Systems and methods for ex-vivo organ care

• US 20070190636A1
• Filed: 10/07/2005
• Published: 08/16/2007
• Est. Priority Date: 10/07/2004
• Status: Active Grant

• Current Assignee: TransMedics, Inc. (TransMedics Group, Inc.)
• Original Assignee: TransMedics, Inc. (TransMedics Group, Inc.)
• Inventors: Menn, Dmitri, Kyi, Stanley, Hassanein, Waleed, Khayal, Tamer, Newell, Scott, Taylor, Ronald, Goff, Larry, Bringham, Richard, Fishman, Robert, Cecere, Giovanni, Ochs, Burt, Havner, Robert, Bishop, Thomas, Algamil, Hassam
• Granted Patent: US 7,651,835 B2
• Time in Patent Office: Days
• US Class Current: 435/284.1
• CPC Class Codes: A01N 1/02 Preservation of living parts
• CPC Class Codes: A01N 1/0226 Physiologically active agents, i.e. substances affecting physiological processes of cells and tissue to be preserved, e.g. anti-oxidants or nutrients
• CPC Class Codes: A01N 1/0242 Apparatuses, i.e. devices used in the process of preservation of living parts, such as pumps, refrigeration devices or any other devices featuring moving parts and/or temperature controlling components
• CPC Class Codes: A01N 1/0247 for perfusion, i.e. for circulating fluid through organs, blood vessels or other living parts

Abstract

The invention provides, in various embodiments, systems, devices and methods relating to ex-vivo organ care. In certain embodiments, the invention relates to maintaining an organ ex-vivo at near-physiologic conditions.

Claims

1. A method of preserving a heart ex vivo comprising,

placing a heart in a protective chamber of a portable organ care system,

pumping a perfusion fluid to the heart, the perfusion fluid being at a temperature of between about 25°

C. and about 37°

C., and at a volume of between about 200 ml/min and about 5 L/min,

monitoring one or more physiologic characteristics of the heart while it is beating in the protective chamber, and

adjusting a pumping characteristic based at least in part on the physiologic characteristics to preserve the heart ex vivo.

2. The method of claim 1, wherein the physiologic characteristics include electrical characteristics.

3. The method of claim 1, wherein the physiologic characteristics include pressure characteristics.

4. The method of claim 1, wherein the perfusion fluid is blood product based.

5. The method of claim 1, wherein the perfusion fluid is synthetic blood substitute based.

6. The method of claim 1 comprising pumping the perfusion fluid with a pulsatile pump.

7. The method of claim 1, wherein the physiologic characteristics include a rate at which the heart is beating, the pumping characteristic includes a rate at which the pulsatile pump pumps, and the method includes adjusting the rate of the pulsatile pump in response to the rate at which the heart is beating.

8. The method of claim 1, wherein the physiologic characteristics include a rate at which the heart is beating, the pumping characteristic includes a stroke volume at which the pulsatile pump pumps, and the method includes adjusting the stroke volume of the pulsatile pump in response to the rate at which the heart is beating.

9. The method of claim 1, wherein the pumping characteristic includes a time at which the pump pumps the perfusion fluid into the heart, the physiologic characteristics include a representation of a portion of the heart being in a diastolic state, and the method includes pumping the perfusion fluid to the heart during the diastolic state of the portion of the heart.

10. The method of claim 9, wherein the diastolic state is a diastolic state of a ventricle of the heart.

11. The method of claim 10, wherein the ventricle is the a left ventricle.

12. The method of claim 9, wherein the diastolic state is a diastolic state of an atrium of the heart.

13. The method of claim 12, wherein the atrium is a right atrium.

14. The method of claim 1, wherein the pumping characteristic includes a shape of waveform representative of a rate and stroke volume at which a pump pumps the perfusion fluid to the heart, and the method includes altering the shape of the waveform in response to the physiologic characteristics of the heart.

15. The method of claim 1, wherein the pumping characteristic includes a flow volume of fluid per unit time at which the pump pumps the perfusion fluid, and the method includes altering the flow volume in response to the physiologic characteristics of the heart.

16. The method of claim 1, wherein the physiologic characteristics include an r-wave from the heart and the method includes synchronizing pumping of the perfusion fluid with the r-wave.

17. The method of claim 1, wherein the physiologic characteristics include an r-wave from the heart and the method includes synchronizing pumping of the perfusion fluid with the r-wave, adjusted by a user selectable pumping delay.

18. The method of claim 1 comprising flowing the perfusion fluid through a channel formed between two heated plates of a perfusion fluid heater to maintain the perfusion fluid at a temperature of between about 32°

C. and about 37°

C.

19. The method of claim 18 comprising monitoring the temperature of the perfusion fluid as it enters the channel.

20. The method of claim 18 comprising monitoring the temperature of the perfusion fluid as it exits the channel.

21. The method of claim 18 comprising monitoring temperature of at perfusion fluid heater.

22. The method of claim 1 comprising isolating a pump driver from the perfusion fluid for performing the pumping.

23. The method of claim 1 comprising,

pumping the perfusion fluid to the coronary sinus of the heart via retrograde perfusion of an aorta of the heart,

providing a flow of the perfusion fluid away from the heart via a right ventricle of the heart, and

providing a flow volume of between about 200 ml/min and about 400 ml/min of the perfusion fluid to the heart.

24. The method of claim 23 comprising maintaining the pumping of the perfusion fluid into the heart via the aorta and the flow of perfusion fluid away from the heart via the right ventricle for greater than about 2 hours while maintaining the heart in suitable condition for transplantation.

25. A method of preserving a heart ex vivo comprising,

placing a heart on one or more electrodes in a protective chamber of a portable organ care system,

pumping a perfusion fluid to the heart, the perfusion fluid being at a temperature of between about 25°

C. and about 37°

C., and at a volume of between about 200 ml/min and about 5 L/min, and

monitoring electrical signals from the electrodes while pumping the perfusion fluid to the heart to preserve the heart ex vivo.

26. The method of claim 25, wherein the electrical signals include a representation of a rate at which the heart is beating, and the method includes adjusting a rate at which the perfusion fluid is pumped to the heart in response to the rate at which the heart is beating.

27. The method of claim 25, wherein the electrical signals include a representation of a rate at which the heart is beating, and the method includes adjusting a volume of perfusion fluid pumped to the heart in response to the rate at which the heart is beating.

28. The method of claim 25, wherein the electrical signals include a representation of a portion of the heart being in a diastolic state, and the method includes pumping the perfusion fluid to the heart during the diastolic state of the portion of the heart.

29. The method of claim 28, wherein the diastolic state is a diastolic state of a ventricle of the heart.

30. The method of claim 29, wherein the ventricle is the a left ventricle.

31. The method of claim 28, wherein the diastolic state is a diastolic state of an atrium of the heart.

32. The method of claim 31, wherein the atrium is a right atrium.

33. The method of claim 25, wherein the pumping characteristic includes a shape of waveform representative of a rate and stroke volume at which a pump pumps the perfusion fluid to the heart, and the method includes altering the shape of the waveform in response to the physiologic characteristics of the heart.

34. The method of claim 25, wherein the pumping characteristic includes a flow volume of fluid per unit time at which the pump pumps the perfusion fluid, and the method includes altering the flow volume in response to the physiologic characteristics of the heart.

35. The method of claim 25, wherein the physiologic characteristics include an r-wave from the heart and the method includes synchronizing pumping of the perfusion fluid with the r-wave.

36. The method of claim 25, wherein the physiologic characteristics include an r-wave from the heart and the method includes synchronizing pumping of the perfusion fluid with the r-wave, adjusted by a user selectable pumping delay.

37. The method of claim 25 comprising,

pumping the perfusion fluid into the heart via retrograde perfusion of an aorta of the heart,

providing a flow of the perfusion fluid away from the heart via a right ventricle of the heart, and providing a flow volume of between about 200 ml and about 400 ml of the perfusion fluid to the heart.

38. The method of claim 25 comprising maintaining the pumping of the perfusion fluid into the heart via the aorta and the flow of perfusion fluid away from the heart via the right ventricle greater than about 2 hours while maintaining the heart in suitable condition for transplantation.

39. The method of claim 25, wherein the physiologic characteristics include an r-wave from the heart and the method includes synchronizing pumping of the perfusion fluid with the r-wave.

40. The method of claim 25, wherein the physiologic characteristics include an r-wave from the heart and the method includes synchronizing pumping of the perfusion fluid with the r-wave, adjusted by a user selectable pumping delay.

41. The method of claim 25 comprising flowing the perfusion fluid through a channel formed between two heated plates of a perfusion fluid heater to maintain the perfusion fluid at a temperature of between about 32°

C. and about 37°

C.

42. The method of claim 41 comprising monitoring the temperature of the perfusion fluid as it enters the channel.

43. The method of claim 41 comprising monitoring the temperature of the perfusion fluid at it exits the channel.

44. The method of claim 41 comprising monitoring temperature of the perfusion fluid heater.

45. A method of transporting a heart ex vivo comprising,

placing a heart for transplantation in a protective chamber of a portable organ care system,

pumping a perfusion fluid into the heart via retrograde perfusion of an aorta of the heart,

providing a flow of the perfusion fluid away from the heart via a right ventricle of the heart, and

transporting the heart in the portable organ care system from a donor site to a recipient site while pumping the perfusion fluid into the heart via retrograde perfusion of the aorta and providing the flow of the perfusion fluid away from the heart via the right ventricle.

46. The method of claim 45 comprising monitoring physiologic parameters of the heart while transporting it.

47. The method of claim 46, wherein the physiologic parameters include a rate at which the heart is beating, and the method includes adjusting a rate at which the perfusion fluid is pumped to the heart in response to the rate at which the heart is beating.

48. The method of claim 46, wherein the physiologic parameters include a rate at which the heart is beating, and the method includes adjusting a volume of perfusion fluid pumped to the heart in response to the rate at which the heart is beating.

49. The method of claim 46, wherein the physiologic parameters include a representation of a portion of the heart being in a diastolic state, and the method includes pumping the perfusion fluid to the heart during the diastolic state of the portion of the heart.

50. The method of claim 49, wherein the diastolic state is a diastolic state of a ventricle of the heart.

51. The method of claim 50, wherein the ventricle is the a left ventricle.

52. The method of claim 49, wherein the diastolic state is a diastolic state of an atrium of the heart.

53. The method of claim 51, wherein the atrium is a right atrium.

54. The method of claim 45 comprising maintaining the pumping of the perfusion fluid into the heart via the aorta and the flow of perfusion fluid away from the heart via the right ventricle for greater than about two hours while maintaining the heart in suitable condition for transplantation.

55. The method of claim 45, wherein the physiologic characteristics include an r-wave from the heart and the method includes synchronizing pumping of the perfusion fluid with the r-wave.

56. The method of claim 45, wherein the physiologic characteristics include an r-wave from the heart and the method includes synchronizing pumping of the perfusion fluid with the r-wave, adjusted by a user selectable pumping delay.

57. The method of claim 45 comprising flowing the perfusion fluid through a channel formed between two heated plates of a solid state heater to maintain the perfusion fluid at a temperature of between about 32°

C. and about 37°

C.

58. The method of claim 45 operating a flow switch external to the protective chamber to alter a flow of the perfusion fluid such that the perfusion fluid is pumped into the heart via a left atrium of the heart and is flowed away from the heart via the right ventricle and a left ventricle of the heart.

59. The method of claim 58 comprising performing the operating step subsequent to arrival at the recipient site.

60. A method of preserving a heart ex vivo comprising,

placing a heart in a protective chamber of a portable organ care system,

providing a perfusion fluid to the heart while the heart is in the protective chamber, and

flowing the perfusion fluid to the heart through a channel formed between two heated plates to heat the perfusion fluid to a temperature of between about 32°

C. and about 37°

C. to preserve the heart ex vivo.

61. The method of claim 60 comprising monitoring the temperature of the perfusion fluid as it enters the channel.

62. The method of claim 60 comprising monitoring the temperature of the perfusion fluid at it exits the channel.

63. The method of claim 60 comprising monitoring temperature of at least one of the heated plates.

64. A method of evaluating a heart for transplantation comprising,

placing a heart in a protective chamber of a portable organ care system,

pumping a perfusion fluid into the heart via retrograde perfusion of an aorta of the heart,

providing a flow of the perfusion fluid away from the heart via a right ventricle of the heart,

transporting the heart via the portable organ care system from a donor site to a recipient site while pumping the perfusion fluid into the heart via the aorta and providing the flow of the perfusion fluid away from the heart via the right ventricle,

prior to transplanting the heart into a recipient, operating a flow control external to the protective chamber to alter a flow of the perfusion fluid such that the perfusion fluid is pumped into the heart via a left atrium of the heart and is flowed away from the heart via the right ventricle and the left ventricle of the heart, and

performing an evaluation of the heart.

65. The method of claim 64 wherein the evaluation of the organ includes performing an echocardiogram on the heart.

66. The method of claim 64 wherein the evaluation of the organ includes measuring arterial blood gases.

67. The method of claim 64 wherein the evaluation of the organ includes performing an HLA matching test.

68. A method of providing therapy to a heart comprising,

placing a heart in a protective chamber of a portable organ care system,

pumping a perfusion fluid into the heart via retrograde perfusion of an aorta of the heart,

providing a flow of the perfusion fluid away from the heart via a right ventricle of the heart, and

administering one or more of immunosuppressive treatment, chemotherapy, gene therapy and irradiation therapy to the heart while the perfusion fluid is pumped into the heart via retrograde perfusion of the aorta.

69. A method of transplanting a heart comprising,

arresting a heart of a donor,

explanting the heart from the donor,

transferring the heart to an organ care system,

pumping a perfusion fluid to the heart in less than 30 minutes after explanting the heart from the donor, the perfusion fluid being at a temperature of between about 32°

C. and about 37°

C.

70. The method of claim 69 comprising bringing the heart to a temperature of between about 34°

C. and about 37°

C. in less than about 25 minutes after transferring the heart to the organ care system.

71. The method of claim 69 comprising bringing the heart to a temperature of between about 34°

C. and about 37°

C. in less than about 20 minutes after transferring the heart to the organ care system.

72. The method of claim 69 comprising bringing the heart to a temperature of between about 34°

C. and about 37°

C. in less than about 18 minutes after transferring the heart to the organ care system.

73. The method of claim 69 comprising bringing the heart to a temperature of between about 34°

C. and about 37°

C. in less than about 15 minutes after transferring the heart to the organ care system.

74. The method of claim 69 comprising bringing the heart to a temperature of between about 34°

C. and about 37°

C. in less than about 10 minutes after transferring the heart to the organ care system.

75. A method of transplanting a heart comprising,

explanting the heart from the donor and transferring the heart to an organ care system without arresting the heart, and

pumping a perfusion fluid to the heart in less than 30 minutes after explanting the heart from the donor, the perfusion fluid being at a temperature of between about 32°

C. and about 37°

C.

76. The method of claim 75 comprising bringing the heart to a temperature of between about 34°

C. and about 37°

C. in less than about 10 minutes after transferring the heart to the organ care system.

77. The method of claim 76 comprising bringing the heart to a temperature of between about 34°

C. and about 37°

C. in less than about 5 minutes after transferring the heart to the organ care system.

78. A method of evaluating a heart for transplantation comprising,

placing a heart in a protective chamber of a portable organ care system,

pumping a perfusion fluid into the heart via a ventricle of the heart for a period of at least about 12 hours, the perfusion fluid being at a temperature of between about 32°

C. and about 37°

C., and

performing an HLA test on the heart while the perfusion fluid is pumping.