Method for maintaining and/or restoring viability of organs

• US 6,977,140 B1
• Filed: 03/29/2000
• Issued: 12/20/2005
• Est. Priority Date: 09/29/1998
• Status: Expired due to Term

• Current Assignee: Lifeline Scientific, Inc. (Shanghai Genext Medical Technology Co., Ltd.)
• Original Assignee: Organ Recovery Systems, Inc. (Shanghai Genext Medical Technology Co., Ltd.)
• Inventors: Kravitz, David C., Owen, Donald R.
• Primary Examiner(s): Saucier, Sandra E.
• Application Number:
  US09/537,180
• Time in Patent Office: 2,092 Days
• Field of Search: 435/1.1, 435/1.2
• US Class Current: 435/1.2
• CPC Class Codes: A01N 1/02 Preservation of living parts
• CPC Class Codes: A01N 1/0247 for perfusion, i.e. for circulating fluid through organs, blood vessels or other living parts
• CPC Class Codes: A01N 1/0273 Transport containers A01N1/0268 takes precedence
• CPC Class Codes: G06F 16/955 using information identifiers, e.g. uniform resource locators [URL]
• CPC Class Codes: H04L 67/02 based on web technology, e.g. hypertext transfer protocol [HTTP]

Abstract

An organ perfusion apparatus and method monitor, sustain and/or restore viability of organs and preserve organs for storage and/or transport. The method includes perfusing the organ at hypothermic and/or normothermic temperatures, preferably after hypothermic organ flushing for organ transport and/or storage. The method can be practiced with prior or subsequent static or perfusion hypothermic exposure of the organ. Organ viability is restored by restoring high energy nucleotide (e.g., ATP) levels by perfusing the organ with a medical fluid, such as an oxygenated cross-linked hemoglobin-based bicarbonate medical fluid, at normothermic temperatures. In perfusion, organ perfusion pressure is preferably controlled in response to a sensor disposed in an end of tubing placed in the organ, by a pneumatically pressurized medical fluid reservoir, providing perfusion pressure fine tuning, overpressurization prevention and emergency flow cut-off. In the hypothermic mode, the organ is perfused with a medical fluid, preferably a simple crystalloid solution containing antioxidants, intermittently or in slow continuous flow. The medical fluid may be fed into the organ from an intermediary tank having a low pressure head to avoid organ overpressurization. Preventing overpressurization prevents or reduces damage to vascular endothelial lining and to organ tissue in general. Viability of the organ may be automatically monitored, preferably by monitoring characteristics of the medical fluid perfusate. The perfusion process can be automatically controlled using a control program.

Claims

1. A method of at least one of maintaining and restoring the viability of at least one organ wherein the at least one organ is a kidney subjected to a period of ischemia or hypoxia, comprising:

perfusing said at least one organ with a first medical fluid at a first temperature to at least one of maintain and restore pre-ischemia or pre-hypoxia energy levels in the organ; and

perfusing the organ with a second medical fluid containing substantially no oxygen at a second temperature to at least one of store and transport the organ, wherein said second temperature is lower than said first temperature, wherein the first temperature is from about 20°

C. to about 24°

C.

2. The method of claim 1, wherein the first temperature is 22 to 23°

C.

3. The method of claim 1, wherein the second temperature is from approximately 1°

C. to approximately 15°

C.

4. The method of claim 1, wherein the second temperature is from 4°

C. to 10°

C.

5. The method of claim 1, wherein the second temperature is at most 15°

C.

6. The method of claim 5, wherein the second temperature is from about 4°

C. to about 10°

C.

7. The method of claim 1, wherein the first temperature is about 20°

C. and the second temperature is at most 15°

C.

8. The method of claim 7, wherein the second temperature is from about 4°

C. to about 10°

C.

9. The method of claim 1, wherein the first medical fluid is an oxygenated solution.

10. The method of claim 9, wherein the first medical fluid is an oxygenated hemoglobin-based solution and the second fluid is a simple crystalloid solution augmented with antioxidants.

11. The method of claim 1, wherein the second medical fluid comprises at least one member selected from the group consisting of an oxygen carrier, a free radical scavenger, a pituitary growth factor extract and cell culture media.

12. The method of claim 11, wherein the first medical fluid comprises at least one viability marker.

13. The method of claim 1, further comprising monitoring the viability of the organ during at least one of perfusion of the organ with the first medical fluid at the first temperature and during perfusion of the organ with the second medical fluid at the second temperature.

14. The method of claim 13, wherein viability of the organ is monitored by a sensor that senses fluid characteristics indicative of organ viability and at least one of displays sensed data and relays sensed data to a microprocessor for assessment.

15. The method of claim 1, wherein the organ is perfused at the first temperature at least one of intermittently and continuously at a pressure within a range of approximately 40 to 100 mmHg.

16. The method of claim 1, wherein the organ is perfused at the second temperature at least one of intermittently and continuously at a pressure within a range of approximately 5 to 40 mmHg.

17. The method of claim 1, wherein the organ is perfused utilizing a pressure source incapable of providing pressures greater than 100 mmHg.

18. The method of claim 1, wherein the organ is perfused utilizing a pressure source incapable of providing pressures greater than 40 mmHg.

19. The method of claim 1, further comprising collecting medical fluid that has passed through the organ in a separate organ bath for each organ, removing medical fluid from each organ bath, filtering the medical fluid and returning the medical fluid to each organ bath.

20. The method of claim 1, further comprising collecting medical fluid that has passed through the organ in a separate organ bath for each organ, removing medical fluid from each organ bath and sensing characteristics of the collected medical fluid indicative of organ viability to allow a determination of whether the viability of the organ has been at least one of sustained and restored.

21. The method of claim 1, further comprising collecting medical fluid that has passed through the organ in a separate organ bath for each organ, removing medical fluid from each organ bath and filtering, degassing and oxygenating the medical fluid and then either returning the medical fluid to each organ bath or to a medical fluid reservoir based on a sensed pH level of the medical fluid.

22. The method of claim 1, further comprising prior to perfusing the at least one organ with the first medical fluid at the first temperature, maintaining the organ at a hypothermic temperature.

23. The method of claim 1, further comprising prior to perfusing the at least one organ with the first medical fluid at the first temperature, at least one of perfusing and flushing the at least one organ with a medical fluid at a hypothermic temperature to reduce or stop catabolic changes.

24. The method of claim 23, wherein said medical fluid at a hypothermic temperature comprises at least one member selected from the group consisting of antioxidants, anti-apoptic agents and agents that decrease vascular permeability.

25. The method of claim 23, wherein said medical fluid at a hypothermic temperature comprises at least one marker for viability measurement.

26. The method of claim 1, further comprising transplanting the organ into a mammal while the organ remains at the second temperature.

27. The method of claim 26, further comprising again perfusing the organ with the first medical fluid at the first temperature after the organ has been transplanted into a mammal.

28. The method of claim 26, further comprising again perfusing the organ with the first medical fluid at the first temperature prior to transplanting the organ into a mammal.

29. The method of claim 28, further comprising again perfusing the organ with the second fluid at the second temperature prior to transplanting the organ into a mammal.

30. The method of claim 1, further comprising at least one of storing and transporting the organ in an organ cassette after perfusion of the organ with the second medical fluid at the second temperature, the organ cassette including a portable housing and an organ supporting surface configured to support an organ while allowing effluent medical fluid to pass therethrough, the portable housing including openings configured to allow tubing to pass therethrough and to be connected to the organ.

31. The method of claim 1, further comprising at least one of storing and transporting the organ in an organ cassette after perfusion of the organ with the first medical fluid at the first temperature, the organ cassette including a portable housing;

an organ supporting surface; and

tubing connectable to the organ to allow perfusion of the organ.

32. The method of claim 1, wherein the organ is disposed in at least one of a portable container that is capable of maintaining the organ at a temperature of at most 15°

C. and a disposable cassette during perfusion of the organ.

33. The method of claim 1, wherein the organ is disposed in at least one of a portable container that is capable of maintaining the organ at a temperature of at most 10°

C. and a disposable cassette during perfusion of the organ.

34. The method of claim 1, further comprising placing the organ in a portable container that is capable of maintaining the organ at a temperature of at most 15°

C. to at least one of store and transport the organ.

35. The method of claim 1, further comprising placing the organ in a portable container that is capable of maintaining the organ at a temperature of at most 10°

C. to at least one of store and transport the organ.

36. The method of claim 1, further comprising placing the organ in a portable perfusion unit to at least one of store and transport the organ.

37. The method of claim 36, further comprising monitoring the location of the organ using a global positioning system.

38. The method of claim 1, further comprising placing the organ in a disposable cassette to at least one of store and transport the organ.

39. The method of claim 1, wherein the first and second fluids are the same medical fluid.

40. A method of at least one of maintaining and restoring the viability of at least one organ wherein the at least one organ is a kidney subjected to a period of ischemia or hypoxia, comprising:

perfusing said at least one organ with a medical fluid at a first temperature to at least one of maintain and restore pre-ischemia or pre-hypoxia energy levels in the organ the first temperature is from about 20°

C. to about 24°

C.; and

perfusing the organ with the medical fluid at a second temperature to at least one of store and transport the organ, wherein said second temperature is lower than said first temperature, wherein the second temperature is from about 4°

C. to about 10°

C.