Systems, methods, compositions and solutions for perfusing an organ

• US 20060292544A1
• Filed: 10/07/2005
• Published: 12/28/2006
• Est. Priority Date: 06/28/2005
• Status: Active Grant

• Current Assignee: TransMedics, Inc. (TransMedics Group, Inc.)
• Original Assignee: TransMedics, Inc. (TransMedics Group, Inc.)
• Inventors: Hassanein, Waleed, Khayal, Tamer, Lezberg, Paul
• Granted Patent: US 9,078,428 B2
• Time in Patent Office: Days
• US Class Current: 435/2
• 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 1/0247 for perfusion, i.e. for circulating fluid through organs, blood vessels or other living parts
• CPC Class Codes: C12M 21/08 for producing artificial tissue or for ex-vivo cultivation of tissue prostheses A61F2/00, grafts A61L27/00

Abstract

The invention, in various embodiments, provides systems, methods and solutions for perfusing an organ.

Claims

1. A composition for use in a solution for perfusing a heart, comprising one or more carbohydrates, one or more cardio stimulants, and a plurality of amino acids that do not include asparagine, glutamine, or cysteine.

2. The composition of claim 1, wherein one or more cardio stimulants includes a catecholamine.

3. The composition of claim 1, wherein one or more cardio stimulants includes epinephrine.

4. The composition of claim 1, further comprising a blood product.

5. The composition of claim 1, further comprising whole blood.

6. The composition of claim 5, further comprising whole blood that has been at least partially depleted of leukocytes.

7. The composition of claim 5, further comprising whole blood that has been at least partially depleted of platelets.

8. The composition of claim 1, further comprising a phosphate.

9. The composition of claim 1, further comprising insulin.

10. The composition of claim 1, further comprising at least one vitamin.

11. The composition of claim 1, further comprising adenosine.

12. The composition of claim 1, further comprising a magnesium ion source.

13. The composition of claim 1, further comprising epinephrine, a phosphate, insulin, a multi-vitamin, adenosine and a magnesium ion source.

14. The composition of claim 1, further comprising one or more electrolytes.

15. The composition of claim 14, wherein the one or more electrolytes includes potassium, sodium, calcium, chloride, sulfate, or a combination thereof.

16. The composition of claim 1, further comprising an immuno-suppressant.

17. The composition of claim 16, further comprising a steroid.

18. The composition of claim 1, further comprising a therapeutic.

19. The composition of claim 1, further comprising a vector loaded with one or more genes.

20. The composition of claim 1, further comprising an aqueous medium.

21. The composition of claim 1, comprising:

22. The composition of claim 21, comprising the following components in the following amounts per about 1000 mL of aqueous medium:

23. The composition of claim 22, further including a priming solution comprising the following components in the following relative amounts:

24. The composition of claim 23, wherein the priming solution further includes aqueous fluid.

25. The composition of claim 24, wherein the components of the priming solution are in relative amounts per about 500 mL of aqueous fluid.

26. The composition of claim 1, wherein the composition, when perfused with whole blood through a heart, prolongs the heart'"'"'s ability to continue beating ex-vivo at a physiological temperature.

27. A solution system for perfusing a heart, comprising

a first chamber containing a first solution that includes one or more cardio stimulants and a plurality of amino acids that do not include asparagine, glutamine, or cysteine, and

a second chamber, containing a second solution that includes one or more carbohydrates.

28. The solution system of claim 27, including a sterilization system for sterilizing the first solution and the second solution prior to using the solutions to perfuse a heart.

29. The solution system of claim 27, including a third chamber comprising a priming solution.

30. The solution system of claim 27, wherein the one or more cardio stimulants includes epinephrine.

31. The solution system of claim 27, wherein the one or more carbohydrates in the second solution includes dextrose.

32. The solution system of claim 27, wherein the first solution includes adenosine.

33. The solution system of claim 27, wherein the first solution includes insulin.

34. The solution system of claim 27, wherein the first solution includes an immuno- suppressant.

35. The solution system of claim 27, wherein the first solution includes a multi-vitamin.

36. The solution system of claim 27, further including one or more electrolytes in the first solution.

37. The solution system of claim 27, wherein the one or more electrolytes includes calcium.

38. The solution system of claim 27, wherein the solutions are combined with a blood product prior to perfusing an organ.

39. The solution system of claim 27, further comprising a therapeutic.

40. A method for perfusing a beating heart at a physiological temperature, comprising

providing a fluid for perfusing the heart, the fluid including one or more cardio stimulants, one or more carbohydrates, and a plurality of amino acids that do not include asparagine, glutamine, or cysteine,

perfusing the fluid through the heart, and

maintaining the fluid at a physiological temperature during perfusion.

41. The method of claim 40, wherein the one or more cardio stimulants includes epinephrine.

42. The method of claim 40, wherein the fluid is provided in two components, the first component including one or more carbohydrates, and the second component including one or more cardio stimulants.

43. The method of claim 40, wherein the fluid is at a pH of about 5.5 to about 6.0.

44. The method of claim 40, further including combining the fluid with a blood product to form a combined solution and perfusing the combined solution through the heart.

45. The method of claim 40, including perfusing a therapeutic through the heart.

46. A kit, comprising one or more carbohydrates, one or more cardio stimulants, a plurality of amino acids that do not include asparagines, glutamine, or cysteine, and a package.

47. A system for perfusing an organ, comprising:

an organ; and

a substantially cell-free composition, comprising one or more carbohydrates, one or more organ stimulants, and a plurality of amino acids that do not include asparagine, glutamine, or cysteine.

48. The system of claim 47, wherein the organ is a heart.

49. The system of claim 48, wherein one or more organ stimulants includes one or more cardio stimulants.

50. The system of claim 49, wherein one or more cardio stimulants includes epinephrine.

51. The system of claim 48, wherein the heart is a beating heart.