The invention, in various embodiments, provides systems, methods and solutions for perfusing an organ ex vivo.
대표청구항▼
1. A method for perfusing a lung ex vivo, comprising: connecting the lung within a fluid perfusion circuit,flowing a perfusion fluid into the lung through a pulmonary artery interface and away from the lung through a pulmonary vein interface,providing a respiratory gas to the lung for use in metabol
1. A method for perfusing a lung ex vivo, comprising: connecting the lung within a fluid perfusion circuit,flowing a perfusion fluid into the lung through a pulmonary artery interface and away from the lung through a pulmonary vein interface,providing a respiratory gas to the lung for use in metabolism by the lung, the respiratory gas having a pre-determined composition of oxygen,ventilating the lung through a tracheal interface, andmeasuring a level of an arterial-venous (AV) oxygen gradient between the perfusion fluid flowing into the lung and flowing out of the lung,wherein the perfusion fluid flowing into the lung includes a first gas component at a substantially constant first composition, and the perfusion fluid flowing away from the lung includes the first gas component at a substantially constant second composition. 2. The method of claim 1, wherein ventilating occurs by flowing the respiratory gas through the tracheal interface. 3. The method of claim 2, comprising removing carbon dioxide produced by the lung through the tracheal interface. 4. The method of claim 2, wherein the first composition of the first gas component is substantially equivalent to the second composition of the first gas component. 5. The method of claim 2, wherein oxygen is maintained in the perfusion fluid flowing into the lung at a partial pressure substantially equivalent to the partial pressure of oxygen in the perfusion fluid flowing out of the lung. 6. The method of claim 2, wherein carbon dioxide is maintained in the perfusion fluid flowing into the lung at a partial pressure that is substantially equivalent to the partial pressure of carbon dioxide in the perfusion fluid flowing out of the lung. 7. The method of claim 2, wherein the respiratory gas flowing through the tracheal interface includes a composition of oxygen, carbon dioxide, and an inert respiratory gas. 8. The method of claim 7, wherein the inert respiratory gas is one of nitrogen and helium. 9. The method of claim 7, wherein the respiratory gas flowing through the tracheal interface includes at least about 10% to about 20% oxygen and at least about 2% to about 8% carbon dioxide. 10. The method of claim 9, wherein the respiratory gas is about 14% oxygen and about 5% carbon dioxide. 11. The method of claim 1 comprising oxygenating the perfusion fluid to a desired level prior to initiating perfusion of the lung. 12. The method of claim 1, comprising delivering the respiratory gas from a first gas source to the perfusion fluid through a gas exchange device connected within the perfusion circuit. 13. The method of claim 12, comprising removing carbon dioxide produced by the lung through the gas exchange device. 14. The method of claim 12, wherein ventilating the lung comprises delivering an isolated gas volume through the tracheal interface. 15. The method of claim 14, wherein the isolated volume gas source is provided by a flexible bag. 16. The method of claim 14, wherein the isolated volume gas source is provided by a hose. 17. The method of claim 14, wherein the isolated volume gas source includes gas components that reach a substantially constant composition within the isolated volume by exchanging with as components in the perfusion fluid. 18. The method of claim 12, wherein the first composition of the first gas component differs from the second composition of the first gas component by an amount substantially equivalent to a quantity of the first gas component metabolized by the lung. 19. The method of claim 12, wherein the first gas source includes a composition of oxygen, carbon dioxide, and an inert respiratory gas. 20. The method of claim 19, wherein the inert respiratory gas is one of nitrogen and helium. 21. The method of claim 19, wherein the first gas source includes a composition of about 11% to about 14% oxygen and about 3% to about 7% carbon dioxide. 22. The method of claim 20, wherein the first gas source includes a composition of about 12% oxygen and about 5% carbon dioxide. 23. The method of claim 12, comprising oxygenating the perfusion fluid with a second gas source through the gas exchange device. 24. The method of claim 12, wherein oxygen is maintained during perfusion at an equilibrium partial pressure that is greater in the perfusion fluid flowing into the lung than in the perfusion fluid flowing out of the lung. 25. The method of claim 12, wherein carbon dioxide is maintained during perfusion at an equilibrium partial pressure that is lower in the perfusion fluid flowing into the lung than in the perfusion fluid flowing out of the lung. 26. The method of claim 1, wherein the first composition of the first gas component is a partial pressure that is greater than a partial pressure of the first gas component in a predetermined first level, and less than a composition of the first gas component in a predetermined second level. 27. The method of claim 26, wherein the predetermined first level is the partial pressure of the first gas component in physiologic venous blood, and the predetermined second level is the partial pressure of the first gas component in physiologic arterial blood. 28. The method of claim 26, wherein the first gas component is oxygen. 29. The method of claim 27, wherein oxygen in the perfusion fluid flowing into the lung is maintained during perfusion at a partial pressure of about 75 mmHg to about 100 mmHg. 30. The method of claim 27, wherein oxygen in the perfusion fluid flowing into the lung is maintained during perfusion at a partial pressure of about 80 mmHg to about 90 mmHg. 31. The method of claim 30, wherein oxygen in the perfusion fluid flowing into the lung is maintained during perfusion at a partial pressure of about 83 mmHg to about 85 mmHg. 32. The method of claim 1, wherein the first composition of the first gas component is a partial pressure that is less than a partial pressure of the first gas component in a predetermined first level, and greater than a composition of the first gas component in a predetermined second level. 33. The method of claim 32, wherein the predetermined first level is the partial pressure of the first gas component in physiologic venous blood, and the predetermined second level is the partial pressure of the first gas component in physiologic arterial blood. 34. The method of claim 33, wherein the first gas component is carbon dioxide. 35. The method of claim 33, wherein carbon dioxide in the perfusion fluid flowing into the lung is maintained during perfusion at a partial pressure of about 40 mmHg to about 50 mmHg. 36. The method of claim 33, wherein carbon dioxide in the perfusion fluid flowing into the lung is maintained during perfusion at a partial pressure of about 42 mmHg to about 48 mmHg. 37. The method of claim 1 comprising maintaining the perfusion fluid provided to the lung at a near physiologic temperature. 38. The method of claim 1 comprising measuring at least one of a level of oxygen saturation of blood hemoglobin and a partial pressure of oxygen in the perfusion fluid flowing into the lung. 39. The method of claim 1 comprising measuring at least one of a level of oxygen saturation of blood hemoglobin and a partial pressure of oxygen in the perfusion fluid flowing out of the lung. 40. The method of claim 1, wherein the perfusion fluid includes whole blood. 41. The method of claim 1, comprising delivering one or more therapeutics to the lung during perfusion. 42. The method of claim 41, wherein the one or more therapeutics are selected from antimicrobials, vasodilators, and anti-inflammatory drugs. 43. The method of claim 41, wherein the one or more therapeutics are selected from isuprel, flolan, prostacycline, dextran, prostaglandins, isoproterenol, bronchodilators, surfactants, pentoxifylline and nitric oxide donors. 44. The method of claim 41, wherein the one or more therapeutics are delivered through the tracheal interface through one of a nebulizer and a bronchoscope. 45. The method of claim 1, comprising at least partially depleting the perfusion fluid of leukocytes. 46. The method of claim 1, comprising at least partially depleting the perfusion fluid of platelets. 47. The method of claim 1, comprising ventilating the lung by flowing gas through the tracheal interface. 48. A method for perfusing a lung ex vivo, comprising: connecting the ex vivo lung to a fluid perfusion circuit;flowing a perfusion fluid into the ex vivo lung through a pulmonary artery interface and away from the ex vivo lung through a pulmonary vein interface, the perfusion fluid having a gas component;providing a respiratory gas to a tracheal interface of the lung, wherein: the respiratory gas is provided to the lung in periodic breaths in alternating inspiration and expiration periods;the periodic breaths have a pre-determined volume and pressure of gas;the respiratory gas has a pre-determined composition of oxygen such that i) the gas component of the perfusion fluid flowing into the ex vivo lung is substantially constant over time at a first level, and ii) the gas component of the perfusion fluid flowing out of the ex vivo lung is substantially constant over time at a second level; andmaintaining a pre-determined minimum positive end-expiratory pressure in the lung. 49. The method of claim 48 wherein the first and second levels are substantially equal. 50. The method of claim 48 further comprising selecting the pre-determined composition of oxygen in the respiratory gas in order to establish gas component equilibrium. 51. The method of claim 48, wherein carbon dioxide produced by the lung is expelled during the expiration period. 52. The method of claim 48, further comprising suspending the lung in a flexible membrane such that the flexible membrane supports the lung's weight and distributes the lung's weight across the flexible membrane. 53. The method of claim 52, further comprising suspending the lung in a membrane comprising netting. 54. The method of claim 48, further comprising placing the lung in a support structure that simulates the interior of a chest cavity.
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