Methods to improve organ viability
View Patent ↗The present disclosure provides methods to improve the viability of an organ, or organs, by continuously administering a composition comprising NO x gas directly to the organ(s).
1. A method for increasing superoxide dismutase 2 (SOD2 or manganese-dependent superoxide dismutase (MnSOD)) activity in an organ with ischemia-reperfusion damage, the method comprising:
continuously administering a composition comprising 20 ppm or less of NO gas directly to the organ, wherein MnSOD activity is increased in the organ compared to a control organ that has not been contacted with the composition.
2. The method of claim 1 , wherein MnSOD activity is increased by 5% to 95% in comparison to an organ treated under similar conditions, but that is not directly and continuously administered NO gas.
3. The method of claim 1 , wherein the composition comprises an acellular perfusion fluid.
4. The method of claim 3 , wherein the acellular perfusion fluid comprises sodium caprylate, N-acetyl-DL-tryptophan, and human albumin.
5. The method of claim 1 , wherein the organ is a heart, a lung, or a kidney.
6. The method of claim 1 , wherein administration of the composition is for a time necessary to improve viability of the organ.
7. The method of claim 6 , wherein administration of the composition is for 5 to 60 minutes or 1 to 12 hours.
8. The method of claim 1 , wherein administration begins at the same time as or within about 5 to 30 minutes after the start of the ischemia.
9. The method of claim 1 , wherein administration begins during reperfusion or continues for 1 to 12 hours after reperfusion has begun.
10. A method for inhibiting formation of nitrotyrosine in an organ with ischemia-reperfusion damage, the method comprising:
continuously administering a composition comprising 20 ppm or less of NO gas directly to the organ, wherein formation of nitrotyrosine adduct is inhibited in the organ compared to a control organ that has not been contacted with the composition.
11. The method of claim 10 , wherein nitrotyrosine formation is inhibited by 5% to 95% in comparison to an organ treated under similar conditions, but that is not directly and continuously administered NO gas.
12. The method of claim 10 , wherein the composition comprises an acellular perfusion fluid.
13. The method of claim 12 , wherein the acellular perfusion fluid comprises sodium caprylate, N-acetyl-DL-tryptophan, and human albumin.
14. The method of claim 10 , wherein the organ is a heart, a lung, or a kidney.
15. The method of claim 10 , wherein administration of the composition is for a time necessary to improve viability of the organ.
16. The method of claim 15 , wherein administration of the composition is for 5 to 60 minutes or 1 to 12 hours.
17. The method of claim 10 , wherein administration begins at the same time as or within about 5 to 30 minutes after the start of the ischemia.
18. The method of claim 10 , wherein administration begins during reperfusion or continues for 1 to 12 hours after reperfusion has begun.
19. A method for preventing inactivation of mitochondrial complex I activity, complex II activity, complex III activity, complex IV activity, or a combination thereof, in an organ with ischemia-reperfusion damage, the method comprising:
continuously administering a composition comprising 20 ppm or less of NO gas directly to the organ, wherein administering 20 ppm or less of NO gas prevents inactivation of activity of mitochondrial complex I, complex II, complex III, complex IV, or a combination thereof compared to a control organ.
20. The method of claim 19 , wherein inactivation of activity of mitochondrial complex I, complex II, complex III, complex IV, or a combination thereof is inhibited by 5% to 95% in comparison to an organ treated under similar conditions, but that is not directly and continuously administered NO gas.
21. The method of claim 10 , wherein the composition comprises an acellular perfusion fluid.
22. The method of claim 12 , wherein the acellular perfusion fluid comprises sodium caprylate, N-acetyl-DL-tryptophan, and human albumin.
23. The method of claim 10 , wherein the organ is a heart, a lung, or a kidney.
24. The method of claim 10 , wherein administration of the composition is for a time necessary to improve viability of the organ.
25. The method of claim 15 , wherein administration of the composition is for 5 to 60 minutes or 1 to 12 hours.
26. The method of claim 10 , wherein administration begins at the same time as or within about 5 to 30 minutes after the start of the ischemia.
27. The method of claim 10 , wherein administration begins during reperfusion or continues for 1 to 12 hours after reperfusion has begun.