfusion fluid exits the lung through an exposed left atrial cuff and flows into a drainage system. In other embodiments, the flow of perfusion fluid exiting the lung passes through a sealed connection to the left atrial cuff, which is connected to a conduit that carries the perfusion fluid away from the lung. A portion of the perfusion fluid flow passes through an oxygen content sensor, and the remainder flows into a reservoir.

[0016] In general, in further aspects, the present invention features a method for diagnosing the lungs, comprising the steps of: positioning the lungs within an ex vivo perfusion circuit; circulating a perfusion fluid into the lungs through a pulmonary artery interface and out of the lungs through a left atrial interface; ventilating the lungs by flowing a ventilation gas through a tracheal interface; deoxygenating the perfusion fluid until it reaches a predetermined first value of oxygen content in the perfusion fluid; reoxygenating the perfusion fluid by ventilating the lungs with an oxygenated gas until it reaches a predetermined second value of oxygen content in the perfusion fluid; and determining the state of the lungs based on the time required for the lungs to change the oxygen content level in the perfusion fluid from a first value to a second value of oxygen content.

[0017] Other embodiments include one or more of the following features: The perfusion fluid is deoxygenated by ventilating the lungs with a ventilation gas containing carbon dioxide and nitrogen, for example, about 5.5% carbon dioxide and about 94.5% nitrogen. The perfusion fluid is deoxygenated by circulating the perfusion fluid through a gas exchange device, which is in fluid communication with a deoxygenation gas containing carbon dioxide and nitrogen, and which modifies the oxygen composition in the perfusion fluid by gas exchange between the ventilation gas and the perfusion fluid. A predetermined first value of oxygen content corresponds to an erythrocyte saturation of about 73%. The oxygenation gas is air or a gas containing about 25% to about 100% oxygen. A predetermined second value of oxygen content corresponds to an erythrocyte saturation of about 93%. The perfusion fluid flows at a rate of about 1.5 liters per minute and is heated to a near-physiological temperature level by a heater. The perfusion fluid is composed of whole blood or blood products such as blood that is partially depleted of leukocytes or platelets. Various therapeutic agents are delivered to the lungs via the perfusion fluid during perfusion, or through the tracheal interface using a nebulizer or bronchoscope. The oxygen level in the perfusion fluid is measured using a pulse oximeter, which determines the red blood cell saturation in the fluid.

[0018] In general, in further aspects, the present invention features a method for preserving the lung ex vivo, comprising the steps of: circulating a perfusion fluid to the lung that enters the lung through a pulmonary artery interface and leaves the lung through a left atrial interface; ventilating the lung through a tracheal interface by flowing a captive volume of ventilation gas back and forth between the lung and a variable volume chamber; and maintaining a predetermined composition of the ventilation gas and a minimum gas pressure of the captive volume by introducing a further amount of ventilation gas into the captive volume and passing excess ventilation gas from the captive volume.

[0019] Other embodiments include one or more of the following features: The ventilation gas comprises a composition of inert gases such as oxygen, carbon dioxide, and nitrogen. The perfusion fluid reaches an equilibrium level corresponding to a given composition of the ventilation gas. The given composition of the ventilation gas contains approximately 5-20% oxygen and approximately 2-10% carbon dioxide. The gas content of the perfusion fluid reaches an equilibrium level with a hemoglobin saturation level of approximately 88-98%.

[0020] The predetermined composition of the ventilation gas contains approximately 12% oxygen and approximately 5.5% carbon dioxide. The hemoglobin saturation level of the perfusion fluid entering the lungs reaches an equilibrium level of approximately 90-95%, and the hemoglobin saturation level of the perfusion fluid leaving the lungs also reaches an equilibrium level of approximately 90-95%. The oxygen content of the perfusion fluid entering the lungs is lower than the physiological level, and the oxygen content of the perfusion fluid leaving the lungs is higher than the physiological level. The following parameters are used in certain embodiments: the further flow of ventilation gas is approximately 400-600 mL per minute, the collection volume is approximately 400-1200 mL, the minimum gas pressure of the collection volume is approximately 4-8 cmH₂O, and the maximum ventilation gas pressure is approximately 12-22 cmH₂O. Excess ventilation gas is vented through a relief valve communicating with the collection volume. The variable volume chamber is a bellows, and compressing the bellows causes the ventilation gas to flow into the lungs. The pulmonary artery interface includes a pulmonary artery cannula, the portion of which is inserted into the pulmonary artery of the lung. The perfusion fluid flows away from the lung through the exposed left atrial cuff of the lung, or through a sealed or semi-sealed connection between the left atrial cuff and the left atrial cannula. The tracheal interface includes a tracheal cannula, the portion of which is inserted into the trachea of ​​the lung. The method includes a step of measuring a first level of oxygen content in the perfusion fluid flowing into the lung and a second level of oxygen content in the perfusion fluid flowing out of the lung. The oxygen measurement step includes measuring at least one of the levels of oxygen saturation of hemoglobin in the perfusion fluid and the partial pressure of oxygen in the perfusion fluid flowing into and out of the lung. The perfusion fluid may contain blood products that can deliver therapeutic drugs to the lung. Gas exchange in the lung between the ventilation gas and the perfusion fluid brings the levels of one or more gases, such as oxygen and carbon dioxide, in the perfusion fluid to equilibrium. The lung can be preserved for approximately 3 to 24 hours when maintained at equilibrium gas levels. [Invention 1001] Portable multi-purpose module including portable chassis; Interfaces adapted to connect single-purpose disposable modules and multi-purpose modules for electromechanical interaction with multi-purpose modules; and A lung chamber assembly having a first interface for enabling the flow of perfusion fluid to the lungs, a second interface for enabling ventilation of the lungs by ventilation gas, and a third interface for enabling the flow of perfusion fluid away from the lungs, the lung chamber assembly including a dual drain system for transporting the flow of perfusion fluid away from the lungs, the dual drain system including a measurement drain for directing a portion of the perfusion fluid flow towards a sensor of the perfusion fluid gas content and a main drain for receiving the remaining portion of the perfusion fluid flow. A single-use disposable module and a [Invention 1002] The dual drain further includes a container for collecting the flow of perfusion fluid away from the lungs in a pool that supplies the measurement drain, the drainage capacity of the measurement drain being less than the flow rate of the perfusion fluid away from the lungs, and excess perfusion fluid overflowing from the container flowing to the main drain, the system of Invention 1001. [Invention 1003] The disposable module further includes a pump adapted to circulate perfusion fluid to the lungs, the system of Invention 1001. [Invention 1004] The system of Invention 1001 further includes a ventilation system connected to the second interface for ventilating the lungs with a gas having a predetermined composition. [Invention 1005] The system of Invention 1004, wherein the predetermined composition includes about 12% oxygen. [Invention 1006] The system of Invention 1004, wherein the predetermined composition is about 12% oxygen, about 5.5% carbon dioxide and about 82.5% nitrogen. [Invention 1007] The system of Invention 1001 further includes a conduit providing fluid communication between the main drain and a reservoir for perfusion fluid. [Invention 1008] The portable multi-use module includes a lung console for providing at least one of electrical control, pneumatic control and mechanical control of the disposable module, the system of Invention 1001. [The present invention 1009] The system of the present invention 1008, wherein the lung console includes a ventilation controller for controlling the ventilation of the lung. [The present invention 1010] The system of the present invention 1009, wherein the ventilation controller includes a mechanical actuator for operating a bellows for causing a flow of ventilation gas to the lung. [The present invention 1011] The system of the present invention 1009, wherein the lung console module includes a pneumatic control system for controlling at least one valve in a ventilation gas circuit connected to the lung in a disposable module. [The present invention 1012] The system of the present invention 1011, wherein at least one valve is disposed in an off position of a valve that closes a ventilation gas circuit between the lung and the bellows, i.e., a gas connection between the lung and the bellows. [The present invention 1013] The system of the present invention 1011, wherein at least one valve includes a relief valve for venting ventilation gas from the lung ventilation circuit. [The present invention 1014] The system of the present invention 1011, wherein at least one valve includes a trickle valve for introducing ventilation gas into the ventilation gas circuit. [The present invention 1015] The system of the present invention 1009, wherein the ventilation controller is capable of selecting one of a plurality of gases for ventilating the lung. [The present invention 1016] The system of the present invention 1015, wherein the plurality of gases includes an oxygenated gas, a deoxygenated gas, and a maintenance gas. [The present invention 1017] The system of the present invention 1016, wherein the oxygenated gas is selected from a set consisting of air and a gas containing 25% to 100% oxygen. [The present invention 1018] The system of the present invention 1016, wherein the deoxygenated gas includes carbon dioxide and nitrogen. [The present invention 1019] The system of the present invention 1016, wherein the deoxygenated gas is composed of approximately 6% carbon dioxide and approximately 94% nitrogen. [Invention 1020] The system of the present invention 1016, wherein the maintenance gas contains oxygen, carbon dioxide, and nitrogen. [Invention 1021] The system of the present invention 1016, wherein the maintenance gas is composed of approximately 12% oxygen, approximately 5.5% carbon dioxide, and approximately 82.5% nitrogen. [Invention 1022] The system of the present invention 1016, wherein the maintenance gas is supplied from a tank housed within a multi-purpose module. [Invention 1023] A system according to the present invention 1008, comprising a portable multi-purpose module including a perfusion fluid controller for controlling the gaseous components of the perfusion fluid. [Invention 1024] A system according to the present invention 1023, wherein a perfusion fluid controller includes a pneumatic valve controller for controlling the flow of gas to a gas exchanger in a disposable module, and the gas exchanger is configured to exchange gas between the gas flow to the gas exchanger and the perfusion fluid. [Invention 1025] The system of the present invention 1024, wherein the gas flow to the gas exchanger includes a deoxygenating gas for removing oxygen from the perfusion fluid. [Invention 1026] The system of the present invention 1025, wherein the deoxygenation gas contains carbon dioxide and nitrogen. [Invention 1027] The system of the present invention 1025, wherein the deoxygenated gas is composed of approximately 6% carbon dioxide and approximately 94% nitrogen. [Invention 1028] A system according to the present invention 1001, wherein a multipurpose module includes a monitor for displaying the status of the lung care system and a user interface for controlling the operation of the lung care system. [Invention 1029] The system of the present invention 1028, wherein the displayed status includes at least one of the oxygen content of the perfusion fluid entering the lungs and the oxygen content of the perfusion fluid leaving the lungs. [Invention 1030] The system of the present invention 1028, wherein the monitor displays real-time tracking of the ventilation gas pressure at the point where the gas enters the lungs, real-time tracking of the pulmonary artery pressure in the lungs measured by a pressure sensor located at the point where the perfusion fluid enters the pulmonary artery, and a time-averaged graph of the pulmonary artery pressure. [Invention 1031] The system of the present invention 1001, wherein a multipurpose module includes a monitor for displaying the status of the lung care system during lung assessment and a user interface for controlling the operation of the lung care system, the monitor displaying real-time tracking of the oxygen content of the perfusion fluid entering the lung and real-time tracking of the oxygen content of the perfusion fluid leaving the lung. [Invention 1032] Portable multi-purpose module including portable chassis and lung console; Interfaces adapted to connect single-purpose disposable modules and multi-purpose modules for electromechanical interaction with multi-purpose modules; and A lung chamber assembly having a first interface for enabling the flow of perfusion fluid into the lung, a second interface for enabling ventilation of the lung with a ventilation gas, and a third interface for enabling the flow of perfusion fluid away from the lung, Includes single-use disposable modules, The lung console provides at least one of the following controls for the perfusion fluid and ventilation gas of the disposable module: electrical control, pneumatic control, and mechanical control. Lung care system. [Invention 1033] The system of the present invention 1032, wherein the lung chamber assembly includes a dual drain system for transporting a flow of perfusion fluid away from the lung, the dual drain system comprising a measuring drain for directing a portion of the perfusion fluid flow to a sensor for perfusion fluid gas content and a main drain for receiving the remainder of the perfusion fluid flow. [Invention 1034] The system of the present invention 1033, further comprising a dual drain for collecting the flow of perfusion fluid away from the lungs into a pool that supplies to a measuring drain, wherein the drainage capacity of the measuring drain is less than the flow rate of perfusion fluid away from the lungs, and the excess perfusion fluid overflowing from the container flows into a primary drain. [Invention 1035] The system of the present invention 1032 further includes a disposable module that further comprises a pump adapted to circulate perfusion fluid to the lungs. [Invention 1036] The system of the present invention 1032 further includes a disposable module which further comprises a ventilation system connected to a second interface for ventilating the lungs with a gas having a predetermined composition. [Invention 1037] A system according to the present invention 1036, wherein the predetermined composition contains approximately 12% oxygen. [Invention 1038] A system according to the present invention 1036, wherein the predetermined composition is approximately 12% oxygen, approximately 5.5% carbon dioxide, and approximately 82.5% nitrogen. [Invention 1039] The system of the present invention 1033, wherein the main drain directs the remaining portion of the perfusion fluid to a reservoir. [Invention 1040] A system according to the present invention 1032, wherein the lung console includes a ventilation controller for controlling lung ventilation. [Invention 1041] A system according to the present invention 1040, wherein the ventilation controller includes a mechanical actuator for operating a bellows to cause a flow of ventilation gas to the lungs. [Invention 1042] The system of the present invention 1040, wherein the lung console module includes a pneumatic control system for controlling at least one valve in a ventilation gas circuit connected to the lung in a disposable module. [Invention 1043] The system of the present invention 1042, wherein at least one valve is positioned in the off position of the valve that closes the ventilation gas circuit between the lung and the bellows, i.e., the fluid connection between the lung and the bellows. [Invention 1044] A system according to the present invention 1042, wherein at least one valve includes a relief valve for allowing ventilation gas to pass from a lung ventilation circuit. [Invention 1045] A system according to the present invention 1042, wherein at least one valve includes a trickle valve for delivering ventilation gas to a ventilation gas circuit. [Invention 1046] A system according to the present invention 1040, wherein the ventilation controller is configured to select one of several gases for ventilating the lungs. [Invention 1047] A system according to the present invention 1046, wherein multiple gases include an oxygenating gas, a deoxygenating gas, and a maintenance gas. [Invention 1048] The system of the present invention 1047, wherein the oxygenation gas is selected from a set consisting of air and gases containing 25% to 100% oxygen. [Invention 1049] The system of the present invention 1047, wherein the deoxygenation gas contains carbon dioxide and nitrogen. [Invention 1050] The system of the present invention 1047, wherein the deoxygenated gas is composed of approximately 6% carbon dioxide and approximately 94% nitrogen. [Invention 1051] The system of the present invention 1047, wherein the maintenance gas comprises oxygen, carbon dioxide, and nitrogen. [Invention 1052] The system of Invention 1047, wherein the maintenance gas is composed of approximately 12% oxygen, approximately 5.5% carbon dioxide, and approximately 82.5% nitrogen. [Invention 1053] The system of the present invention 1047, wherein the maintenance gas is supplied from a tank housed within a multi-purpose module. [Invention 1054] A system according to the present invention 1032, wherein the lung console includes a perfusion fluid controller for controlling the gas components of the perfusion fluid. [Invention 1055] A system according to the present invention 1054, wherein a perfusion fluid controller includes a pneumatic valve controller for controlling the flow of gas to a gas exchanger in a disposable module, and the gas exchanger is configured to exchange gas between the gas flow to the gas exchanger and the perfusion fluid. [Invention 1056] The system of the present invention 1055, wherein the gas flow to the gas exchanger includes a deoxygenating gas for removing oxygen from the perfusion fluid. [Invention 1057] A system according to the present invention 1056, wherein the deoxygenation gas contains carbon dioxide and nitrogen. [Invention 1058] The system of the present invention 1056, wherein the deoxygenated gas is composed of approximately 6% carbon dioxide and approximately 94% nitrogen. [Invention 1059] The system of the present invention 1032, wherein the multipurpose module includes a monitor for displaying the status of the lung care system and a user interface for controlling the operation of the lung care system. [Invention 1060] The system of the present invention 1059, wherein the displayed status includes at least one of the oxygen content of the perfusion fluid entering the lungs and the oxygen content of the perfusion fluid leaving the lungs. [Invention 1061] The system of the present invention 1059, wherein the monitor displays real-time tracking of the ventilation gas pressure at the point where the gas enters the lungs, real-time tracking of the pulmonary artery pressure in the lungs measured by a pressure sensor located at the point where the perfusion fluid enters the pulmonary artery, and a time-averaged graph of the pulmonary artery pressure. [Invention 1062] The system of the present invention 1032, comprising a multipurpose module including a monitor for displaying the status of the lung care system during lung assessment and a user interface for controlling the operation of the lung care system, wherein the monitor displays real-time tracking of the oxygen content of the perfusion fluid entering the lung and real-time tracking of the oxygen content of the perfusion fluid leaving the lung. [Invention 1063] A versatile module including a chassis; Interface adapted for mounting on multi-purpose modules; A lung chamber assembly having a first interface for enabling the flow of perfusion fluid into the lungs, a second interface for enabling ventilation of the lungs with a ventilation gas, and a third interface for enabling the flow of perfusion fluid away from the lungs; and A drain system for discharging perfusion fluid from a lung chamber assembly, comprising a measuring conduit and a main drain conduit, wherein the measuring conduit further directs the flow of perfusion fluid to a sensor adapted to measure the perfusion fluid gas content, Single-use disposable modules and A lung care system, including... [Invention 1064] The system of the present invention 1063, wherein the measuring conduit is adapted to position the perfusion fluid under conditions suitable for measuring the gas content by a sensor. [Invention 1065] The system of the present invention 1063, wherein the perfusion fluid gas content is equal to the oxygen content. [Invention 1066] A system according to the present invention 1063, wherein the sensor is a pulse oximeter. [Invention 1067] Interfaces suitable for mounting on multi-purpose modules, and A lung chamber assembly having a first interface for enabling the flow of perfusion fluid into the lungs and a second interface for enabling ventilation of the lungs with a ventilation gas, Single-use disposable modules; A drain system for discharging perfusion fluid flow from a lung chamber assembly, comprising a measuring conduit and a main drain conduit, wherein the measuring conduit further directs the perfusion fluid flow to a sensor adapted to measure the perfusion fluid gas content. A lung care module, including... [Invention 1068] A module of the present invention 1067, further comprising a ventilation system connected to a second interface for ventilating the lungs with gas. [Invention 1069] A module according to the present invention 1068, wherein the gas can be selected from a plurality of gases, each having a predetermined composition. [Invention 1070] A module according to the present invention 1069, comprising multiple gases, including a maintenance gas, an evaluation gas, and air. [Invention 1071] A module according to the present invention 1070, wherein the predetermined composition of the maintenance gas contains approximately 12% oxygen. [Invention 1072] A module according to the present invention 1070, wherein the predetermined composition of the maintenance gas is approximately 12% oxygen, approximately 5.5% carbon dioxide, and approximately 82.5% nitrogen. [Invention 1073] A module of the present invention 1068, wherein the ventilation system may be configured to rebreathe a certain amount of maintenance gas into the lungs. [Invention 1074] A module of the present invention 1073, wherein the ventilation system includes an isolation volume compartment, and the amount of maintenance gas is circulated between the lungs and the isolation volume compartment. [Invention 1075] A module of the present invention 1073, wherein the ventilation system includes a bellows, and by operating the bellows, the aforementioned amount of maintenance gas is circulated between the lungs and the bellows. [Invention 1076] A module of the present invention 1073, wherein the ventilation system includes a connection to an external source of maintenance gas via a trickle valve, the trickle valve maintaining a predetermined composition of the maintenance gas within the ventilation system by releasing gas into the ventilation system. [Invention 1077] A module of the present invention 1068, further comprising a relief valve that maintains a minimum gas pressure in the lungs as part of the ventilation system. [Invention 1078] A module according to the present invention 1070, wherein the predetermined composition of the evaluation gas contains approximately 6% carbon dioxide. [Invention 1079] A module of the present invention 1070, wherein the evaluation gas has a predetermined composition containing approximately 4-7% carbon dioxide and approximately 93-97% nitrogen. [Invention 1080] A module of the present invention 1067, wherein the second interface includes a tracheal cannula. [Invention 1081] A module of the present invention 1080, comprising a tracheal cannula including a tracheal insertion section for insertion into the trachea, a flexible section, a locking mechanism for securing the tracheal cannula to a lung chamber assembly, and a ventilation device connector section. [Invention 1082] A module of the present invention 1081, wherein the tracheal insertion section has a diameter of approximately 0.65 inches to 0.95 inches. [Invention 1083] A module of the present invention 1081, which can seal off gas flow to and from the lungs by clamping a flexible portion. [Invention 1084] A module of the present invention 1067 further includes a pump adapted to flow perfusion fluid to and from the lungs. [Invention 1085] A module of the present invention 1084 further includes a heater that is in thermal contact with the perfusion fluid to maintain the temperature of the perfusion fluid near physiological levels. [Invention 1086] A module according to the present invention 1085, wherein the temperature is approximately 30°C to 37°C. [Invention 1087] A module according to the present invention 1085, wherein the temperature is approximately 34°C to 37°C. [Invention 1088] A module of the present invention 1084, further comprising a gas exchange device in fluid communication with at least one gas supply source and a perfusion fluid, the gas exchange device being adapted to controllably adjust the composition of a first gas component in the perfusion fluid. [Invention 1089] A module of the present invention 1088 further includes a gas selection switch for selecting from a plurality of gas sources to adjust the composition of gas components in a perfusion fluid. [Invention 1090] A module of the present invention 1084, wherein the first interface includes a pulmonary artery cannula. [Invention 1091] A module of the present invention 1090, wherein the pulmonary artery cannula includes an insertion tube for insertion into the pulmonary artery, a connector portion connected to the insertion tube, and a main tube portion connected to the connector portion for connection to a circuit for transporting the flow of perfusion fluid to the lungs. [Invention 1092] The module of the present invention 1091 further includes a pressure transducer connector that defines an opening to a lumen of the connector portion near the insertion tube in order to position the pressure transducer near the point of inflow of perfusion fluid into the lungs. [Invention 1093] A module of the present invention 1092, wherein the pressure transducer connector provides an additional channel so that the pressure transducer can be remotely vented. [Invention 1094] A module of the present invention 1092, comprising a pulmonary artery cannula with two insertion tubes. [Invention 1095] A module according to the present invention 1092, wherein the insertion tube is separated from the main axis of the pulmonary artery cannula at an angle of approximately 15° to 90°. [Invention 1096] A module of the present invention 1067 in which the left atrial cuff of the lung is exposed to the lung chamber assembly in order to allow perfusion fluid to flow from the lung to the drain system. [Invention 1097] The module of the present invention 1067 further includes a disposable module which comprises a connection between a left atrial cuff and a cannula that directs perfusion fluid from the lung to a drain system. [Invention 1098] A lung chamber assembly module of the present invention 1067, comprising a housing, a support surface, and an openable / closable lid. [Invention 1099] The module of the present invention 1098, wherein the support surface defines drain and drainage channels for discharging perfusion fluid flowing from the lungs. [Invention 1100] The module of the present invention 1098, wherein the support surface is configured to fix a flexible wrap to provide support to the lung and anchor the lung. [Invention 1101] A module of the present invention 1098, wherein the flexible wrap contains polyurethane. [Invention 1102] A housing having a bottom surface including at least one housing drain, and walls; A support surface for supporting the lung, comprising a drain for draining perfusion fluid from the lung, and a support surface defining a drainage channel leading to the drain; With an openable lid that provides a sealable connection to the wall of the housing; A first interface to enable the flow of perfusion fluid to the lungs; A second interface to enable lung ventilation; A third interface to enable the flow of perfusion fluid away from the lungs and A lung chamber assembly, including the lung chamber assembly. [Invention 1103] An assembly of the present invention 1102, comprising a drain system for transporting a flow of perfusion fluid away from the lungs, the drain system including a measuring drain for directing a portion of the perfusion fluid flow to a sensor for perfusion fluid gas content, and a main drain for receiving the remainder of the perfusion fluid flow. [Invention 1104] The assembly of the present invention 1103, wherein the drain system further includes a region for collecting the flow of perfusion fluid away from the lungs into a pool that supplies it to a measuring drain, the measuring drain having a drainage capacity less than the flow rate of perfusion fluid away from the lungs. [Invention 1105] An assembly of the present invention 1104, wherein the flow of perfusic fluid overflowing from the aforementioned region flows to a main drain. [Invention 1106] The assembly of the present invention 1103, wherein the drain system further includes a wall that partially surrounds a measuring drain, partially blocking the flow of perfusion fluid from the measuring drain to the main drain, and promoting the formation of a pool of perfusion fluid above the measuring drain. [Invention 1107] An assembly of the present invention 1102, wherein the first interface includes a pulmonary artery cannula, the proximal portion of which is connected to a perfusion fluid circuit, and the distal portion of which is connected to the pulmonary artery of the lung. [Invention 1108] An assembly of the present invention 1107, wherein the wall of the housing defines an opening for the outer surface of a lung cannula to engage with the housing in a sealable manner. [Invention 1109] An assembly of the present invention 1107, further comprising a pulmonary artery cannula, which further includes a pressure transducer connector that defines an opening to the lumen of the cannula near the distal end of the cannula. [Invention 1110] An assembly of the present invention 1109, wherein the pressure transducer connector provides a channel so that the pressure transducer in the cannula can be remotely vented. [Invention 1111] An assembly of the present invention 1109, further comprising a pressure transducer located near the point of inflow of perfusion fluid into the pulmonary artery, and connected to an external controller by a pressure transducer connector and a pressure transducer cable passing through a pressure transducer conduit. [Invention 1112] An assembly of the present invention 1111, wherein the wall of the housing defines an opening for sealingly engaging with the outer surface of a pressure transducer conduit. [Invention 1113] The assembly of the present invention 1102, wherein the second interface includes a tracheal cannula having a distal insertion portion for insertion into the trachea, a proximal connector portion for connecting to a gas circuit for ventilating the lungs, and a locking mechanism adjacent to the connector portion. [Invention 1114] An assembly of the present invention 1113, wherein the wall of the housing defines an opening for a tracheal cannula locking mechanism to be sealedly engaged with the housing. [Invention 1115] An assembly of the present invention 1113, wherein the tracheal insertion section has a diameter of approximately 0.65 inches to 0.95 inches. [Invention 1116] The assembly of the present invention 1113, wherein the insertion portion is in contact with a rib having a diameter approximately 0.2 larger than the diameter of the insertion portion at its distal and proximal ends. [Invention 1117] The assembly of the present invention 1102, wherein the third interface includes a left atrial cuff exposed to the lung chamber assembly to allow perfusion fluid to flow from the lung to a support surface drain. [Invention 1118] The assembly of the present invention 1102 includes a third interface, which is a connection between the left atrial cuff and the cannula. [Invention 1119] An assembly of the present invention 1118, wherein the cannula is in fluid communication with a conduit that directs the perfusion fluid to a perfusion gas content sensor and a reservoir. [Invention 1120] An assembly of the present invention 1118, wherein the cannula directs the perfusion fluid toward a support surface drain. [Invention 1121] An assembly of the present invention 1118, wherein the cannula has a cage-like structure for achieving a small contact area between the cannula and the left atrial cuff. [Invention 1122] An assembly of the present invention 1017, wherein the cannula is configured to hold the left atrial cuff open. [Invention 1123] An assembly of the present invention 1017, further comprising a lumen and connectors for connecting the cannula to a pressure transducer positioned within the cannula. [Invention 1124] The stage of circulating perfusion fluid to the lungs, which enters the lungs through the pulmonary artery interface and leaves the lungs through the left atrial interface; The stage of ventilating the lungs through the tracheal interface by flowing a captive volume of ventilation gas back and forth between the lungs and a variable volume chamber; and This step involves introducing a further flow of ventilation gas into the collection chamber and allowing excess ventilation gas to pass through the collection chamber, thereby maintaining a predetermined composition of the ventilation gas and the minimum gas pressure of the collection chamber. Methods of preserving the lungs ex vivo, including. [Invention 1125] The method of the present invention 1124, wherein the ventilation gas comprises a composition of oxygen, carbon dioxide, and an inert gas. [Invention 1126] The method of the present invention 1125, wherein the inert gas is nitrogen. [Invention 1127] The method of the present invention 1124, wherein the gas content of the perfusion fluid reaches an equilibrium level corresponding to a predetermined composition of the ventilation gas. [Invention 1128] The method of the present invention 1124, wherein the ventilation gas has a predetermined composition containing about 5-20% oxygen and about 2-10% carbon dioxide. [Invention 1129] The method of the present invention 1128, wherein the gas content of the perfusion fluid reaches an equilibrium level having a hemoglobin saturation level of approximately 88% to 98%. [Invention 1130] The method of the present invention 1124, wherein the ventilation gas has a predetermined composition containing about 12% oxygen and about 5.5% carbon dioxide. [Invention 1131] The method of the present invention 1127, wherein the hemoglobin saturation level of the perfusion fluid entering the lungs reaches an equilibrium level of approximately 90-95%, and the hemoglobin saturation level of the perfusion fluid leaving the lungs also reaches an equilibrium level of approximately 90-95%. [Invention 1132] The method of the present invention 1124, wherein the oxygen content of the perfusion fluid entering the lungs is lower than physiological levels, and the oxygen content of the perfusion fluid leaving the lungs is higher than physiological levels. [Invention 1133] The method of the present invention 1124, wherein the further flow of ventilation gas is approximately 400-600 mL per minute. [Invention 1134] The method of the present invention 1124, wherein the amount collected is approximately 400 to 1200 mL. [Invention 1135] The method of the present invention 1124, wherein the minimum gas pressure for collection is approximately 4-8 cm for H2O. [Invention 1136] The method of the present invention 1124, wherein the maximum pressure of the ventilation gas is approximately 12-22 cmH of H2O. [Invention 1137] The method of the present invention 1124, wherein excess ventilation gas is passed through a relief valve that communicates with the collection volume. [Invention 1138] The method of the present invention 1124, wherein the variable volume chamber includes a bellows. [Invention 1139] The method of the present invention 1138, further comprising the step of compressing a bellows to induce a flow of ventilation gas to the lungs. [Invention 1140] The method of the present invention 1139, wherein the amount of ventilation gas flowing between the bellows and the lungs is determined by the size of the compression stroke of the bellows. [Invention 1141] The method of the present invention 1124, wherein the flow of ventilation gas from the lungs is caused by the contraction of the lungs. [Invention 1142] The method of the present invention 1124, wherein the pulmonary artery interface includes a pulmonary artery cannula, and a portion of the pulmonary artery cannula is inserted into the pulmonary artery of the lung. [Invention 1143] The method of the present invention 1124, wherein the perfusion fluid flows away from the lungs through the exposed left atrial cuff. [Invention 1144] The method of the present invention 1124, wherein the left atrial interface includes a sealed connection between the left atrium of the lung and a left atrial cannula. [Invention 1145] The method of the present invention 1124, wherein the tracheal interface includes a tracheal cannula, and a portion of the tracheal cannula is inserted into the trachea of ​​the lung. [Invention 1146] The method of the present invention 1124, wherein the perfusion fluid is maintained at a temperature close to physiological temperature. [Invention 1147] The method of the present invention 1124, further comprising the step of measuring a first level of oxygen content in the perfusion fluid flowing into the lungs and a second level of oxygen content in the perfusion fluid flowing out of the lungs. [Invention 1148] The method of the present invention 1124, further comprising the step of measuring at least one of the oxygen saturation level of hemoglobin in the perfusion fluid and the partial pressure of oxygen in the perfusion fluid flowing into the lungs. [Invention 1149] The method of the present invention 1124, further comprising the step of measuring at least one of the oxygen saturation level of hemoglobin in the perfusion fluid and the partial pressure of oxygen in the perfusion fluid flowing out of the lungs. [Invention 1150] The method of the present invention 1124, wherein the perfusion fluid contains a blood product. [Invention 1151] The method of the present invention 1150, wherein leukocytes are at least partially depleted in the perfusion fluid. [Invention 1152] The method of the present invention 1151, wherein platelets are at least partially depleted in the perfusion fluid. [Invention 1153] The method of the present invention 1124, wherein the perfusion fluid contains whole blood. [Invention 1154] The method of the present invention 1124, further comprising the step of delivering one or more therapeutic agents to the lungs during perfusion. [Invention 1155] The method of the present invention 1154, wherein one or more therapeutic agents are selected from antibacterial agents, vasodilators, and anti-inflammatory agents. [Invention 1156] The method of the present invention 1154, wherein one or more therapeutic agents are selected from the group consisting of prostaglandins, prostacyclins, dextran, isuprel, floran, and nitric oxide donors. [Invention 1157] The method of the present invention 1154, wherein one or more therapeutic agents are delivered through a tracheal interface via one of a sprayer and a bronchoscope. [Invention 1158] The method of the present invention 1124 further comprises the step of establishing a desired level of oxygen content in the perfusion fluid before initiating pulmonary perfusion. [Invention 1159] The method of the present invention 1158, wherein a desired level of oxygen content in the perfusion fluid corresponds to a hemoglobin saturation level of approximately 88% to 98%. [Invention 1160] The stage of circulating perfusion fluid to the lungs, which enters the lungs through the pulmonary artery interface and leaves the lungs through the left atrial interface; The stage in which the lungs are ventilated through the tracheal interface by flowing a collection volume of ventilation gas back and forth between the lungs and a variable volume chamber; This includes a step of introducing a further amount of ventilation gas into the collection volume and allowing excess ventilation gas to pass through the collection volume to maintain a predetermined composition of the ventilation gas and maintain the minimum gas pressure of the collection volume, The gas exchange within the lungs between the components of the ventilation gas and the perfusion fluid causes the corresponding gas components in the perfusion fluid to reach equilibrium. How to preserve the lungs with ex vivo. [Invention 1161] The method of the present invention 1160, wherein the ventilation gas is composed of at least one of oxygen and carbon dioxide. [Invention 1162] A perfusion fluid circuit for circulating perfusion fluid to the lungs, which enters the lungs through the pulmonary artery interface and leaves the lungs through the left atrial interface; A ventilation circuit for ventilating the lungs through a tracheal interface, the ventilation circuit being adapted to circulate a collection volume of ventilation gas back and forth between the lungs and a variable volume chamber; A trickle valve connected to the ventilation circuit and fluid to introduce a further amount of ventilation gas into the collection area; It includes a relief valve in fluid communication with a ventilation circuit to allow excess ventilation gas to pass through from the collection volume and to maintain the minimum gas pressure of the collection volume, Gas exchange within the lungs between the components of the ventilation gas and the perfusion fluid causes the corresponding gas components in the perfusion fluid to reach equilibrium. A system for preserving the lungs using ex vivo technology. [Invention 1163] A means for circulating perfusion fluid to the lungs, which enters the lungs through the pulmonary artery interface and leaves the lungs through the left atrial interface; A means for ventilating the lungs through a tracheal interface, wherein the ventilation circuit is adapted to circulate a collection volume of ventilation gas back and forth between the lungs and a variable volume chamber; Means for introducing a further amount of ventilation gas into the collection area; The system includes means for allowing excess ventilation gas to pass through from the collection volume and for maintaining the minimum gas pressure of the collection volume. Gas exchange within the lungs between the components of the ventilation gas and the perfusion fluid causes the corresponding gas components in the perfusion fluid to reach equilibrium. A system for preserving the lungs using ex vivo technology. [Invention 1164] The stage of circulating perfusion fluid to the lungs, which enters the lungs through the pulmonary artery interface and leaves the lungs through the left atrial interface; The stage of ventilating the lungs by delivering ventilation gas through the tracheal interface; A step of deoxygenating the perfusion fluid until the oxygen content in the perfusion fluid reaches a predetermined first value; and The process includes a step of re-oxygenating the perfusion fluid by ventilating the lungs with an oxygenated gas until the oxygen content in the perfusion fluid reaches a predetermined second value, The state of the lungs can be determined based on the time it takes for the lungs to change the oxygen content in the perfusion fluid from a first value to a second value. Methods for diagnosing lung conditions. [Invention 1165] The method of the present invention 1164, wherein the perfusion fluid is deoxygenated by ventilating the lungs with a deoxygenating gas containing CO2. [Invention 1166] The method of the present invention 1165, wherein the deoxygenated gas contains approximately 6% CO2. [Invention 1167] The method of the present invention 1164, wherein the perfusion fluid is deoxygenated by circulating the perfusion fluid through a gas exchange device, the gas exchange device is in fluid communication with a deoxygenated gas containing CO2 and N2, and oxygen is removed from the perfusion fluid by gas exchange between the deoxygenated gas and the perfusion fluid. [Invention 1168] The method of the present invention 1167, wherein the deoxygenated gas contains about 6% CO2 and about 94% N2. [Invention 1169] The method of the present invention 1164, wherein the perfusion fluid is deoxygenated by ventilating the lungs with a deoxygenating gas containing CO2 and N2. [Invention 1170] The method of the present invention 1164, wherein the perfusion fluid contains red blood cells, and a predetermined first value of the oxygen content in the perfusion fluid corresponds to approximately 73% saturation of the red blood cells. [Invention 1171] The method of the present invention 1164, wherein the perfusion fluid contains red blood cells, and a predetermined second value of the oxygen content in the perfusion fluid corresponds to approximately 93% saturation of the red blood cells. [Invention 1172] The method of the present invention 1164, wherein the oxygenating gas is air. [Invention 1173] The method of the present invention 1164, wherein the oxygenated gas contains approximately 25% to 100% oxygen. [Invention 1174] The method of the present invention 1164, wherein the perfusion fluid flows through the perfusion circuit at a rate of approximately 1.5 liters per minute. [Invention 1175] A method according to the present invention 1164 for diagnosing the lung while it is in transit. [Invention 1176] The method of the present invention 1164, wherein the perfusion fluid is maintained at a temperature close to physiological temperature. [Invention 1177] The method of the present invention 1164, wherein the perfusion fluid contains a blood product. [Invention 1178] The method of the present invention 1177, wherein the leukocytes are at least partially depleted in the perfusion fluid. [Invention 1179] The method of the present invention 1177, wherein platelets are at least partially depleted in the perfusion fluid. [Invention 1180] The method of the present invention 1164, wherein the perfusion fluid contains whole blood. [Invention 1181] The method of the present invention 1164, further comprising the step of delivering one or more therapeutic agents to the lungs during perfusion. [Invention 1182] The method of the present invention 1181, wherein one or more therapeutic agents are selected from antibacterial agents, vasodilators, and anti-inflammatory agents. [Invention 1183] The method of the present invention 1181, wherein one or more therapeutic agents are selected from the group consisting of prostaglandins, prostacyclins, dextran, isprel, floran, and nitric oxide donors. [Invention 1184] The method of the present invention 1181, wherein one or more therapeutic agents are delivered through a tracheal interface via one of a nebulizer and a bronchoscope. [Invention 1185] The method of the present invention 1164, further comprising the step of determining the time to reach first and second predetermined values ​​of oxygen content in the perfusion fluid by measuring the oxygen content of the perfusion fluid. [Invention 1186] The method of the present invention 1185, which measures the oxygen content of a perfusion fluid by determining the saturation level of red blood cells in the perfusion fluid using a pulse oximeter. [Invention 1187] An ex vivo perfusion circuit for circulating perfusion fluid to the lungs, which enters the lungs through the pulmonary artery interface and leaves the lungs through the left atrial interface; It includes a ventilation circuit for delivering ventilation gas to and from the lungs through a tracheal interface, The system is configured to deoxygenate the perfusion fluid until the oxygen content in the perfusion fluid reaches a predetermined first value, and to reoxygenate the perfusion fluid by ventilating the lungs with an oxygenated gas until the oxygen content in the perfusion fluid reaches a predetermined second value, and is further configured to determine the state of the lungs based on the time required for the lungs to change the oxygen content in the perfusion fluid from the first value to the second value. A system for diagnosing lung conditions. [Invention 1188] The system of the present invention 1187, configured to deoxygenate the perfusion fluid by ventilating the lungs with a deoxygenating gas containing CO2 and N2. [Invention 1188] The system of the present invention 1187, wherein the ventilation circuit further includes a gas exchange device, and the system is configured to deoxygenate the perfusion fluid by circulating the perfusion fluid to the gas exchange device while passing a deoxygenating gas containing CO2 and N2 through the gas exchange device, and the gas exchange device is adapted to remove oxygen from the perfusion fluid by gas exchange between the deoxygenating gas and the perfusion fluid. [Invention 1189] A means for circulating perfusion fluid to the lungs, which enters the lungs through the pulmonary artery interface and leaves the lungs through the left atrial interface; Includes means for delivering ventilation gas to and from the lungs through a tracheal interface, The system is configured to deoxygenate the perfusion fluid until the oxygen content in the perfusion fluid reaches a predetermined first value, and to reoxygenate the perfusion fluid by ventilating the lungs with an oxygenated gas until the oxygen content in the perfusion fluid reaches a predetermined second value, and is further configured to determine the state of the lungs based on the time required for the lungs to change the oxygen content in the perfusion fluid from the first value to the second value. A system for diagnosing lung conditions. [Invention 1190] An ex vivo perfusion circuit for circulating perfusion fluid to the lungs, which enters the lungs through the pulmonary artery interface and leaves the lungs through the left atrial interface; A ventilation circuit for delivering ventilation gas to and from the lungs through a tracheal interface. A lung care system including, Includes lung maintenance mode and lung diagnostic mode, The lung maintenance mode is configured to ventilate the lungs through the tracheal interface by flowing a collection volume of ventilation gas back and forth between the lungs and the variable volume chamber, and Diagnostic mode is: Deoxygenate the perfusion fluid until the oxygen content in the perfusion fluid reaches a predetermined first value; The perfusion fluid is re-oxygenated by ventilating the lungs with an oxygenated gas until the oxygen content in the perfusion fluid reaches a predetermined second value; and The system is configured to determine the state of the lungs based on the time it takes for the lungs to change the oxygen content in the perfusion fluid from a first value to a second value. Lung care system. [Invention 1191] The stage of positioning the lungs within the ex vivo perfusion circuit; The stage of circulating perfusion fluid to the lungs, which enters the lungs through the pulmonary artery interface and leaves the lungs through the pulmonary veins; The step of circulating the perfusion fluid to a gas exchanger that removes oxygen from the perfusion fluid; The stage of ventilating the lungs by delivering ventilation gas through the tracheal interface; A step in which, after the perfusion fluid has left the lungs, a first value of oxygen saturation in the perfusion fluid is measured at a point in the perfusion circuit; and The first stage of assessing lung condition based on the oxygen saturation level. Methods for diagnosing the lungs, including [specific example]. [Invention 1192] The method of the present invention 1191, wherein the step of determining the condition of the lungs includes determining the ratio between a first value of oxygen saturation and the fraction of inspired oxygen in the ventilation gas. [Invention 1193] A step of measuring a second value of oxygen saturation in the perfusion fluid at a point in the perfusion circuit near the pulmonary artery interface; and A stage in which the condition of the lungs is judged based on the difference between the first and second oxygen saturation values. The method of the present invention 1191, further comprising: [Invention 1194] The method of invention 1191, wherein the ventilation gas is air. [Invention 1195] The method of invention 1191, wherein the ventilation gas contains 25% to 100% oxygen. [Invention 1196] The method of the present invention 1191, wherein the perfusion fluid flows through the perfusion circuit at a rate of approximately 1.5 liters per minute. [Invention 1197] The stage of positioning the lungs within the ex vivo perfusion circuit; The stage of circulating perfusion fluid to the lungs, which enters the lungs through the pulmonary artery interface and leaves the lungs through the pulmonary veins; The stage of ventilating the lungs by delivering ventilation gas through the tracheal interface; A step of deoxygenating the perfusion fluid until the oxygen saturation level in the perfusion fluid reaches a predetermined first value; A step of re-oxygenating the perfusion fluid by ventilating the lungs with air until the oxygen saturation level in the perfusion fluid reaches a predetermined second value; and A step in determining the state of the lungs based on the time it takes for the lungs to change the oxygen saturation level in the perfusion fluid from a first oxygen saturation value to a second oxygen saturation value. Methods for diagnosing the lungs, including [specific example]. [Invention 1198] The method of the present invention 1197, wherein the perfusion fluid is deoxygenated by ventilating the lungs with a ventilation gas containing CO2 and N2. [Invention 1199] The method of Invention 1198, wherein the ventilation gas contains approximately 5.5% CO2 and 94.5% N2. [Invention 1200] The method of the present invention 1197, wherein the perfusion fluid is deoxygenated by circulating the perfusion fluid through a gas exchange device, the gas exchange device is in fluid communication with a ventilation gas containing CO2 and N2, and the oxygen composition in the perfusion fluid is adjusted by gas exchange between the ventilation gas and the perfusion fluid. [Invention 1201] The method of the present invention 1200, wherein the ventilation gas contains approximately 5.5% CO2 and 94.5% N2. [Invention 1202] The method of the present invention 1200, wherein a predetermined first value of oxygen saturation is approximately 77% oxygen. [Invention 1203] The method of the present invention 1200, wherein a predetermined second value of oxygen saturation is approximately 97%. [Invention 1204] Use of the lung care systems of the present invention 1001, 1032, 1063, 1162, 1163, 1187, 1189, or 1190 for ex vivo preservation or diagnosis of the lung. [Invention 1205] Use of the module of the present invention 1067 for ex vivo preservation or diagnosis of the lung. [Invention 1206] Use of the assembly of the present invention 1102 for ex vivo preservation or diagnosis of the lung. [Brief explanation of the drawing]

[0021] The following drawings illustrate exemplary embodiments of the present invention, where similar reference numerals indicate similar elements. These illustrated embodiments may not be drawn to scale and should be understood as illustrative, not limiting, representations of the present invention.

[0022] [Figure 1A] This is a schematic diagram of a described form of a portable organ care system. [Figure 1B] This is a schematic diagram of a described embodiment of a portable organ care system. It shows the gas-related components of the lung perfusion module. [Figure 2] This is a schematic diagram of the pulmonary perfusion circuit as described. [Figure 3] This is a schematic diagram of the gas loop of the organ care system in maintenance mode according to the described embodiment. [Figure 4] This is a schematic diagram of the gas loop of the organ care system in evaluation mode, relating to the described embodiment. [Figure 5]Figures 5A to 5B are schematic diagrams of the pneumatic circuit of a lung ventilation device according to the described embodiment. [Figure 6] This figure shows a typical pressure waveform in the lungs over the respiratory cycle, relating to the described embodiment. [Figure 7] Figures 7A to 7E show examples of tracheal cannulas relating to the described embodiment. [Figure 8] Figures 8A to 8F show examples of pulmonary artery cannulas relating to the described embodiment. [Figure 9] Figures 9A-9F show lateral views of the pulmonary artery cannula exemplified in Figures 8A-8F. [Figure 10] This is a diagram of the left atrial cannula. [Figure 11] This is a screenshot of the monitor for the organ care system in maintenance mode, relating to the described configuration. [Figure 12] This is a screenshot of the organ care system monitor in maintenance mode, showing the configuration menu maintenance tab related to the described configuration. [Figure 13] This is a screenshot of the monitor for the organ care system in continuous evaluation mode, relating to the described configuration. [Figure 14] These are screenshots of the organ care system monitor in sequential evaluation mode and deoxygenation sub-mode, relating to the described configuration. [Figure 15] This is a screenshot of the organ care system monitor showing the configuration menu for sequential evaluation submode settings related to the described configuration. [Figure 16] These are screenshots of the organ care system monitor in sequential evaluation mode and retention sub-mode, relating to the described configuration. [Figure 17] These are screenshots of the organ care system monitor in sequential evaluation mode and oxygenation sub-mode, relating to the described configuration. [Figure 18] This is a screenshot of the organ care system monitor showing the configuration menu for the evaluation tab related to the described configuration. [Figure 19]This is a screenshot of the organ care system monitor showing the configuration menu for ventilation device settings related to the described configuration. [Figure 20] This is a screenshot of the organ care system monitor showing the configuration menu for the lung tab related to the described configuration. [Figure 21] This is a screenshot of the organ care system monitor showing the configuration menu for the system tab related to the described configuration. [Figure 22] This is a diagram of the organ care system, drawn from a 45° angle to the front view, relating to the described configuration. [Figure 23] This is a side view of the organ care system relating to the described configuration. [Figure 24] This is a front view of the organ care system relating to the described embodiment. [Figure 25] This is a diagram of an organ care system with the side panels removed, relating to the described configuration. [Figure 26] This is a diagram of an organ care system in which the pulmonary perfusion module has been removed, relating to the described embodiment. [Figure 27] This is a diagram of a lung perfusion module relating to the described embodiment. [Figure 28] This is an exploded view of the lung chamber relating to the described embodiment. [Figure 29] This is a diagram of the lung support surface, housing, and front view of the lung chamber relating to the described embodiment. [Figure 30] This is a diagram showing the lung support surface, housing, and front view of a lung chamber, illustrating a tracheal cannula and a PA cannula according to the described embodiment. [Figure 31] This flowchart illustrates the steps taken at the lung donor site before the lungs are placed in the organ care system, relating to the described configuration. [Figure 32] This flowchart illustrates the steps taken during the transport of lungs from the donor site to the recipient site, relating to the described configuration. [Figure 33]This flowchart illustrates the steps taken at the lung recipient site to remove lungs from an organ care system and transplant them to a recipient, relating to the described embodiment. [Figure 34] This flowchart shows the steps involved in a continuous ex vivo assessment of the lungs. [Figure 35] This flowchart shows the steps involved in sequential lung evaluation using ex vivo therapy. [Modes for carrying out the invention]

[0023] Detailed explanation As previously stated in the summary, the embodiments described generally provide an improved approach to ex vivo lung care, particularly in ex vivo portable settings. The lung care system maintains the lungs in equilibrium by circulating a perfusion fluid through the pulmonary vascular system while rebreathing a specially formulated gas containing approximately half the oxygen of air into the lungs. The perfusion fluid circulates in the pulmonary artery (PA) via a cannula inserted into the PA. After passing through the lungs, the perfusion fluid exits the lungs through the open, cannula-free left atrium (LA), where it is drained into a reservoir. A pump removes the fluid from the reservoir, passes it through a heater and gas exchanger, and returns it to the cannula-inserted PA. In the embodiments described, the perfusion fluid is derived from donor blood. In alternative embodiments, the perfusion fluid is based on blood products, synthetic blood substitutes, a mixture of blood products and blood substitutes, or blood from a blood bank.

[0024] The described embodiments allow for prolonged ex vivo maintenance of the lungs, for example, 3 to 24 hours or longer. Such long ex vivo maintenance times expand the pool of potential recipients for the donor's lungs, reducing the importance of geographical distance between donors and recipients. Furthermore, long ex vivo maintenance times provide the necessary time for better genetic and HLA matching between the donor organ and the organ recipient, increasing the likelihood of a favorable prognosis. The ability to maintain the organ in near-physiological functional conditions also allows clinicians to diagnose organ function ex vivo and identify damaged organs. This is particularly useful in the case of lungs, as they are often impaired as a direct or indirect consequence of the donor's death. Therefore, even newly recovered lungs may be damaged. The ability to perform a rapid assessment of the recovered organ allows surgeons to determine the quality of the lungs and, if damaged, the nature of the problem. The surgeon then makes a decision on whether to discard the lung or apply treatment to it. Treatment options include the recruitment process, removal or stapling of damaged areas of the lung, aspiration of secretions, cauterization of bleeding blood vessels, and administration of radiation therapy. The ability to evaluate the lung at several stages from retrieval to transplantation and, if necessary, treat the lung significantly improves the overall chances of lung transplant success. In some cases, improved evaluation capabilities and longer maintenance times allow medical surgeons to perform physical repairs on donor organs with micro-defects. Increased ex vivo organ retention times also allow organs to be removed from the patient, treated in ex vivo isolation, and then returned to the patient's body. Such treatments may include, but are not limited to, pharmaceutical, gas, surgical, chemotherapy, biotherapy, gene therapy, and / or radiation therapy.

[0025] The lung care system will be described in the following order: First, an overview of the components of an exemplary organ care system will be provided. Second, exemplary operation of the system will be discussed, including lung preparation and its attachment to the system. Third, the use of the system for maintaining the lungs will be described. Next, two methods for evaluating the lungs, namely the continuous evaluation mode and the sequential evaluation mode, will be described in Sections 4 and 5. Sixth, the function of the lung ventilation pneumatic circuit will be described. Seventh, the user interface and system display of a typical organ care system during lung maintenance and evaluation will be shown. Eighth, exemplary implementation of the organ care system and its selected components will be described. Section 9 will describe an exemplary model for using the organ care system.

[0026] Overview of the Organ Care System Figure 1 is a block diagram showing the main components of the organ care system (OCS) 1000 adapted for lung preservation and treatment. The organ care system includes the OCS lung console 101, which is a permanent, multi-purpose, non-disposable component, and the lung perfusion module 400, which is a single-purpose, disposable component that comes into direct contact with the physical lung and the gases and fluids passing through it. The multi-purpose OCS lung console 101 includes four components: the OCS console 100; the lung console module 200; the OCS monitor 300; and probes (114) for measuring flow and probes (116, 118) for measuring oxygen and hematocrit levels in the perfusion fluid. In the embodiments described, the OCS 1000 is a self-contained, portable and portable unit that can be easily handled by one person for flat-plane transport using wheels, or easily lifted by two people when loading it into a vehicle, for example. When loaded with organs and perfusion fluid, the weight of the OCS 1000 is approximately 75 to 100 pounds, preferably about 80 pounds.

[0027] The OCS console 100 provides the system with processing, temperature, and power control services. During the manufacturing process, the OCS console 100 is adapted for use with the OCS lung console module 200. Alternatively, the OCS console 100 can be adapted for use with modules adapted to preserve organs other than the lungs, such as the heart, liver, or kidneys. The OCS console 100 includes a main processor 102, which is a Freescale MX1 in the described embodiment, that provides system control and process data. The main processor 102 distributes software to other processors in the system, including the lung console module controller 202, the heater controller 104, the OCS monitor processor 302, and the pump controller (not shown). It also manages data such as data received from the flow sensor 114, the pressure sensor 115, and the oxygen sensors 116, 118.

[0028] In the embodiments described, a heater controller 104, which is a PIC microcontroller, controls the heating of the perfusion fluid. A pressure transducer 223 measures the pressure of the internal maintenance gas in tank 221, thereby determining the amount of residual gas. A regulator 222 converts the gas tank pressure to 25 mmHg for use in the system. The internal maintenance gas tank 221 contains a mixture designed to provide sufficient oxygen to maintain lung tissue during the maintenance modes described below. In the embodiments described, the maintenance gas is composed of 12% oxygen, 5.5% carbon dioxide, and 82.5% nitrogen. In some embodiments, the OCS console 100 also includes an internal deoxygenation gas tank, a regulator, and a pressure transducer (not shown) for use during lung evaluation. The evaluation modes are described in a later section.

[0029] Functions specific to the preservation of the lungs (rather than other organs) are controlled by the lung console module 200. The lung console module 200 is connected to the OCS console 100 by data, power, and gas connections. The data connection links the main processor 102 on the OCS console 100 to the lung console module controller 202, which in the described embodiment is integrated on a PIC microcontroller. The power connection links the power control module 106 of the OCS console to a power converter 218, which in turn supplies power to the power-type components within the lung console module 200 at the appropriate voltage. The gas connection extends from the maintenance gas regulator 222 to a gas selector switch 216, which selects whether maintenance gas or deoxygenation gas flows to the lungs. In the described embodiment, the deoxygenation gas tank 501 is located outside the OCS 100, and the maintenance gas tank 221 is located inside the OCS console 100. In an alternative embodiment, the OCS console 100 also includes an internal deoxygenation gas tank. In another alternative embodiment, an additional external maintenance gas tank 221 complements the internal maintenance gas tank within the OCS console. The external gas tank can be supplied at the donor site, recipient site, or loaded onto a vehicle transporting the lungs. The external tank can be larger because it does not need to fit within the constrained volume of the OCS lung console 101, and can complement the limited gas supply source of the smaller internal gas tank of the OCS 1000.

[0030] The controller 202 manages the release of maintenance and evaluation gases by controlling valves, gas selector switches 216, and ventilators 214, thereby performing lung preservation in maintenance mode or lung evaluation in one of the evaluation modes. The blood gas solenoid valve 204 controls the amount of gas flowing into the blood gas exchanger 402. The airway pressure sensor 206 samples the airway pressure of the lung 404, detected through the isolation membrane 408. The relief valve actuator 207 is pneumatically controlled and controls the relief valve 412. Pneumatic control is performed by inflating or deflating an orifice throttling that blocks or unblocks the controlled air passage. This control method allows for complete isolation between the control system in the lung console module 200 and the ventilation gas loop in the lung perfusion module 400. Pneumatic control 208 controls the relief valve 207 and the bellows valve actuator 210. The pneumatic control circuit of the lung console module 200 is described in detail below. The trickle valve 212 controls the delivery of gas from the lungs 404 to the airways. The ventilator 214 is a mechanical device having actuator arms that contract and expand the bellows 418, which causes the inhalation and exhalation of gas into and from the lungs 404.

[0031] The OCS monitor 300 provides user control of the OCS 1000 via buttons and displays data from system sensors indicating the state of the lungs and the status of various subsystems within the OCS 1000. The monitor 300 is general-purpose, meaning it can be used for any organ. It includes a monitor processor 302 that runs software to control the monitor 300 and displays data on the LCD 304. In the embodiments described, the monitor processor 302 is a Freescale MX1. Examples of various screen displays are described below in relation to the usage modes of the OCS 1000. The OCS monitor 300 includes four control buttons for the user: a menu button 306 to launch the configuration menu, an alarm button 308 to mute the speaker, a pump button 310 to control the circulating pump, and an operation button 312 to provide access to certain organ-specific operations, such as ventilation control, or system operations, such as saving session files to an external memory card. Other controls may also be included, such as knobs for controlling values ​​or selecting items.

[0032] The OCS lung console 101 includes probes for measuring the properties of the circulating perfusion medium 250, also referred to herein as perfusion fluid and perfusion liquid. A flow probe 114 measures the flow rate of the perfusion fluid 250 through the system. In the embodiments described, the flow probe 114 is positioned on the perfusion liquid line leading to the pulmonary artery. A pressure sensor 115 measures the pulmonary artery pressure at the point of inflow of the perfusion fluid 250 into the lungs. Two oxygen saturation sensors 116 and 118 detect the amount of oxygen in the perfusion fluid 250 on the arterial side of the circuit, i.e., the oxygenated side, and on the venous side of the circuit, i.e., the deoxygenated side.

[0033] The pulmonary perfusion module 400 is in direct contact with the gas and fluid circuits flowing through the lung 404. Therefore, it is necessary to isolate it from the rest of the OCS 1000 so that tissues or fluids in contact with the organ do not come into contact with the OCS lung console 101. This is achieved by connecting it to the OCS lung console 101 via only a unidirectional gas line, or via an isolated control gas for pneumatic control, or by a mechanical actuator (for bellows). The entire pulmonary perfusion module 400, including all tissue and blood-contacting surfaces in the entire system, is disposable and replaced with each new lung placed in the OCS 1000. All tissue and blood-contacting surfaces are part of the disposable pulmonary perfusion module 400, which is manufactured from injection-molded components using inexpensive, biocompatible materials that are easily sterilizable. The pulmonary perfusion module 400 is shaped and sized for connection with the OCS console 100. The connection between the pulmonary perfusion module and the OCS console may include an interlocking mechanism or other mechanism for securing the perfusion module to the OCS console or otherwise maintaining the perfusion module in a desired position relative to the OCS console. In the embodiments described, the pulmonary perfusion module is easily attached to and removed from the OCS console 100 by a mechanical hinge and latch mechanism, as described below in reference to Figure 22. It is also connected by plug-in electrical and optical connections.

[0034] The pulmonary perfusion module 400 includes a bellows 418 actuated by a ventilator 214. The ventilator 214 uses a mechanical actuator arm to compress and release the bellows 418. By compressing the bellows, the lungs 404 inhale gas, and by releasing the bellows, it expands, and the lungs exhale gas. The distance the mechanical actuator travels when compressing the bellows 418 determines the tidal volume, i.e., the amount of gas inhaled by the lungs 404. The gas flowing into and out of the lungs passes through a gas filter 410, which prevents any fluid produced by the lungs from entering the gas loop.

[0035] To ensure gas isolation within the ventilation loop of the pulmonary perfusion module 400, all lung gas connections between the pulmonary perfusion module 400 and the OCS lung console 101 include a membrane to prevent gas from flowing back into and out of the OCS lung module 101. For example, pneumatically controlled gas connections from the relief valve actuator 207 and bellows valve actuator do not require an isolation membrane, as this gas does not come into contact with organs. One-way gas flow valves that allow flow only to the pulmonary perfusion module are automatically isolated from gases in the ventilation loop. Examples of such valves include the trickle valve 212 and the blood gas solenoid valve 204. An airway pressure sensor 206 samples the gas line pressure via an isolation membrane 408 that prevents any gas exchange toward the OCS lung console 101 in the backward direction.

[0036] The perfusion module 400 includes a blood-gas exchanger 402, which includes a perfusion fluid / gas exchange membrane that allows for the injection of gas into the perfusion fluid flow. The perfusion fluid circulates through circuits 406 and 407 between the lungs 404 and the gas exchanger 402. The organ chamber supports the lungs 404 and also channels the perfusion fluid coming from the lungs and left atrium to facilitate accurate measurement of arterial oxygen content levels. A detailed description of the perfusion circuit and organ chamber is given below.

[0037] The perfusion module 400 includes a relief valve 412, which helps reduce the gas pressure in the ventilator gas loop by providing a controlled release of gas to the outside. A bellows valve 414 controls the gas flow to or from the lungs. A check valve 416 is a one-way valve that allows outside air to be drawn into the ventilator system. A bellows 418 expands and contracts. When the ventilator system is used in rebreathing mode, the bellows exchange a substantially constant amount of gas with the lungs as it expands and contracts.

[0038] Figure 2 shows a pulmonary perfusion circuit. The circuit is entirely housed within a pulmonary perfusion module, and all its components are disposable. The perfusion fluid 250 circulates within the perfusion circuit, passing through the various components of the pulmonary perfusion module before passing through the vascular system of the lungs 404. A pump 226 ensures that the perfusion fluid 250 flows throughout the pulmonary perfusion circuit. It receives the perfusion fluid 250 from the reservoir 224 and pumps the solution through a compliance chamber 228 to a heater 230. The compliance chamber 228 is a flexible section of tubing that helps to mitigate the pulsatileness of the pump 226. The heater 230 replaces the heat that the perfusion fluid 250 loses to the environment during fluid circulation. In the embodiments described, the heater maintains the perfusion fluid 250 at or near a physiological temperature of 30–37°C, preferably about 34°C. After passing through the heater 230, the perfusion fluid 250 flows to a gas exchanger 402. Similar to the lungs, the gas exchanger 402 allows gas exchange between the gas and the perfusion fluid 250 through a gas-permeable hollow fiber membrane. However, the gas exchanger has an effective gas exchange surface area of ​​approximately 1 square meter, which is only a small fraction of the 50-100 square meter effective exchange area of ​​the lungs. Therefore, the gas exchanger 402 has limited gas exchange capacity compared to the lungs. The blood gas solenoid valve 204 regulates the supply of gas to the gas exchanger 402. The composition of the gas supplied to the gas exchanger is determined by which mode the OCS is in, which will be described in detail below. For example, if the OCS 1000 is in sequential evaluation mode, the deoxygenation gas 500 is supplied to the gas exchanger during the deoxygenation phase of the sequential evaluation cycle. After passing through the gas exchanger 402, the perfusion fluid 250 passes through the flow probe 114, pressure probe 115, and perfusion fluid oxygen probe 116. The inventors refer to the reading from the oxygen probe 116 as SvO2. This is because, similar to venous blood oxygen, it measures the oxygen in the perfusion fluid 250 just before the perfusion fluid enters the lungs. The sampling / injection port 236 facilitates the removal of the sample or injection of a chemical just before the perfusion fluid 250 reaches the lungs. The perfusion solution then enters the lungs 404 through the pulmonary artery 232 into which the cannula is inserted.

[0039] A pulmonary artery (PA) cannula connects the perfusion circuit to the vascular system of the lung 404. Several representative configurations of a pulmonary artery (PA) cannula are shown in Figures 8A-8F. Referring to Figure 8A, a single PA cannula 802 has a single insertion tube 804 for insertion into a single PA and is used to insert the cannula into the PA at a point before the PA branches into two lungs. To connect the cannula to the pulmonary artery, the insertion tube 804 is inserted into the PA and the PA is secured to the tube by sutures. The insertion tube 804 of cannula 802 is connected to a connector 805, which helps to position the insertion tube 804 at an angle and position suitable for a distortion-free connection of the lung 404 to the pulmonary artery. The connector 805 is connected to a main tube 808, which is attached to the perfusion fluid circuit. Figure 9A is a side view of the PA cannula 802 showing the angle between the insertion tube 804 and the connection part 805, in the described embodiment, the angle is approximately 15° to 30°, preferably approximately 22.5°.

[0040] Referring to Figures 8B-8F, the double PA cannulas 810, 820, 830, 840, and 850 each have two insertion tubes 812, 814, 822, 824, 832, 834, 842, 844, and 852, 854, with each pair of tubes forming angles 30°, 45°, 60°, 75°, and 90° from the main axis of the cannula in cannulas 810, 820, 830, 840, and 850, respectively. Each tube has a diameter of approximately 0.5–0.72 inches at the rib and approximately 0.4–0.62 inches on the body of the insertion tube. The variety of angles allows the surgeon to select the cannula that best fits the anatomy of the donor's lung. Referring to Figure 8B, the pair of insertion tubes 812 and 814 are joined in a Y-shape at the connector 815. As is most clearly shown in Figure 9B, the connector 815 is angled with respect to the main tube 818, and the angle is chosen to facilitate the insertion of the insertion tubes 812 and 814 into the pulmonary arteries of the lungs 404. In the embodiments described, the angle is 15–30°, preferably about 22.5°. Referring to Figures 9C–9F, similar angles of 15–30°, preferably about 22.5°, are shown between the connectors 825, 835, 845, 855 and their corresponding main tubes 828, 838, 848, and 858. An alternative to having PA cannulas with branched ends that form angles separated by various pre-set angles is to have malleable PA cannulas that can be bent to conform to the angle of the donor's pulmonary vessels.

[0041] The materials used in the manufacture of PA cannulas are described here. In an exemplary embodiment of a single PA cannula 802, the insertion portion 804 has a polycarbonate tip, and the connector portion 805 and main tube portion 808 are made of urethane tubing. In an alternative embodiment, the insertion tube 804, connector portion 805 and main tube portion 808 are all made of a single piece of silicone with a hardness of 50 Shore A to 90 Shore A, preferably 80 Shore A hardness. Similarly, in double PA cannulas, the main tubes 818, 828, 838, 848, 858 and connector sections 815, 825, 835, 845, 855 of double PA cannulas 810, 820, 830, 840, and 850 can be made of urethane, while the insertion tubes 812, 814, 822, 824, 832, 834, 842, 844, 852, and 854 can be made of polycarbonate. In an alternative embodiment, the entire double-tube PA cannula, i.e., the double insertion tube, connector section, and main tube, is made from a single piece of 80 Shore A silicone. The advantage of construction in silicone is that it is soft enough to provide a good foothold for the pulmonary vessels that are sutured onto the cannula connector. Furthermore, the silicone can be easily cut to the required length at the time of attachment to the pulmonary PA. Furthermore, because silicone can be molded into complex shapes, it is possible to fabricate the entire cannula from a single piece. One-piece construction of the cannula eliminates the joints between separate cannula components. Joints can generate undesirable turbulence in the perfusion fluid, introduce impurities, or cause leakage at the joints between separate components. In addition, one-piece construction requires only the molding of a single piece, which reduces costs and increases the reliability of the cannula.

[0042] Each PA cannula connection also includes a connector for connecting the perfusion fluid pressure transducer 115. Referring again to Figures 8A–8F and 9A–9F, PA cannulas 802, 810, 820, 830, 840, and 850 include pressure transducer connectors 806, 816, 826, 836, 846, and 856, respectively. The connector helps to position the perfusion fluid pressure sensor precisely at the point of inflow into the lungs where the perfusion fluid flow slows down, so that the pressure reading is not distorted by Bernoulli flow pressure. The pressure transducer connector also provides a channel for remote ventilation at the pressure sensor 115, which helps to ensure the accuracy of the pressure reading.

[0043] After passing through the lungs, the perfusion fluid exits the lungs from the left atrium, and a portion of it is removed along with the lung during external transplantation from the donor. During lung transplantation to the recipient, the left atrial tissue serves as an attachment zone, so it is important to keep it as intact and healthy as possible. Therefore, in the described embodiment, the left atrial cuff is not cannulated, which allows the circulating perfusion fluid to drain from the open left atrium and left atrial cuff.

[0044] In an alternative embodiment, the left atrial cuff is cannula-inserted by a cage-like cannula 1002, as shown in Figure 10. In this embodiment, all LA vessels are positioned inside the cannula, and then excess LA tissue is wrapped around the cannula. The cage-like structure 1004 of the LA cannula 1002 is designed to keep the left atrium open without occluding any pulmonary veins, thus helping to reduce the risk of damaging the tissue health. Inside the cannula, the perfusion fluid flowing from the pulmonary veins is collected in a tube 1006 and supplied to a perfusion fluid reservoir. A connector 1008 provides a connection point to a pressure transducer, which is positioned inside the cannula 1002 and capable of measuring the perfusion fluid pressure.

[0045] Using an "overflow cup" technique that allows sampling of the newly discharged fluid before it mixes with other perfusion fluids in the reservoir, the perfusion fluid exiting the lungs is collected in a dual drain system. All flow from the lungs is directed to a smaller cup that supplies the measuring drain. The capacity of this drain is limited by the use of a small-diameter tube. The perfusion fluid from the lungs exits at a flow rate exceeding the capacity of the measuring drain. The excess blood overflows this smaller cup and is directed to the main drain and therefore to the reservoir pool. The measuring drain obtains an accurate reading of the intra-arterial oxygen level, called SaO2, by directing the bubble-free flow of the newly discharged perfusion fluid to a second oxygen probe 118. After passing through the second sampling / infusion port 234, the perfusion solution completes its cycle and returns to the reservoir 224. The dual drain system is only necessary in configurations where the left atrial cuff is not cannulated. However, if the left atrial cuff is cannulated, for example with the cage cannula described below, the dual drain system is not necessary. This is because the newly discharged, bubble-free perfusion fluid in the solid column exits through the left atrial cuff into which the cannula was inserted.

[0046] In the embodiments described, the perfusion fluid 250 is composed of donor blood supplemented with heparin, insulin, vitamins, and antibiotics. Dextran is used to adjust colloid osmotic pressure, hematocrit level, and pH.

[0047] The following sections describe how to use the OCS 1000 to preserve and evaluate the lungs. The preinstrumentation section describes the initial steps in preparing the OCS 1000 and the lungs before connecting them to the OCS. The maintenance mode section describes how to use the OCS to preserve the lungs. The evaluation mode section describes two methods for evaluating the lung condition: continuous mode and sequential mode.

[0048] Before installing the fixture After the lungs are removed from the donor, a tracheal cannula is inserted into the trachea to provide a means of connection between the gas circuit of the pulmonary perfusion module 400 and the lungs. Figures 7A–7E show a series of representative tracheal cannulas. Referring to Figure 7A, the cannula 700 includes a tracheal insertion section 704 to which the trachea is secured by a cable tie or other means. In the embodiments described, the insertion section 704 is approximately 0.8 inches long. The base material of the cannula 700 is preferably composed of polycarbonate or another rigid, injection-molded, biocompatible plastic such as acrylic, polyester, K resin, nylon, polyethylene, or polypropylene. The upper layer above the insertion section 704 is preferably composed of soft silicone rubber, and alternative materials for the upper layer are other soft, biocompatible extruded or molded materials such as polyurethane, thermoplastic elastomers, and other rubber materials. Adjacent to the tracheal attachment portion 704 is a flexible portion 706, which is preferably composed of polyurethane or one of the other biocompatible materials listed above as suitable for the upper layer of the insertion portion. The insertion portion 704 and its upper layer, as well as the flexible portion 706, are injection moldable, and the silicone upper layer is overlaid onto the base portion. In an alternative embodiment, the silicone upper layer is molded separately or extruded and stretched onto the base portion.

[0049] The end of the insert 704, which is inserted into the trachea, has a rib 703, which helps to secure the insert 704 in place at the insertion site within the trachea and is secured by a cable tie placed around the trachea. At the opposite end of the insert 704, a second rib 705, having a diameter approximately 0.2 inches larger than the diameter of the base material of the insert 704, acts as a stop for the silicone upper layer and a stop for the trachea. The posterior rib 705 is a barbed fitting for tubing, approximately 0.5 inches long and having an angled barb for holding a 0.5-inch diameter tube. On the base material facing the lung OCS lung chamber connector 710, there is a second barbed fitting for tubing, approximately 0.5 inches long and having an angled barb for holding a 0.5-inch diameter tube.

[0050] By clamping the flexible portion 706, airflow to and from the lung 404 can be blocked. For example, clamping of portion 706 is used to maintain static inflation of the lung 404 after exotransplantation and before connection to the gas circuit of the OCS. Static inflation helps prevent lung collapse and resulting damage to the alveoli. In static inflation, the lung inflates to a water pressure of approximately 20 centimeters. Then, the tracheostomy cannula clamp is released at the flexible portion 706.

[0051] Near the end of the flexible section 706, furthest from the tracheal inlet, the cannula 700 includes a lock nut 708 for securing the cannula to the lung chamber. The lock nut 708 is fitted onto the stepped section of the cannula tube. A 0.7-inch long 15mm connector 710 adjacent to the lock nut 708 helps connect the cannula to a standard ventilator connector, which connects the lung to the gas circuit of the OCS. The tracheal cannula is designed to fit the donor's lung, which has a tracheal diameter that varies according to the donor's size. Figure 7A shows a tracheal cannula 700 with an inlet tip diameter 702 of 0.9 inches. Figures 7B, 7C, 7D, and 7E show cannulas with insertion tip diameters of 0.85, 0.80, 0.75, and 0.70 inches for insertion sections 724, 744, 764, and 784, respectively. Cannulas with insertion diameters smaller than 0.7 inches or larger than 0.9 inches may be required to fit lungs from certain donors.

[0052] Before receiving the lungs, the OCS perfusion circuit is primed with donor blood, priming fluid, and medication. This perfusion fluid is then circulated and warmed. During this phase, the gas exchanger 402 establishes the blood gases corresponding to the maintenance mode. This is achieved by setting the gas selector switch 216 to allow the maintenance gases to flow into the gas exchanger, and by the load cycle adjusting the gas exchanger valve 204 to provide a low mean flow rate of maintenance gas through the gas exchanger. Gas exchange within the gas exchanger brings the circulating perfusion fluid to equilibrium with the maintenance gases, establishing the desired maintenance perfusion fluid gas levels of O2 and CO2. The pH of the perfusion fluid is controlled by the CO2 level. These preparatory steps ensure that the perfusion fluid has already reached the maintenance gas levels when the lungs are mounted onto the OCS, which helps to accelerate the transition of the lungs to the maintenance mode.

[0053] Maintenance mode The maintenance mode allows for the long-term preservation of lungs by placing them in safe and stable conditions. The maintenance gas satisfies the cellular requirements of lung cells by placing the lungs in equilibrium with a gas containing oxygen to meet their metabolic needs and carbon dioxide to control blood pH. Because the lungs consume less oxygen, each breath can be substantially reused, dramatically reducing the consumption of fresh gas. Since donated organs typically need to be transported to different locations where the recipient resides, reducing the amount of gas required to support the lungs, thereby increasing the system's portability, is a significant benefit.

[0054] When positioning the lungs within the organ chamber, connect the tracheal cannula to the system gas line in rest mode. In rest mode, the bellows 418 are fully expanded, i.e., ready for the first lung inhalation. Remove the clamp on the tracheal cannula and equalize the pressure in the lungs and gas line. Then begin inhalation.

[0055] Figure 3 shows the function of the OCS in maintenance mode. In maintenance mode, the ventilation system moves the collected gas back and forth between the lungs and the bellows to rebreathe the gas into the lungs. In addition, a small amount of maintenance gas 220 is gradually introduced into the ventilation circuit with each breath through valve 212. Excess gas is exhausted from the circuit through relief valve 412 to prevent pressure increases and maintain a desired minimum gas pressure in the system. In the embodiments described, the maintenance gas 220 is composed of about 9-15% oxygen, preferably about 12% oxygen, about 4-7% carbon dioxide, preferably about 5.5% carbon dioxide, and the remainder being nitrogen.

[0056] The composition of the maintenance gas 220 includes approximately half the amount of oxygen found in air, and an amount of carbon dioxide that maintains a near-physiological pH level in the perfusion fluid 250. In maintenance mode, equilibrium is achieved between the maintenance gas 220 and the perfusion fluid gas levels. At this equilibrium, there is only a small difference between the oxygen level in the perfusion fluid 250 entering the lungs 404, i.e., the venous level PvO2, and the level leaving the lungs 404, i.e., the arterial level PaO2. The composition of the maintenance gas 220 is chosen to achieve a perfusion fluid oxygen level that deviates as little as possible from the physiological blood gas levels. Too high an oxygen content results in a venous oxygen level significantly above the physiological level, while too low an oxygen level results in an arterial oxygen level significantly below the physiological level. A preferred maintenance gas composition is a compromise between these levels, achieving equilibrium arterial and venous oxygen levels in the perfusion fluid 250 that are approximately midway between the physiological venous and arterial levels. A favorable oxygen content of approximately 12% provides more than enough oxygen to meet the metabolic needs of the lungs. Furthermore, an oxygen level of 12% is close to the oxygen level in the alveoli of healthy lungs breathing air. This is because a gradient exists between the oxygen level in the trachea and the alveolar level caused by gas exchange along the airway pathways to the lungs. In lung 404 in maintenance mode, this gradient does not exist when the maintenance gas is rebreathed, and the oxygen level is approximately 12% throughout the lungs.

[0057] First, when connecting the lungs to the OCS gas line, fill the gas loop with air, not the maintenance gas. Therefore, lung ventilation is initially performed with air. As the ventilation gas is gradually introduced and excess gas is released, the composition of the gas in the gas loop will soon change to that of the maintenance gas.

[0058] In maintenance mode, the gas selector valve 216 (Figure 1) is set to select the maintenance gas tank 221. The gas exchanger valve 204 is always closed in maintenance mode because the gas exchanger 402 is not used. The bellows valve 414 is always open to maintain gas exchange between the bellows and the lungs. Referring to Figure 3, the passive check valve 416 brings air into the circuit under suction conditions, but remains closed during maintenance mode because the ventilation circuit always has positive pressure.

[0059] At the start of each maintenance mode cycle, the bellows 418 are in a fully open position, and the lungs are at their minimum volume. During this cycle, the bellows 418 are compressed, moving the gas to the lungs. The lungs expand to receive this amount of gas, increasing the pressure. Once the specified amount of gas has been delivered, the bellows 418 pause for a specified plateau time before initiating the exhalation phase of the cycle. During exhalation, the bellows 418 return to their initial fully expanded state, and the lungs relax. The next ventilation cycle begins after an interval set at a specified breathing rate. The degree to which the bellows 418 are compressed during the inhalation phase of each cycle is determined by the user-specified tidal volume, typically between 400 and 1200 mL.

[0060] Figure 6 shows a typical respiratory pressure waveform 650 in each ventilation cycle. At the start of the cycle, the pressure is set to a positive end-expiratory pressure (PEEP) value 652, which is approximately 5 cm of H2O. As the bellows are compressed in the inhalation section 654 of the cycle, the pressure increases to a peak pressure 656 and remains at the peak pressure in the plateau section 658 of the cycle. In the embodiments described, the peak pressure is approximately 20 cm of H2O. In the exhalation section 660 of the cycle, the pressure decreases until the desired PEEP level is reached at the end of the cycle. The duration 662 of a complete ventilation cycle is set by the breathing rate selected by the user and is typically about 6 seconds.

[0061] Two other events occur in each maintenance mode ventilation cycle. During the inhalation phase 654, the trickle valve 212 opens briefly to introduce a specified amount of calibration maintenance gas into the circuit. Then, at the end of the exhalation phase 660, the relief valve 412 opens briefly to exhaust excess gas to the outside air until the desired PEEP is reached. The openings of the trickle valve 212 and the relief valve 412 are indicated by traces 664 and 666, respectively, in Figure 6.

[0062] The average flow rate of maintenance gas into the ventilation loop is specified by the user and is typically 500 ml / min. At a ventilation rate of 10 breaths per minute, the trickle valve 212 delivers 50 ml of maintenance gas to the circuit in each cycle. When ventilating with a typical tidal volume of 600 ml, the amount of maintenance gas injected in each cycle is only about 10% of the tidal volume and therefore has little effect on any given ventilation cycle. The flow rate of maintenance gas is usually set to the minimum level necessary to keep the gas composition in the gas loop close to the maintenance gas level, despite the lung's metabolic tendency to decrease oxygen levels and increase CO2 levels. Maintenance gas injection is also used to maintain the desired PEEP level in the system. Gas leakage from the lungs and respiratory fittings also affects the amount of maintenance gas injected.

[0063] Because the lungs have low metabolic activity, they require very little oxygen for support and produce only small amounts of carbon dioxide. Therefore, the metabolism of the lungs themselves has little effect on the composition of the ventilation gas and perfusion fluid gas. Since the maintenance gas is injected into the gas line during each ventilation cycle, the composition of the ventilation gas and perfusion fluid gas quickly reaches the same composition, i.e., that of the maintenance gas. When this situation occurs, the lungs reach equilibrium with the maintenance gas. In equilibrium, the oxygen level in the perfusion fluid achieves a steady state value. The steady state level of SaO2 is in the range of approximately 93-95%, slightly lower than the physiological level. The corresponding steady state SvO2 level is in the range of approximately 90-91%, higher than the physiological level. Therefore, in maintenance mode, the difference between the saturation levels in the perfusion fluid throughout the lungs is smaller than the physiological difference. This higher SvO2 is partly due to the absence of the deoxygenation effect of body tissues that is present in the physiological case. These lower SaO2 levels are partly caused by ventilating the lungs with a maintenance gas that contains only about half the amount of oxygen as the air.

[0064] In improving maintenance mode ventilation, the system maintains accurate and constant tidal volume delivery to the lungs by shortening the bellows compression stroke, which corresponds to the amount of gas contributed by the trickle valve 212.

[0065] Evaluation mode - Continuous Figure 4 is a schematic diagram showing the various components involved in performing the lung assessment. In continuous mode assessment, the system mimics a bodily process by removing oxygen from the perfusion fluid after air is inhaled into the lungs and before the perfusion fluid returns to the lungs. In the body, oxygen removal is achieved by tissues, while in OCS, it is achieved by deoxygenated gases flowing through gas exchangers. Continuous mode assessment tests the gas exchange capacity of the lungs by measuring how well the lungs can deoxygenate the blood. This measurement is performed by measuring venous and arterial blood oxygen levels. Scoring of lung performance in continuous assessment mode will be discussed further below.

[0066] Figure 34 is a flowchart showing the main steps involved in performing a continuous assessment of the lungs. In step 3402, the deoxygenated gas flows into the gas exchanger 402. This is achieved by using a gas selector switch 216 set to select the deoxygenated gas 500 and opening the gas exchanger valve 204 to connect the gas exchanger 402 to the deoxygenated gas supply source. In the embodiment described, the maintenance gas consists of 4–7% CO2, preferably 6% CO2, and the remainder nitrogen. In this mode, the trickle valve 212 is kept closed. In step 3404, the lungs are ventilated with air or another ventilation gas using a bellows 418, which delivers fresh breath of air or other ventilation gas to the lungs between the inhalation phases of each cycle.

[0067] Figure 6 shows the gas pressure profile and valve settings in a continuous-mode ventilation cycle. At the start of the cycle, the bellows 418 is in the fully open position, the lungs are at their minimum volume, and the pressure is at the PEEP level 652. The bellows valve 414 is opened 668, and the bellows is compressed, moving the gas to the lungs during the inhalation phase 654. The lungs expand to accept the gas, and the pressure increases accordingly. Once the bellows 418 has delivered the specified amount of gas, the system pauses for a user-specified plateau time 658 (also called stagnation time) before starting the exhalation phase 660 of the cycle. During exhalation, the connection between the bellows and the lungs is sealed by closing the bellows valves 414, 670. On the lung side of the circuit, the relief valve 412 is opened 672 to exhaust gas from the lungs until the PEEP level is reached, at which point the relief valve 412 is closed 674. Simultaneously, the bellows 418 is expanded to the fully extended position. This creates suction on the bellows side, which is released by the passive check valve 416, which fills the bellows with outside air in preparation for the next inhalation cycle. The next ventilation cycle begins at a time determined by the user-specified breathing rate. In this way, the coordinated operation of the bellows valve 414 and the relief valve 412 during each cycle causes continuous ventilation of the lungs with fresh air.

[0068] In an alternative embodiment, the bellows valve 414 is closed at the end of the suction phase 654 prior to the plateau 658. This allows the bellows expansion to begin immediately after the suction phase.

[0069] Other gases can be supplied to the inlet of check valve 416. In fact, gases of any desired composition can be supplied. For example, gas can be supplied from a typical gas entrainment device that provides oxygen concentration in hospitals. Such a device can supply ventilation gas at standard oxygen levels of 50% or 100%.

[0070] The deoxygenated gas flows through the gas exchanger 402, and the lungs are ventilated with air, but as shown in Figure 34, step 3406, the perfusion fluid circulates through the lungs and the gas exchanger. To approximate physiological conditions while evaluating the lungs in continuous mode, it is desirable to supply the lungs with venous perfusion fluid having an oxygen level similar to that of the body. The gas exchanger 402 has limited gas exchange capacity, and at a physiological blood flow rate of 3-4 l / min, it is impossible to reduce the saturation level to a body-corresponding level by removing sufficient oxygen from the blood while circulating blood to the lungs, where reoxygenation occurs intermittently. Therefore, the flow rate is reduced to approximately 1.5 l / min to enable the gas exchanger 402 to achieve a physiological level of oxygen in the venous blood. In an alternative embodiment, an intermediate flow rate between 1.5 l / min and the physiological flow rate of 3-4 l / min is used, and venous blood with a correspondingly higher oxygen level enters the lungs. In the embodiments described, there is a trade-off between approximating physiological blood gas levels as blood enters the lungs and approximating physiological flow rates. This trade-off can be reduced or eliminated by increasing the gas exchange capacity of the system. One approach involves using multiple gas exchangers in series or parallel within the pulmonary perfusion circuit. Another approach involves increasing the gas exchange capacity of the gas exchangers by providing them with larger gas exchange surfaces.

[0071] Typically, a continuous mode assessment is performed immediately after the lungs have been kept in maintenance mode. The following alternative embodiments expedite the transition from maintenance mode to continuous mode assessment. Initially, in maintenance mode, the bellows 418 contains the entire volume of maintenance gas that would normally flow through several air ventilation cycles. Instead, a sweeping operation is performed to replace the entire contents of the bellows 418 with air. During this sweeping, the bellows valve 414 is opened, and the bellows 418 is compressed completely at a slow rate. During this compression, the relief valve 412 is actively controlled to maintain the pressure near the PEEP level. At the end of this compression cycle, the bellows valve 414 is closed, and the bellows 418 is fully expanded, filling its entire volume with fresh air from the check valve 416. One or more sweeping cycles can be performed to fully establish the new gas composition.

[0072] Once the system reaches a steady state, the oxygen level in the perfusion fluid entering and leaving the lungs is measured, as shown in Figure 34, step 3408. A perfusion fluid sample can also be taken to confirm the oxygen level and determine other components of the perfusion fluid. In continuous evaluation mode, the user assesses the lung's gas exchange capacity by determining how much oxygen the lungs can transfer to the perfusion fluid with each breath. This assessment is based on measured oxygen levels in the perfusion fluid entering and leaving the lungs (3410). This assessment is calibrated using various parameters, such as the oxygen fraction in the gas ventilating the lungs. A standard measure of gas exchange capacity is the ratio between the partial pressure of blood oxygen in millimeters of mercury (PaO2) and the fractional inspired oxygen value (FiO2). In a normal, resting individual, this ratio is 100 / .21 = 450. A ratio below 300 indicates impaired lung function, and a ratio below 200 indicates acute respiratory distress syndrome (ARDS). However, some standardization adjustments are necessary to make this measure effective as an evaluation tool within OCS. One important adjustment concerns the deoxygenation level (PvO2) of the blood before it enters the lungs. Generally, due to the limited deoxygenation capacity of the gas exchanger, the PvO2 level in OCS is higher than that in an individual. Therefore, given the gas exchange capacity of the lungs, a higher PaO2 is expected in the lungs in continuous evaluation mode of OCS than in vivo.

[0073] Another measure of the lung's gas exchange capacity is the difference between the oxygen level of blood entering the lungs (PvO2) and that of blood leaving the lungs (PaO2). In a normal individual, the PvO2 level is approximately 40 mmHg, the PaO2 is approximately 100 mmHg, and the difference between the incoming and outgoing oxygen levels is 60 mmHg. For OCS, the PvO2 level can be 60 mmHg, and a healthy lung can achieve a PaO2 of 115 mmHg, resulting in a PaO2-PvO2 value of 55 mmHg, which is close to the corresponding value in vivo.

[0074] To enable the measured continuous mode parameters as an evaluation tool, several standardization adjustments are necessary. These adjustments are based on factors such as ventilation parameters, hematocrit levels, blood flow, lung volume, altitude, and temperature.

[0075] Sequential evaluation mode The sequential evaluation mode is a second method for diagnosing the gas exchange capacity of the lungs. In this mode, the lungs are subjected to deep venous perfusion oxygen levels, which then subject the lungs to different capacity tests than those in the continuous evaluation mode.

[0076] Sequential assessment involves three phases: deoxygenation, retention, and reoxygenation. The deoxygenation phase removes oxygen from the total perfusion fluid in the system. Following the retention phase, the lungs reoxygenate the perfusion fluid pool. The rate at which the lungs achieve reoxygenation indicates their gas exchange capacity. Figure 35 shows the main steps involved in performing sequential assessment of the lungs.

[0077] The oxygen content of the perfusion fluid 250 is reduced using deoxygenation phases 3502 and 3504. This is achieved by using both the gas exchanger 402 and the lungs 404. To allow the gas exchanger 402 to deoxygenate the blood, the gas selector valve 216 is set to select the deoxygenation gas and the gas exchanger valve 204 is opened to supply it with the deoxygenation gas 500. The gas exchanger can deoxygenate the blood on its own, but the lungs and ventilator are used to accelerate the process. To achieve this, the ventilator is configured to operate as a rebreather as well as in maintenance mode (see above), and the trickle valve 212 injects the deoxygenation gas 500 into the gas circuit. Within several ventilator cycles, the rebreathed gas in the gas circuit matches the deoxygenation gas composition, i.e., approximately 6% CO2 and 94% N2, and the lungs work to deoxygenate the perfusion fluid circulating them. In effect, the lungs are used as a highly effective gas exchanger that helps deoxygenate the perfusion pool. As shown in Figure 35, step 3504, the deoxygenation phase continues until the oxygen in the perfusion comes within a user-defined threshold range, which is typically about 50-70% oxygen, preferably about 60% oxygen.

[0078] In the holding phase 3506, the deoxygenation process is interrupted by closing the gas exchanger valve 204 and the trickle valve 212 while the perfusion fluid continues to flow through the perfusion circuit. During this phase, the perfusion fluid pool is stabilized to a uniform deoxygenation level. The time required to achieve uniformity may depend on the flow rate of the perfusion fluid. In an alternative embodiment, the oxygen content levels in the arteries and veins are monitored, and the holding phase is maintained until these levels remain equivalent and constant for an extended period. During the holding phase, ventilation is interrupted, or the system prepares for the reoxygenation phase by performing one or more scavenging cycles (described earlier in the section on continuous evaluation). Scavenging cycles play a useful role here because they switch the gas in the gas circuit from the deoxygenation gas to its opposite, air, and because the gas circuit needs to be initially filled with air in order to immediately begin oxygenation of the perfusion fluid.

[0079] In the final phase of the sequential evaluation mode, the oxygen-depleted perfusion fluid pool is reoxygenated by ventilating the lungs with air or another ventilation gas (stage 3508). Ventilation is performed using the same method as described above for the continuous evaluation, with the difference that the gas exchange valve 204 is kept closed. Therefore, in the reoxygenation phase of the sequential evaluation mode, the lungs are the sole gas exchange source in the perfusion circuit (stage 3510). The time required for the lungs to reoxygenate the perfusion fluid pool is a primary indicator of the lung's gas exchange capacity. The measured reoxygenation time is the time it takes for the perfusion fluid 250 to move from a deoxygenated state to a predetermined oxygenation level, measured by one or both of the pulse oximeter probes 116 and 118 (stage 3512). In an alternative embodiment, a blood sample is taken from one or more of the sampling ports 234, 236, and the saturation level is measured by a laboratory blood gas analyzer. The degree of saturation at the oxygenation threshold level is set within the range of 90% to 100%, preferably set to 93%.

[0080] Lung gas exchange capacity, measured by the time it takes for air-ventilated lungs to reoxygenate blood from the deoxygenation threshold level to the oxygenation threshold level, provides a measure of lung health (stage 3514). Generally, healthy lungs can reoxygenate a perfusion pool in 4-5 breaths, which corresponds to a sequential assessment mode reoxygenation time in the range of 45-90 seconds, typically about 1 minute. Effective use of reoxygenation time as an assessment tool may require standardization based on ventilation parameters, hematocrit, blood flow, lung volume, and altitude.

[0081] In an alternative mode of evaluation, a gas other than air is supplied to the inlet of the check valve 416 during the oxygenation phase. For example, in a hospital setting, a gas from a device that provides gas at 50% or 100% oxygen can be used to supply the ventilation gas. In this case, the reoxygenation time is reduced, and the measurement of the reoxygenation time must be properly calibrated to determine the gas exchange capacity of the lungs.

[0082] Another method for evaluating the gas exchange capacity of the lungs during sequential evaluation mode is to measure the rate at which the lungs deoxygenate the perfusion fluid 250 during the deoxygenation phase. The effectiveness of the lungs in deoxygenating the perfusion fluid 250 while being ventilated with deoxygenated gas 500 provides an indicator of the lung's gas exchange capacity.

[0083] The advantage of the sequential evaluation mode is that, since gas exchange occurs solely by the lungs during reoxygenation, a physiological blood flow rate of 3-4 l / min can be used. Because no gas exchanger is involved, there is no need to restrict blood flow.

[0084] Lung ventilation system pneumatic circuit The lung ventilation system pneumatic circuit provides means for controlling bellows valves 414 and relief valves 412 to control various ventilation modes. It also controls the blood gas exchanger 402 and gas flow to the lungs. Pneumatic control offers several advantages, including the ability to open and close valves at different speeds, the availability of inexpensive, disposable pilot valves, the ability to isolate the lung console module 200 from gas-carrying valves exposed to the lungs, and providing a simple, modular interface for connecting and disconnecting disposable lung perfusion modules 400 to and from the console module 200.

[0085] The software running on the console module controller 202 controls the pneumatic control module 208, which in turn controls the relief valve actuator 207 and the bellows valve actuator 210. Figure 5a shows the components of the pneumatic circuit within the lung console module 200 and how the circuit is connected to the lung perfusion module 400. Components corresponding to the pneumatic control module 208 shown in Figure 1 are identified by dotted lines in Figure 5a. Table 1 is a list of pneumatic circuit components relating to the described embodiment.

[0086] [Table 1]

[0087] The pneumatic circuit of the lung console module 200 is connected to the lung perfusion module 400 via gas connectors 624 and 626. Figure 5b shows a front view of connector 624, which has a 6-lumen connector, and gas lines 630, 632, 634, 636 and 638 provide connections to the gas exchanger 402, the rebreathing gas circuit, the bellows valve 414, the relief valve 412, and the airway pressure, respectively. The connectors allow for the rapid removal and connection of the disposable lung perfusion module 400 to the lung console module 200.

[0088] The maintenance gas 220 and deoxygenation gas 500 are connected to the gas selector switch 216 by connectors 604 and 602, respectively. The gas selector switch 216 selects which gases to pass through the gas exchanger valve 204 and the trickle valve 212. The control of the trickle valve 212 is synchronized with the ventilation cycle, and this valve is opened during the suction phase as previously described in Figure 6, and is kept open for a sufficiently long time to obtain the desired average gas flow rate. The flow rate to the gas exchanger 402 is controlled by adjusting the pulse width of the control valve 204 from valve 216. Valves 204 and 212 perform gas flow rate control using orifice throttling 205 and 213, respectively.

[0089] Both the bellows valve 414 and the relief valve 412 are capable of high flow rates, such as 1 liter / second. In the case of the bellows valve 414, the high flow rate capacity allows for an unrestricted and free gas flow between the lungs and the bellows during inhalation and exhalation. In the case of the relief valve 412, the high flow rate capacity allows the lungs to exhale rapidly to the PEEP value. In the embodiments described, the bellows valve 414 and the relief valve 412 are commercially available high-flow pilot valves. The valve is closed by applying positive pressure to the pilot valve diaphragm, and negative pressure completely opens the valve.

[0090] The lower part of Figure 5a shows how pilot valve control is implemented for the bellows valve 414 and the relief valve 412. The constant movement of the air pump 612 provides a nearly constant airflow through the air pump. The pump draws in ambient air through the inlet filter 606 and check valve 608. This flow creates a pressure difference of approximately 1 PSI or 70 cm of H2O across the check valve 608, which results in an inlet reservoir 610 pressure of H2O -70 cm relative to the ambient air. The inlet reservoir 610 and outlet reservoir 614 serve to filter out non-uniform pressure fluctuations from the reciprocating pump 612. After passing through the outlet reservoir 614, the effluent from the air pump 612 flows through a second 1 PSI check valve 616. Thus, the pressure in the outlet reservoir 614 is 70 cm above the ambient pressure, assuming the relief valve actuator 207 is open to ambient pressure.

[0091] The bellows valve 414 is controlled as follows: The bellows valve actuator 210 can be connected to either the inlet reservoir 610 or the outlet reservoir 614. To open the bellows valve 414, the actuator 210 is connected to the inlet reservoir 610 at H2O -70cm. The actuator 210 transfers this negative pressure to the diaphragm of the bellows valve 414 via the pneumatic line 634. The negative pressure on the diaphragm opens the valve 414. To close the bellows valve 414, the actuator 210 is connected to the outlet reservoir 614 at H2O +70cm to apply positive pressure to the valve diaphragm and shut off the valve.

[0092] The relief valve 412 is controlled by applying positive pressure to the valve's diaphragm, in which case a controllable pilot gas pressure of the valve is used to set the PEEP in the perfusion module gas circuit. As long as the pressure in the ventilation loop is greater than the pilot pressure on the valve's diaphragm, the relief valve 412 remains open and the gas in the ventilation loop is vented to the outside. If the pressure in the ventilation loop is less than the pilot pressure, the relief valve 412 closes. Thus, by setting the pilot pressure to a desired PEEP value, the relief valve allows gas to vent from the gas loop until the pressure reaches the desired PEEP level, after which it is shut off. In an alternative embodiment, the PEEP valve is actuated at a higher or lower pilot pressure to generate its calling rate through the valve.

[0093] Variable control of the pilot pressure in the relief valve 412 is achieved by using a linear stepper motor 618 in combination with a variable orifice valve in the relief valve actuator 207. The stepper motor 618 controls the size of the opening of the variable orifice valve. As the orifice opening becomes smaller, the resistance to airflow increases, reducing the airflow from the air pump 612 to the ambient air and increasing the pressure between the check valve 616 and the relief valve actuator 207. This pressure is transmitted to the relief valve 412 via the pneumatic line 636. This allows the processor to obtain an empirically calibrated relationship between the relief valve pilot pressure and PEEP. The actual pilot pressure is measured by the relief pilot valve pressure sensor 620, which is monitored by the lung console module processor 202, which also receives airway pressure measurements from the airway pressure sensor 206. In an alternative embodiment, pilot pressure measurement is used to control the pilot pressure by comparing the actual pilot pressure to a desired pilot pressure and equalizing them by changing the position of the stepper motor.

[0094] System information display and system monitoring The OCS monitor 300 is the main input and output interface for the system operator. The LCD 304 displays the relevant real-time measurements and derivations for the perfusion solution and gas loop. It also displays the status of other OCS subsystems such as battery levels and gas tank levels. The nature of the information displayed on the OCS LCD display 402 is described below. Following this, screenshots corresponding to the maintenance mode, continuous evaluation mode, and sequential evaluation mode are described.

[0095] Figure 11 is a representative screenshot of LCD 304, which corresponds to the maintenance mode. LCD 304 includes a display area 1102 that shows real-time tracking 1104 of the ventilation pressure at the lung inlet as measured by the airway pressure sensor 206. The display also includes numerical values ​​1106 and 1108 of the ventilation pressure readings, where the numerator 1106 is the peak pressure value, which is the maximum pressure sampled over the entire ventilation cycle. The denominator 1108 is the PEEP value for the last breathing cycle, which is derived by sampling the airway pressure at the end of the exhalation time, i.e., just before the inhalation of the next cycle begins. Since PEEP is defined as the pressure at the very end of the breathing cycle, it does not need to correspond to the minimum pressure during the cycle. For example, if the system exceeds or fails to reach the target when attempting to reach the PEEP setpoint, a lower pressure may occur within the system. Further numerical values ​​1110, 1112, and 1114 indicate registered setpoint (sp) values, i.e., values ​​selected by the user. The display of these values ​​helps the user compare the displayed measured respiratory pressure with a registered desired value. Value 1110 indicates the PAWP setpoint value, which is the absolute pressure upper limit or clamp for respiratory pressure. Generally, the ventilation pressure waveform is always below the PAWP limit. As previously mentioned, the PEEP setpoint 1112 corresponds to the desired respiratory pressure at the end of the respiratory cycle, after exhalation is complete and just before the inhalation pressure ramp of the next cycle begins. Value 1114 indicates I:E, which is the ratio of respiratory cycle times related to inspiration and exhalation. The inspiratory period includes both the inhalation time, i.e., the inhalation ramp 654 (Figure 6), and the plateau time 658, which correspond to the flow of gas into the lungs. Thus, I:E = (inspiratory time + plateau time) : exhalation time. The system derives the I:E value from the registered inspiratory time, plateau time, and respiratory rate.

[0096] The display area 1116 of the LCD 304 shows real-time tracking 1118 of pulmonary artery pressure (PAP) measured by the pressure sensor 115. The following PAP values ​​are also shown, which are snapshots of key values: peak or systolic pressure 1120, trough or diastolic pressure 1122, and mean perfusion pressure 1124 in the pulmonary artery supply of the lungs.

[0097] In the lower display area 1126, a time-averaged PAP graph 1128 is displayed along with a numerical value 1130 that shows the average PAP value. The selection of what to display on the LCD 304 is under the operator's control. Figure 12 shows the configuration menu 1202 with the maintenance tab 1204 selected. In this mode, the operator can select what information to display in the central graphic area 1116 and the lower graphic area 1126, respectively. The upper graphic frame 1102 is also configurable (not shown). The configuration menu's maintenance tab also provides the ability to set the average flow rate of the maintenance gas 220 through the trickle valve 212 and to control the perfusion fluid temperature. Other parameters of the lung ventilator can also be controlled from the maintenance tab menu.

[0098] LCD 304 displays several additional values ​​that give the system user a snapshot of the lung condition and OCS parameters. Display value 1160 indicates the pulmonary flow rate (PF) of the perfusion fluid into the lung 404, as measured by the flow sensor 114. Display value 1162 indicates the pulmonary vascular resistance (PVR), a measure of the resistance exerted by the lung 404 to the flow of the perfusion fluid. Generally, lower PVR values ​​are preferable, as they indicate less restrictive flow of the perfusion fluid through the vascular structure of the lung 404. In the embodiments described, favorable PVR values ​​are in the range of 200 to 400 dynes. Display value 1164 indicates the venous saturated hemoglobin content (SvO2) of the perfusion fluid 250, as measured by the oxygen sensor 116. Similarly, display value 1166 indicates the arterial saturated hemoglobin content (SaO2) of the perfusion fluid 250, as measured by the oxygen sensor 118. In certain embodiments, icons indicating SvO2 and SaO2 alarms are displayed adjacent to display values ​​1164 and 1166, respectively, to inform the operator whether either saturated hemoglobin value is below a preset threshold set by the operator. Such alarms can be triggered for any measurement, calculation, or displayed parameter. Display value 1168 indicates the hematocrit (HCT) level of the perfusion fluid 250, and optionally, an HCT alarm indicator to inform the operator whether the HCT level 1168 is below a preset threshold set by the operator. Display value 1170 indicates the temperature (Temp) 1170 of the perfusion fluid 250 as it flows away from the heater assembly 230. Display value 1170 may also include a Temp alarm indicator that alerts the operator in response to a Temp 1170 outside a preset range. A temperature setpoint 1171 selected by the operator is also indicated. Display area 1172 shows a numerical reading of the ventilation rate, measured in breaths per minute (BPM), of gas delivered to the lungs 404 via the tracheal interface 1024. The BPM value is derived from one or more inputs, including a reading from the airway pressure sensor 206. Additionally, the BPM setpoint 1173 selected by the operator is also displayed.The displayed value of 1174 represents the tidal volume (TV), that is, the amount of gas that enters the lungs (404) during each inhalation.

[0099] LCD 304 further includes a circulation pump indicator 1138 that shows the status of the system's circulation pump. Display area 1176 shows an organ type indicator 1140 that shows which organ is being perfused, and an organ mode indicator 1142 that shows which operating mode is being used. For example, "M" is used to indicate maintenance mode. SD card indicator 1144 shows whether an SD card is being used to store data collected during organ perfusion. Display area 1146 includes a gas tank diagram 1178 that graphically shows the remaining amount of maintenance gas. Display area 1146 also includes one or more display values ​​1180 that show the flow rate of gas in the gas supply source, along with the remaining time to deliver the gas to the lungs 404 during perfusion. This remaining time can be calculated based on the remaining amount of gas and the gas flow rate. Display area 1148 shows a graphical representation 1182 of the degree to which each of the batteries of the OCS console 100 is charged. Battery status symbol 1184 indicates that the battery whose status is represented graphically in 1182 is being used to power the OCS console 100. Display area 1150 shows a graphical representation 1186 of the degree to which the battery powering the user interface is charged. Display area 1188 identifies whether the OCS monitor 300 is operating wirelessly.

[0100] In other embodiments, the display screen 304 also displays the FiO2 concentration and FiCO2 concentration, which are the fractional concentrations of oxygen and carbon dioxide, respectively, measured at the tracheal inlet. The display screen 406 may further display the weight and elasticity of the lung 404, the pH of the perfusion fluid 250 circulating through the lung 1004, the partial pressure of gaseous components in the perfusion fluid 250, and the PEEP level reading.

[0101] Here, the information displayed on the OCS monitor LCD 304 will be described with respect to the operation mode of the OCS 1000. As described above, FIG. 11 shows a lung in the maintenance mode, and the values shown in the figure should be regarded as representative. As shown along the left data column, the flow rate of the perfusion fluid is 1.46 l / min, which is lower than the physiological level but sufficient to nourish the lung. As shown in the figure, the SvO2 value 1164 is 92.4% and the SaO2 value 1166 is 92.2%. These levels correspond to the equilibrium between the maintenance ventilation gas 220 and the perfusion fluid gas. The difference between the arterial oxygen level and the venous oxygen level is caused by oxygenation from the air entering the organ chamber (tending to increase SaO2) and a small amount of oxygen consumption by the lung (tending to decrease SaO2). The balance between these factors can make SaO2 higher or lower than SvO2. Generally, when the maintenance mode is fully established, the oxygen saturation values of the perfusion fluid when it enters and exits the lung are stable and equal to each other within a range of about + / -5%. When the lung consumes oxygen, oxygen is intermittently replaced by flowing the maintenance gas 220 little by little through the trickle valve 212 during each ventilation cycle. Graph 1104 shows the ventilation pressure over time, which increases when the bellows pushes air into the lung and is reduced to the desired PEEP value at the end of exhalation. The graph shows the pressure profile over the most recent ventilation cycle, and the display area 1172 indicates that the lung is ventilated at a rate of 10 breaths per minute. Graph 1118 shows the real-time PAP corresponding to the most recent ventilation cycle. The curve shows periodic peaks corresponding to the pulses of the circulation pump 226. Graph 1128 shows the PAP trend. The value 1170 is measured to be 35.0 degrees Celsius for the perfusion fluid temperature and is shown to be equal to the set point value shown at the display value 1171. Such a quasi-physiological temperature level is selected to reduce the metabolic rate of the stored lung 404. One advantage of a lower metabolic rate is the ability to reduce the amount of maintenance gas required for the lung 404, thereby enabling the lung to be stored for a longer time with a finite amount of maintenance gas 220.

[0102] Figure 13 is a representative screenshot of the OCS monitor LCD 304 when the system is in continuous evaluation mode. The respiratory graph 1302 and numerical value 1304 are similar to those shown in Figure 11 for maintenance mode. However, the PAP graph 1306 and numerical value 1308 show an average pressure of 13 mmHg, which is considerably higher than the corresponding pressure of 10 mmHg in maintenance mode. Higher pressure is required to achieve a greater flow rate of perfusion fluid through the lungs in order to enable testing of the lung's gas exchange capacity. The screen shows a flow rate of 2.93 liters / min 1310. In this mode, the gas exchanger 402 deoxygenates the perfusion fluid 250 to an SvO2 level 1312 of 82.3%. The lungs reoxygenate the blood using air ventilation to achieve an SaO2 level 1314 of 96.1%. The hematocrit level 1316 is 30%, and the perfusion fluid temperature 1318 is maintained at a physiological value of approximately 37.1°C. The respiratory rate display value 1320 shows a rate of 12 breaths per minute, which corresponds to that of the individual at rest. The tidal volume display value 1322 shows a value of 700 ml, which is well within the physiological range. The OCS status display 1324 shows a lung graphic indicating that the OCS 1000 is preserving the lungs, as well as graphics of the letters A and C indicating that the system is in continuous evaluation mode.

[0103] Although a system display corresponding to the maintenance mode and the continuous evaluation mode has been described, the inventors here explain how to display the deoxygenation phase, the holding phase, and the oxygenation phase of the sequential evaluation mode on the LCD 304. FIG. 14 is a representative screen shot of the LCD 304 when the system is in the deoxygenation phase. In this phase, the deoxygenation gas 500 passes through the gas exchanger 402 and enters the ventilation loop to the lungs 404. The oxygen level in the perfusion fluid 250 rapidly drops. This is because oxygen is removed by gas exchange in both the lungs 404 and the gas exchanger 402. Graphs 1406 and 1408 respectively show the values of SaO2 and SvO2 over approximately one minute from the start of the deoxygenation phase. As shown respectively at the right ends of graphs 1406 and 1408 and the displayed numerical values 1412 and 1410, during this time, the values drop from the upper half of the 90% range to a SaO2 value of 64.9% and a SvO2 value of 59.9%. Thus, perfusion fluid saturation levels well below the physiological range can be rapidly achieved, especially when the lungs 404 complement the gas exchange capacity of the gas exchanger 402. The ventilation pressure graph 1402 and the PAP level remain the same as those in the continuous evaluation mode. The system status display 1414 displays the lung evaluation - deoxygenation phase with the letters A, D. User - determined values regarding the deoxygenation end threshold 1416, the oxygenation phase lower limit threshold 1418, and the oxygenation phase upper limit threshold 1420 are also displayed.

[0104] Figure 15 shows a typical user interface for setting sequential evaluation parameters. Configuration mode 1502 is selected by pressing the menu button 306 on the OCS monitor 300. The user enters and applies settings in the sequential submode setting menu 1504. User-configurable values ​​are listed for the holding phase 1506, which is the time between the end of the deoxygenation phase and the start of the oxygenation phase, and the deoxygenation termination threshold 1508, which is the target minimum level of oxygen content in the perfusion fluid 250, i.e., the level at which the system stops deoxygenation when / when this level is reached. The user also sets values ​​for the oxygenation lower threshold 1510, which is the target value of perfusion fluid SvO2 in the oxygenation phase, and the oxygenation upper threshold 1512, which is the target value of perfusion fluid SaO2 in the oxygenation phase.

[0105] After the deoxygenation mode, the system enters the retention phase. Figure 16 is a representative screenshot corresponding to the retention phase. The purpose of the retention phase is to allow the oxygen level in the perfusion fluid 250 to become uniform. The extent to which this is achieved can be seen in graphs 1602 and 1604, which show the time-dependent values ​​of SaO2 and SvO2 in the perfusion fluid 250. The flat portions of both curves indicate that the saturation level is constant, and the closeness of the graphs for SaO2 and SvO2 indicates the uniformity of the saturation level on both sides of the lung 404. The displayed numerical values ​​1608 and 1606 show the values ​​of SaO2 and SvO2, respectively. As shown in Figure 16, the measured values ​​of SaO2 and SvO2 approximately 1 minute after entering the retention phase are 58.9% and 58.0%, respectively, i.e., they are very close to each other.

[0106] In the third phase of the sequential evaluation mode, the perfusion fluid 250 is reoxygenated by the lungs 404 while the system is ventilated with air. The gas exchange capacity of the lungs is related to the time required to completely reoxygenate the perfusion fluid pool. Figure 17 is a representative screenshot of the system in reoxygenation mode. Graphs 1702 and 1704 show the time-dependent values ​​of SaO2 and SvO2 in the perfusion fluid 250. Moving to the left, the graphs show the initial decrease in oxygen levels during the deoxygenation phase described earlier. The flat portion of the curve in the middle of the graph corresponds to the retention phase, which lasts for about 1 minute. The oxygenation mode begins at the right end of the flat portion of the retention phase in the graph. Shortly after switching to oxygenation mode, the graph begins to rise, which indicates oxygen gas exchange to the perfusion fluid 250 via the lungs. Graphs 1702 and 1704, and displayed values ​​1708 and 1706, show that after approximately 80 seconds of entering the oxygenation phase, the levels of SaO2 and SvO2 rose to 94.6% and 85.2%, respectively. The time required to reach the user-selected threshold oxygenation level in the perfusion fluid 250 is shown in displayed value 1710.

[0107] Here, we describe further screens for configuring the OCS 1000. Figure 18 shows the evaluation tab 1802 of the configuration menu 1202. This screen allows the user to decide what information should be displayed in the central graphic frame 1116 and the lower graphic frame 1126, set the temperature setpoint 1171, and choose whether to perform sequential or continuous evaluation mode. Tab 1802 also allows the user to select the ventilation system settings menu and the sequential evaluation submode settings.

[0108] Figure 19 shows the ventilation device settings menu 1902. Respiratory rate 1904 selects the number of ventilation cycles per minute. Tidal volume 1906 determines the amount of gas inhaled into the lungs with each breath. Inspiratory time 1908 is the duration of the inhalation phase. Peak airway pressure (PAWP) 1912 is the maximum allowable gas pressure during a respiratory cycle, which occurs while the gas is being forced into the lungs 404 by the bellows 418. PEEP 1914 controls the lung pressure at the end of exhalation.

[0109] Figure 20 shows the Lung tab 2002, which allows the user to set the Lung Mode 2004 to Maintain or Evaluate, switch the Ventilation Device Control 2006 on or off, and provides a link 2008 to the Lung Settings submenu. Figure 21 shows the System tab 2102, which allows the user to set the time and date, language, and perform other system operations. Other configuration tabs and related menus can be added based on user needs.

[0110] Organ care system console module Figure 22 is an overall view of the OCS console 100 showing a single-use disposable lung perfusion module in a semi-installed position. As broadly shown in Figure 22, the single-use disposable lung perfusion module is sized and shaped to fit and connect with the OCS console 100. Overall, the unit has a similar configuration to the organ care system described in U.S. Patent Application No. 11 / 788,865. The detachable lung perfusion module 400 is insertable into the OCS console 100 by a rotating mechanism, which allows the module 400 to slide into the lung console module from the front, as shown in Figure 22, and then rotate toward the rear of the unit. A latching mechanism 2202 secures the lung perfusion module 400 in place. In alternative embodiments, different structures and interfaces of the lung perfusion module 400 are used to connect the module to the OCS 100. When fixed in place, electrical and optical connections (not shown) provide power and communication between the OCS console 100 and the pulmonary perfusion module 400. Details of the electrical and optical connections are described in U.S. Patent Application No. 11 / 246,013, filed October 7, 2005, the entire specification of which is incorporated herein by reference. The main component of the pulmonary perfusion module 400 is the organ chamber 2204, which is described in detail below. The battery compartment 2206 and the maintenance gas cylinder 220 (not shown) are located at the base of the OCS console 100. The OCS console 100 is protected by removable panels, such as the front panel 2208. Directly below the pulmonary perfusion module are perfusion fluid sampling ports 234 and 236. An OCS monitor 300 is mounted on top of the OCS console 100.

[0111] Figure 23 is a side view of the OCS console 100. The LA sampling port 234 and PA sampling port 236 provide means for removing perfusion fluid samples or for injecting chemicals into the perfusion fluid 250. At the base of the OCS console 100, the maintenance gas tank regulator 222 and gauge 2304 are visible. A one-way inflow valve 2306, attached to the reservoir and connected to the dome of the perfusion fluid pump, is also visible.

[0112] Further system components are visible in Figure 24, a front view. The bellows 418 is located directly above the base of the OCS console module and is driven by a mechanical actuator arm 2402 connected to a ventilation unit 214 within the lung console module 200. The mechanical action of the actuator arm 2402 compresses and expands the bellows 418, thereby moving the gas flow to and from the lungs 404 during the respiratory cycle. The gas exchanger 402 is located above the bellows 418. In the described embodiment, the gas exchanger 402 is a Novalung oxygen adduct. The perfusion fluid line 2404 connects a fluid pump 226 (not shown) and a heater 230 (not shown). Directly below the organ chamber 2204, a reservoir 224 collects the perfusion fluid and connects to the pump 226 via a drain 2408 for recirculation through the system.

[0113] In Figure 25, the walls of the OCS console 100 are omitted to reveal further internal components of the system. The maintenance gas 220 is stored in a horizontally positioned cylinder, which supplies the maintenance gas 220 to the system via a regulator 222 when needed. The lung perfusion module 400 is shown in a vertical mounting position. A bellows drive plate 2502, paired with a flat disc at the end of a linear actuator 2402 (not shown), is adjacent to the bellows 418.

[0114] Figure 26 shows the OCS console 100 without the disposable lung perfusion module 400. The ventilator module 214 and mechanical actuator arm 2402 are visible. Other components of the lung console module 200 (not shown) are housed in a module mounted along the left side wall of the OCS console 100. These components are shown within the lung console module 200 in Figure 1 and include the console module controller 202, gas exchanger valve 204, airway pressure sensor 206, relief valve actuator 207, pneumatic control module 208, bellows valve actuator 210, trickle valve 212, ventilator 214, gas selector switch 216, and power converter 218. A pneumatic connector 624 provides a quick connection to the corresponding lung perfusion module connector 626. This simple connection provides gas connection to the gas exchanger 402 and further to the gas loop between the lung 404 and the bellows 418. Connectors 624 and 626 also provide a pneumatic control connection between the lung console module 200 and the lung perfusion module 400 for controlling the bellows valve 414 and the relief valve 412 and for receiving pressure data from the air sensor 206.

[0115] Figure 27 is a front view of the pulmonary perfusion module 400. The organ chamber 2204 includes a removable lid 2820 and a housing 2802. Sampling ports, including the LA sampling port 234 and the PA sampling port 236, are visible below the organ chamber 2802. The gas exchanger 402, bellows 418, and bellows plate 2502 are also visible in the figure.

[0116] The perfusion fluid circulation pathway, which was first described in relation to Figure 2 for the components of the pulmonary perfusion module 400, is now described by the inventors. A perfusion fluid reservoir 224 for storing perfusion fluid 250 is mounted below the organ chamber 2204. The perfusion fluid exits to a pump 226 (not shown) through a one-way inflow valve 2306, line 2702, and pump dome 2704. The perfusion fluid is pumped to a perfusion fluid heater 230 after passing through a perfusion fluid fluid line 2404 and compliance chamber 228. After passing through heater 230, the perfusion fluid passes through connection line 2706 to gas exchanger 402. The perfusion fluid exits gas exchanger 402 and passes through connection line 2708 to the interface with the pulmonary artery. After passing through the pulmonary vein and left atrium, the perfusion fluid is discharged from the base of the organ chamber 2204 as described below. These drains supply perfusion fluid to reservoir 224, where the cycle restarts.

[0117] Having described the OCS console 100 and the pulmonary perfusion module 400, we now describe the organ chamber 2204. Figure 28 shows an exploded view of the components of the organ chamber 2204. The base 2802 of the chamber 2204 is shaped and positioned within the pulmonary perfusion module 400 to facilitate drainage of the perfusion fluid. The organ chamber 2204 has two drains: a measuring drain 2804 and a main drain 2806 that receives the overflow from the measuring drain. The measuring drain 2804 discharges the perfusion fluid at a rate of approximately 0.5 l / min, which is considerably less than the flow rate of the perfusion fluid 250 passing through the lungs 404, which is 1.5 l / min to 4 l / min. The measuring drain leads to an oxygen probe 118 for measuring SaO2 values, and then to a reservoir 224. The main drain 2806 leads directly to the reservoir 224 without oxygen measurement. In the described embodiment, the oxygen probe 118, which is a pulse oximeter, cannot obtain an accurate measurement of the oxygen level in the perfusion fluid unless the perfusion fluid 250 is substantially bubble-free. To achieve a bubble-free perfusion fluid column, the base 2802 is formed to collect the perfusion fluid 250 discharged from the lung 404 and place it into a pool that collects the drain 2804. The perfusion fluid pool allows bubbles to dissipate before the perfusion fluid enters the drain 2804. The formation of the pool above the drain 2804 is facilitated by a wall 2808, which partially obstructs the flow of perfusion fluid from the measuring drain 2804 to the main drain 2806 until the perfusion fluid pool is large enough to ensure the dissipation of bubbles from this flow. The main drain 2806 is located lower than the measuring drain 2804; therefore, when the perfusion fluid overflows the recess surrounding drain 2804, it flows around the wall 2808 and is discharged from the main drain 2806. In an alternative embodiment of the dual drain system, another system is used to collect the perfusion fluid and put it into a pool that supplies the measuring drain. In some embodiments, the flow from the lungs is directed to a container such as a small cup that supplies the measuring drain. The cup is filled with perfusion fluid, and excess blood overflows the cup and is directed to the main drain and therefore to the reservoir pool.In this embodiment, the cup performs a function similar to that of the wall surface 2808 in the previously described embodiment, by forming a small pool of perfusion fluid from which bubbles can dissipate before the perfusion fluid flows to the measurement drain on its way to the oxygen sensor.

[0118] The lung 404 is supported by a support surface 2810. This surface is designed to support the lung 404 without applying excessive pressure, while facilitating easy drainage of the perfusion fluid by angling the lung 404 slightly downward relative to the lower lobe. The support surface includes drainage channels 2812 for collecting and channeling the perfusion fluid emanating from the lung 404, and for guiding the perfusion fluid toward a drain 2814 that directly supplies the perfusion fluid to a blood pool for measurement drain 2804. To provide further support to the lung, the lung 404 is wrapped in a polyurethane wrap (not shown) when placed on the support surface 2810. The polyurethane wrap helps anchor the lung 404, maintain the lung in its physiological configuration, and prevent the bronchi from twisting and limiting the total expansion volume. The wrap reduces the risk of the chamber applying excessive pressure to any portion of the lung 404, which could cause undesirable massive bleeding, by providing a smooth surface for the outer surface of the lung at the interface with the organ chamber 2204. The polyurethane wrap is marked with a series of lines indicating how much volume is wrapped. The desired volume of the lung to be wrapped can be determined by an empirical relationship between the size of the lung and the donor's weight. The polyurethane wrap has a series of small holes for draining the perfusion fluid that accumulates around the lung 404. The perfusion fluid is collected by a drainage channel 2812 in the support surface 2810, which channels the perfusion fluid to a drain 2814.

[0119] The upper part of the organ chamber 2204 is covered with a sealable lid, which includes a front section 2816, an upper section 2820, an inner lid (not shown) with a sterile drape, and a sealing section 2818 sealing from the front section 2816 to the upper section 2820. In an alternative embodiment, the organ chamber includes a double-lid system similar to that disclosed in connection with a cardiac preservation chamber described in U.S. Patent Application No. 11 / 245,957, which is entirely incorporated herein by reference. The double-lid system includes an outer lid, an intermediate lid, a flexible membrane, and a sealing frame between the lid and the organ chamber wall. The membrane is preferably transparent and allows a medical operator to indirectly touch / examine the lung through the membrane or apply an ultrasound probe to the lung through the membrane while maintaining the sterility of the chamber. The outer lid opens and closes on the intermediate lid independently of the intermediate lid. The outer lid is preferably sufficiently rigid to protect the lung 404 from indirect or direct physical contact. The outer lid and chamber can be made from any suitable polymer plastic, such as polycarbonate.

[0120] Covering the organ chamber helps minimize gas exchange between the perfusion fluid 250 and the ambient air, and also helps ensure that the oxygen probe measures the desired oxygen values, namely the values ​​corresponding to the perfusion fluid leaving the lungs via the LA (SaO2) and the values ​​corresponding to the perfusion fluid entering the lungs via the PA (SvO2). Closing the organ chamber 2204 also helps reduce heat loss from the lungs 404. Due to the large surface area of ​​the lungs, heat loss can be substantial. Heat loss can be a significant problem during lung transport if the OCS 1000 is placed in a relatively low-temperature environment, such as a vehicle, or outdoors when moving the OCS 1000 inside and out of a vehicle. Furthermore, prior to transplantation, the OCS 1000 may be placed in a hospital storage area or operating room, both typically with temperatures in the range of 15–22°C. At such ambient temperatures, reducing heat loss from the organ chamber 2204 is important to enable the heater 230 to maintain the desired perfusion fluid (and lung) temperature of 35–37°C. Sealing the lungs within the organ chamber 2204 also helps maintain temperature uniformity through the lungs 404.

[0121] Figure 29 is a right side view of the organ chamber 2204 with the cover removed to show the support surface 2810. Perfusion fluid drainage channels 2812 and drain 2814 deliver perfusion fluid to the housing 2802. The tracheal cannula 700 and the tracheal cannula connector 710 for connection to the OCS 1000 gas loop are also shown. As shown in Figure 8, a PA cannula 850 with double connecting tubes 852 and 854 forming a 90° angle is located above the tracheal cannula 700. A remote ventilation pressure sensor 115 (not shown) is connected to the perfusion fluid flow at the point of inflow from the PA cannula to the lung 404 by a connector 806, a pressure transducer conduit 2902, and a pressure transducer cable 2904. In Figure 30, a left side view of the organ chamber 2804, the tracheal cannula 700 is clearly visible. The tracheal cannula 700 is secured to the wall of the housing 2802 by a lock nut 708. Adjacent to the lock nut 708, a flexible urethane tube 706 protrudes into the housing 2802 of the organ chamber 2204 and leads to a silicone-coated connector 704 that connects to the trachea.

[0122] Model used Next, a typical model for using the organ care system described above for lung transplantation will be explained with reference to Figures 31 and 32.

[0123] The process of obtaining and preparing the lungs 404 for cannulation and transport begins at step 3100 by providing a suitable organ donor. The organ donor is transported to the donation site where the process of receiving and preparing the donor's lungs 404 for cannulation and transport proceeds down two intersecting paths. The paths primarily include the step of preparing the OCS 1000 to receive the donor's lungs 404, and then the step of transporting the lungs 404 to the recipient site by the OCS 1000. In particular, path 3102 includes the steps of bleeding the donor, stopping the donor's heart, and preparing the lungs 404 for cannulation into the OCS 1000. In particular, in the bleeding step 3104, the donor's blood is removed and stored so that it can be used to perfuse the lungs 404 during their maintenance on the OCS 1000. After the donor's blood has been bled, in step 3106, cardioplegic solution is injected into the donor's heart to temporarily stop its beating and prepare for the recovery of the lungs 404.

[0124] After the donor's heart has stopped, in step 3108, lung preservation solution is administered to the lungs, and then in step 3110, the lungs 404 are explanted from the donor and prepared for placement on the OCS 1000 in step 3112.

[0125] Continuing to refer to FIG. 31, after the lungs 404 have been explanted from the donor's body, in step 3124, they are attached onto the OCS 1000 by insertion into the lung chamber 2204 and cannulation with the appropriate perfusion fluid interface and gas loop interface described above.

[0126] According to another exemplary aspect, the lungs 404 can be moved directly from the donor to the OCS 1000 without using a cardiac arrest method. In a particular embodiment, the donor's lungs 404 are removed without stopping the donor's heart and subsequently attached to the OCS 1000 for maintenance.

[0127] While the lung 1004 is being prepared via route 3102, the OCS 1000 is prepared through the steps of route 3114, thereby priming it and waiting to receive the lung 404 for cannula insertion and transport as soon as the lung 404 is ready. In particular, the OCS 1000 is prepared via route 3114 through a series of steps including providing a single-use lung perfusion module 400 (step 3116), priming the OCS 1000 with maintenance fluid (step 3118), filtering blood from the donor and adding it to the reservoir 224 (step 3120), and circulating and warming the perfusion fluid within the OCS 1000 (step 3122). In certain embodiments, the perfusion fluid 250 contains whole blood. In certain embodiments, the perfusion fluid 250 is partially or completely depleted of leukocytes. In certain embodiments, the perfusion fluid 250 is platelet-depleted or platelet-free, or contains plasma substitute and is filled with red blood cells. In certain embodiments, perfusion fluid additives include prostaglandin E, prostacyclin, dextran, isuprel, floran, and nitric oxide donors, which are added while epinephrine is removed. Generally, additives can be selected from antibacterial agents, vasodilators, and anti-inflammatory agents. The additives can be delivered to the system 1000 via ports 234, 236 connected to the reservoir 224, or via an interface in the tracheal cannula 700 through a nebulizer or bronchoscope.

[0128] In stage 3126, the OCS 1000 is selected to function in maintenance mode, which is described in detail earlier. After reaching equilibrium in maintenance mode in stage 3126 and before authorizing transport to the donor site, the implanted lung 404 is evaluated in stage 3128. OCS users may choose the sequential and / or continuous evaluations described earlier.

[0129] Based on the results of the assessment performed in step 3128, and in some cases based on other monitored parameters of lung 404, it is desirable to provide treatment and supplementation to lung 404 (step 3130). The most frequently occurring pathologies in the donor lung are collapse or atelectasis. The use of OCS 1000 provides several methods for managing atelectasis. Firstly, lung 404 can be reinflated by using sign breathing, i.e., by having lung 404 take in breaths of varying tidal volumes. For example, one technique involves having lung 404 inhale a first breath with a maximum tidal volume of approximately 1000 ml, followed by two or more smaller breaths with tidal volumes as low as approximately 100 ml. A second method involves adjusting the PEEP level between values ​​in the range of approximately 2 cm to 15 cm of H2O. A third method involves restraining the overinflated area of ​​lung 404 with a polyurethane wrap used to provide support to lung 404 when placed on the support surface 2810. Such restraints allow for the intelligent application of gas loop pressure to reinflate collapsed areas of the lung. A fourth replenishment approach involves manipulating the I:E ratio to increase the amount of time spent at the pressure plateau 658 (Figure 6) to help reinflate the lung without exceeding the peak pressure 656 and PEEP level 652. Fifth, simple manipulation of the lung 404 on the support surface 2810 to change the lung's position can be an effective replenishment method. Sixth, pulmonary secretions and alveolar debris in the trachea are removed by suction using a bronchoscope. The bronchoscope is inserted into the lung 404 via a port in the connector between the tracheal cannula 700 and the gas circuit tube of the pulmonary perfusion module 400. Seventh, surfactant inhalation therapy is performed by injecting surfactant, preferably in aerosol form, into the gas line during the inhalation phase of the respiratory cycle.

[0130] Another pathology frequently observed in donor lungs is localized edema, which can occur in one or more lobes. Edema can be treated on the OCS 1000 by manipulating PEEP levels, increasing colloid osmotic pressure by ultrafiltration, and manipulating perfusion fluid pressure by vasodilators and / or pump 226 flow rates.

[0131] Pneumonia is another common pathology of the donor's lungs and can be treated by direct infusion of antibiotics into the perfusion fluid 250 and / or inhalation of these drugs through the ventilation system of the pulmonary perfusion module 400. Another supplementary technique in pneumonia is bronchoalveolar lavage.

[0132] Bronchospasm, which does not occur as frequently as the pathologies discussed earlier, is managed on OCS 1000 with inhaled bronchodilators. Bronchoscopy is optionally used to help inject bronchodilators into the airways of the lungs. Another pathology is hyperpulmonary pulmonary embolism (PAP), which is managed by adding vasodilators to perfusion fluid 250.

[0133] In some cases, the operator may perform surgery on lung 404 or administer therapeutic or other treatments such as immunosuppressive therapy, chemotherapy, genetic testing, or radiotherapy.

[0134] Generally, the lung 404 is kept in maintenance mode while replenishment is being performed. Assessment phase 3128 and replenishment phase 3130 can be repeated several times and may last up to several hours if necessary. The goal is to obtain an assessment of the lung 404 indicating that it is healthy enough to be approved for transport to the recipient site. Once this condition is met, the OCS 1000, along with its attached lung 404, is loaded onto a vehicle for transport to the recipient site.

[0135] Figure 32 shows a typical mode of use for the OCS 1000 during transport from the donor site to the recipient site. Before being placed in the transport vehicle, the OCS 1000 is placed in maintenance mode (stage 3202). The OCS 1000 is then placed in the vehicle and the journey begins (stage 3204). The lungs are evaluated after a certain time interval (stage 3206). The time interval before the first evaluation depends on the condition of the lungs 404 determined at the donor site, the parameters of the lungs 404 being monitored, and the expected duration of the journey. Generally, the worse the condition of the lungs 404, the earlier the evaluation is performed. If evaluation 3206 detects that the lungs 404 are in a poor condition, treatment and replacement are performed (stage 3210). After the replacement period, another evaluation (stage 3206) is performed. The evaluation and replacement cycle continues until evaluation stage 3206 indicates that the lungs 404 are above a certain health threshold, after which the lungs 404 are returned to maintenance mode 3208. In some embodiments, no further evaluation or replacement is performed during transport. In other embodiments, further evaluation and, if necessary, replenishment stages are performed at intervals during transport. The decision on whether or not to perform further evaluations depends on the operator's overall assessment of the health of the lungs 404 and the availability of evaluation gases in the OCS 1000. The process is completed upon arrival at the recipient site (stage 3212).

[0136] The choice of which form of assessment to perform is determined by both clinical and technical considerations. From a clinical standpoint, the saturation level of the perfusion fluid 250 is closer to the physiological blood saturation level in a continuous assessment than in a sequential assessment. On the other hand, the flow rate of the perfusion fluid is only about one-third of the physiological level in a continuous assessment, and closer to the physiological level in a sequential assessment. From a technical standpoint, the choice of assessment method may be constrained by the amount of gas available in the OCS. During the transport of the lung 404 from the donor site to the recipient site, the OCS 1000 operates self-sufficiently. In particular, it relies on its own internal supply sources of maintenance gas and deoxygenation gas. In an exemplary configuration, the OCS 1000 has a 200-liter supply source of deoxygenation gas 500. Approximately 40 liters of deoxygenation gas are required to perform a single sequential assessment of the lung. However, if the lung health is poor and gas exchange capacity is impaired, more than 40 liters of deoxygenation gas may be required for a sequential assessment. This is because it takes longer for the oxygen level in the perfusion fluid to reach the target level during the deoxygenation phase. Therefore, depending on the capacity of the deoxygenation tank, the number of sequential evaluations during the process is limited to a maximum of 5, and more generally 4 or less, depending on the state of the lungs 404. On the other hand, achieving any arbitrary target deoxygenation level in the perfusion fluid 250 is not necessary for continuous evaluation. Instead, evaluations are performed at fixed time intervals, during which the deoxygenation gas 500 flows through the gas exchanger 402 at an average rate of approximately 10 liters / minute. In an exemplary example, continuous evaluation is performed for 2 minutes, consuming a total of approximately 20 liters of deoxygenation gas 500, which is about half the amount consumed in sequential evaluation. Therefore, from a technical standpoint, continuous evaluation may be preferable to sequential evaluation. In a given process, the OCS 1000 has enough gas to enable up to 5 sequential evaluations or 10 consecutive evaluations, or any combination relating to the following equation 40s + 20c = 200, where s is the number of sequential evaluations and c is the number of consecutive evaluations.

[0137] To obtain accurate readings of oxygen levels in the perfusion fluid, the perfusion fluid column, as measured by pulse oximeters 116 and 118, should be free of gas bubbles. As previously described, the dual drain systems 2804 and 2806, as well as the perfusion fluid pool above drain 2804, help ensure that bubbles do not enter the perfusion fluid line. However, the movement of the vehicle transporting the OCS 1000 may cause sufficient agitation to expel some bubbles into the perfusion fluid column. Therefore, in the embodiments described, the vehicle is parked in a level area while the evaluation is being performed. In other embodiments, the lung chamber 2204, lung housing 2802, and dual drain systems are modified to make the system more resistant to movement, for example, by more tightly restricting the blood pool or by directly draining the perfusion fluid into the tube. Such modifications may allow for accurate lung assessment even while the transport vehicle is moving.

[0138] Figure 33 shows a typical process for performing further testing on the lung 404 while the OCS 1000 is at the recipient site. The OCS 1000 performs another assessment of the lung 404 (step 3302). Additional sources of deoxygenating gas may be available at the recipient site, which can supplement the OCS's source of deoxygenating gas 500 that may have been depleted during transport from the donor site. If the lung 404 is in poor condition, it is treated and replenished (step 3304). After the final assessment stage, if the lung 404 is assessed as being in a suitable condition for transplantation, the lung 404 is prepared for transplantation to the recipient. This includes the step of configuring the OCS 1000 for lung removal by deactivating the pump 226 to stop the flow of perfusion fluid 250 (step 3306), and optionally, the step of administering lung cessation fluid to the lung 404. Next, in step 3308, the cannula is removed from the lung 404 and the lung is removed from the lung chamber assembly 2204. In stage 3310, the transplantation of the lungs 404 into the recipient patient is performed by inserting them into the recipient's thoracic cavity and suturing the various lung connections to their appropriate corresponding connections within the recipient. In certain embodiments, a portion of the recipient's left atrium can be resected and replaced with one or more donor left atrial cuffs to which the donor's pulmonary veins are attached. In other embodiments, only one of the two lungs is removed while the remaining lung continues to be perfused and ventilated on the OCS.

[0139] While the present invention has been described in relation to various exemplary embodiments, it should be understood that the foregoing description is intended to illustrate, and not to limit, the scope of the invention as defined by the appended claims. For example, various systems and / or methods can be implemented based on this disclosure and remain within the scope of the invention. Other aspects, advantages, and modifications are within the scope of the following claims. All references cited herein are incorporated by reference in their entirety and form part of this application.

Claims

1. Methods for evaluating the lungs ex vivo, including the following: In an ex vivo perfusion system, the lung positioning step includes: Ex vivo perfusion circuit, A ventilation circuit adapted to circulate a collection volume of ventilation gas back and forth between the lungs and a variable volume chamber, and A trickle valve in fluid communication with the ventilation circuit for introducing an additional amount of ventilation gas into the collection volume; where the additional amount of ventilation gas is approximately 10% of the tidal volume; The step of circulating a perfusion fluid through the ex vivo lung, wherein the fluid enters the lung through the pulmonary artery interface and leaves the lung through the left atrial interface; The step of ventilating the lung by flowing the ventilation gas through the tracheal interface; A step of deoxygenating the perfusion fluid until the oxygen content in the perfusion fluid reaches a predetermined first value; A step of maintaining the perfusion fluid at a predetermined first value of oxygen content; The stage of interrupting ventilation or initiating a scavenging cycle; A step of re-oxygenating the perfusion fluid by ventilating the lung with an oxygenated gas until the oxygen content in the perfusion fluid reaches a predetermined second value, wherein the state of the lung can be determined based on the time required for the lung to change the oxygen content in the perfusion fluid from a first value to a second value.

2. The perfusion fluid is CO 2 The method according to claim 1, wherein the lungs are deoxygenated by ventilating them with a deoxygenating gas containing the specified substance.

3. The deoxygenated gas is 6% CO 2 The method according to claim 2, including the method described in claim 2.

4. The perfusion fluid is deoxygenated by circulating it through a gas exchange device, and the gas exchange device then... 2 and N 2 The method according to claim 1, wherein the system is in fluid communication with a deoxygenating gas containing the substance, and oxygen is removed from the perfusion fluid by gas exchange between the deoxygenating gas and the perfusion fluid.

5. The deoxygenated gas is 6% CO 2 and 94% N 2 The method according to claim 4, including the method described in claim 4.

6. The perfusion fluid is CO 2 and N 2 The method according to claim 1, wherein the lungs are deoxygenated by ventilating them with a deoxygenating gas containing the specified substance.

7. The method according to claim 1, wherein the perfusion fluid contains red blood cells, and a predetermined first value of the oxygen content in the perfusion fluid corresponds to the 73% saturation degree of red blood cells.

8. The method according to claim 1, wherein the perfusion fluid contains red blood cells, and a predetermined second value of the oxygen content in the perfusion fluid corresponds to the 93% saturation degree of the red blood cells.

9. The method according to claim 1, wherein the oxygenation gas is air.

10. The method according to claim 1, wherein the oxygenated gas contains about 25% to about 100% oxygen.

11. The method according to claim 1, wherein the perfusion fluid flows through the ex vivo perfusion circuit at a rate of approximately 1.5 liters per minute.

12. The method according to claim 1, comprising evaluating the lung while it is being transported.

13. The method according to claim 1, wherein the perfusion fluid is maintained at a temperature close to physiological temperature.

14. The method according to claim 1, wherein the perfusion fluid includes a blood product.

15. The method according to claim 14, wherein the leukocytes are at least partially depleted in the perfusion fluid.

16. The method according to claim 14, wherein platelets are at least partially depleted in the perfusion fluid.

17. The method according to claim 1, wherein the perfusion fluid contains whole blood.

18. The method according to claim 1, further comprising the step of delivering one or more therapeutic agents to the lungs during perfusion.

19. The method according to claim 18, wherein one or more therapeutic agents are selected from antibacterial agents, vasodilators, and anti-inflammatory agents.

20. The method according to claim 18, wherein one or more therapeutic agents are selected from the group consisting of prostaglandins, prostacyclins, dextran, isuprel, floran, and nitric oxide donors.

21. The method according to claim 18, wherein one or more therapeutic agents are delivered through a tracheal interface via one of a nebulizer or a bronchoscope.

22. The method according to claim 1, further comprising the step of measuring the oxygen content of a perfusion fluid in order to determine when the oxygen content of the perfusion fluid is reached to first and second predetermined values.

23. The method according to claim 22, wherein the oxygen content of the perfusion fluid is measured by determining the saturation level of red blood cells in the perfusion fluid using a pulse oximeter.

24. A system for diagnosing the lungs, including the following: A first valve configured to be coupled to a gas supply source; A gas exchanger coupled to the first valve; An ex vivo perfusion circuit for circulating perfusion fluid to the lungs, which enters the lungs through the pulmonary artery interface and leaves the lungs through the left atrial interface; A ventilation circuit for delivering ventilation gas to and from the lungs through a tracheal interface, the ventilation circuit being adapted to deliver a collection volume of ventilation gas back and forth between the lungs and a variable volume chamber; and A trickle valve in fluid communication with the ventilation circuit for introducing an additional amount of ventilation gas into the collection volume; where the additional amount of ventilation gas is approximately 10% of the tidal volume; Here, the system is configured to deoxygenate the perfusion fluid until the oxygen content in the perfusion fluid reaches a predetermined first value; The system is configured to hold the perfusion fluid at a predetermined first value of oxygen content when the first valve is closed; The system is configured to interrupt ventilation or initiate a sweep cycle when the first valve is closed and the perfusion fluid is maintained at a predetermined oxygen content; The system is configured to re-oxygenate the perfusion fluid by ventilating the lungs with an oxygenated gas until the oxygen content in the perfusion fluid reaches a predetermined second value, and The system is further configured to determine the state of the lungs based on the time it takes for the lungs to change the oxygen content in the perfusion fluid from a first value to a second value.

25. CO 2 and N 2 The system of claim 24, configured to deoxygenate a perfusion fluid by ventilating the lungs with a deoxygenating gas comprising

26. The aforementioned system, CO 2 and N 2 The system according to claim 24, wherein the perfusion fluid is deoxygenated by circulating the perfusion fluid through the gas exchanger while a deoxygenation gas containing is passed through the gas exchanger, and the gas exchanger is configured to remove oxygen from the perfusion fluid by gas exchange between the deoxygenation gas and the perfusion fluid.

27. The system according to claim 24, further comprising a second valve configured to be coupled to a ventilation circuit and to be coupled to a gas supply source, wherein when the second valve is open, the system is configured to use the lungs to deoxygenate the perfusion fluid.

28. The system according to claim 24, further comprising a ventilation device configured such that the ventilation circuit functions as a rebreather, and a second valve configured to supply a deoxygenated gas to the ventilation circuit.

29. A system for diagnosing the lungs, including the following: A first valve means configured to be coupled to a gas supply source; Gas exchange means coupled to a first valve means; Means for circulating perfusion fluid to the lungs, which enters the lungs through the pulmonary artery interface and leaves the lungs through the left atrial interface; A means of delivering ventilation gas to and from the lungs through a tracheal interface; A ventilation circuit adapted to circulate a collection volume of ventilation gas back and forth between the lungs and a variable volume chamber; and Means for introducing a further amount of ventilation gas into the collection volume, wherein the further amount of ventilation gas is approximately 10% of the tidal volume; Here, the system is configured to deoxygenate the perfusion fluid using a gas exchange means when the first valve means is open until the oxygen content in the perfusion fluid reaches a predetermined first value. When the first valve means is closed, the perfusion fluid is held at a predetermined first value of oxygen content, and when the first valve means is closed and the perfusion fluid is held at the predetermined value of oxygen content, ventilation is interrupted or a sweep cycle is started, and The system is configured to re-oxygenate the perfusion fluid by ventilating the lungs with an oxygenated gas until the oxygen content in the perfusion fluid reaches a predetermined second value. Furthermore, the system is configured to determine the state of the lungs based on the time it takes for the lungs to change the oxygen content in the perfusion fluid from a first value to a second value.

30. The system according to claim 29, further comprising a second valve means configured to be coupled to a gas supply source and to means for delivering ventilation gas to and from the lungs, wherein when the second valve means is open, the lungs are used to deoxygenate the perfusion fluid.

31. Methods for evaluating the lungs, including the following: In an ex vivo perfusion system, the lung positioning step includes the following: Ex vivo perfusion circuit; A ventilation circuit adapted to circulate a collection volume of ventilation gas back and forth between the lungs and a variable volume chamber; and A trickle valve in fluid communication with the ventilation circuit for introducing an additional amount of ventilation gas into the collection volume; where the additional amount of ventilation gas is approximately 10% of the tidal volume; The stage of circulating perfusion fluid to the lungs, which enters the lungs through the pulmonary artery interface and leaves the lungs through the pulmonary veins; In the step of circulating the perfusion fluid through a gas exchanger, the gas exchanger removes oxygen from the perfusion fluid to reduce its oxygen content; A step of ventilating the lung by flowing the ventilation gas through the tracheal interface; A step of maintaining the perfusion fluid in a state with reduced oxygen content; The stage of interrupting ventilation or initiating a scavenging cycle; A step of measuring a first value of oxygen saturation in the perfusion fluid at a certain point in the perfusion circuit after the perfusion fluid has left the lungs; and This stage assesses the condition of the lungs based on the first value of oxygen saturation.

32. The method according to claim 31, wherein the step of determining the condition of the lungs includes determining the ratio between a first value of oxygen saturation and the fraction of inspired oxygen in the ventilation gas.

33. A step of measuring a second value of oxygen saturation in the perfusion fluid at a point in the perfusion circuit near the pulmonary artery interface; and A stage in which the condition of the lungs is judged based on the difference between the first and second oxygen saturation values. The method according to claim 31, further comprising:

34. The method according to claim 31, wherein the ventilation gas is air.

35. The method according to claim 31, wherein the ventilation gas contains 25% to 100% oxygen.

36. The method according to claim 31, wherein the perfusion fluid flows through the perfusion circuit at a rate of approximately 1.5 liters per minute.

37. Methods for evaluating the lungs, including the following: In an ex vivo perfusion system, the lung positioning step includes the following: Ex vivo perfusion circuit; A ventilation circuit adapted to circulate a collection volume of ventilation gas back and forth between the lungs and a variable volume chamber; and A trickle valve in fluid communication with the ventilation circuit for introducing an additional amount of ventilation gas into the collection volume; where the additional amount of ventilation gas is approximately 10% of the tidal volume; The stage of circulating perfusion fluid to the lungs, which enters the lungs through the pulmonary artery interface and leaves the lungs through the pulmonary veins; The step of ventilating the lungs by flowing the ventilation gas through the tracheal interface; A step of deoxygenating the perfusion fluid until the oxygen saturation level in the perfusion fluid reaches a predetermined first value; A step of maintaining the perfusion fluid at a predetermined first value of oxygen content; The stage of interrupting ventilation or initiating a scavenging cycle; A step of re-oxygenating the perfusion fluid by ventilating the lungs with air until the oxygen saturation level in the perfusion fluid reaches a predetermined second value; and This stage involves determining the state of the lungs based on the time it takes for the lungs to change the oxygen saturation level in the perfusion fluid from a first value to a second value.

38. The perfusion fluid is CO 2 and N 2 The method according to claim 37, wherein the lungs are deoxygenated by ventilating them with the ventilation gas containing the above.

39. The ventilation gas is approximately 5.5% CO 2 and 94.5% N 2 The method according to claim 38, including the method described in claim 38.

40. The perfusion fluid is deoxygenated by circulating it through a gas exchange device, and the gas exchange device then... 2 and N 2 The method according to claim 37, wherein the ventilation gas containing the perfusion fluid is in fluid communication with the perfusion fluid, and the composition of oxygen in the perfusion fluid is adjusted by gas exchange between the ventilation gas and the perfusion fluid.

41. The ventilation gas is approximately 5.5% CO 2 and 94.5% N 2 The method according to claim 40, including the method described in claim 40.

42. The method according to claim 40, wherein a predetermined first value of oxygen saturation is approximately 77% oxygen.

43. The method according to claim 40, wherein a predetermined second value of oxygen saturation is approximately 97%.

44. Lung care system including the following: A first valve configured to be coupled to a gas supply source; A gas exchanger coupled to the first valve; An ex vivo perfusion circuit for circulating perfusion fluid to the lungs, which enters the lungs through the pulmonary artery interface and leaves the lungs through the left atrial interface; A ventilation circuit for delivering ventilation gas to and from the lungs through a tracheal interface, the ventilation circuit being adapted to deliver a collection volume of ventilation gas back and forth between the lungs and a variable volume chamber; and A trickle valve in fluid communication with the ventilation circuit for introducing an additional amount of ventilation gas into the collection volume; where the additional amount of ventilation gas is approximately 10% of the tidal volume; Here, the system includes a lung maintenance mode and a lung diagnostic mode. The lung maintenance mode is configured to ventilate the lungs through the tracheal interface by flowing the collected amount of ventilation gas back and forth between the lungs and the variable volume chamber, and Diagnostic mode is: The system is configured to deoxygenate the perfusion fluid using a gas exchange means while the first valve means is open until the oxygen content in the perfusion fluid reaches a predetermined first value. When the first valve is closed, the perfusion fluid is held at a predetermined first value of oxygen content. When the first valve is closed and the perfusion fluid is maintained at a predetermined oxygen content, ventilation is interrupted or a sweep cycle is initiated, and The system is configured to re-oxygenate the perfusion fluid by ventilating the lungs with an oxygenated gas until the oxygen content in the perfusion fluid reaches a predetermined second value, and The system is configured to determine the state of the lungs based on the time it takes for the lungs to change the oxygen content in the perfusion fluid from a first value to a second value.

45. The system according to claim 44, further comprising a second valve configured to be coupled to a ventilation circuit and to be coupled to a gas supply source, wherein the system is configured to deoxygenate the perfusion fluid using the lungs when the second valve means is open.

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