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 to improve the viability of an organ intended for transplant, the method comprising:
continuously administering a composition comprising an acellular perfusion solution and 20 ppm or less of NO x gas directly to the organ via an organ perfusion system or ventilation; and
administering to the organ a composition comprising about 20 ppm to about 40 ppm of NO x gas (“a loading dose”) immediately before continuously administering the composition comprising the acellular perfusion solution and 20 ppm or less of NO x gas.
2. The method of claim 1 , where in the composition is administered for at least one hour but not more than 12 hours.
3. The method of claim 1 , wherein the composition is administered after the organ has been harvested from a donor.
4. The method of claim 1 , wherein the composition is administered while the organ is within a brain dead donor.
5. The method of claim 1 , wherein the organ is selected from the group consisting of lungs, heart, liver, kidney, pancreas, intestine, thymus, and cornea.
6. The method of claim 1 , wherein the amount of NO x is about 10 ppm to about 15 ppm.
7. The method of claim 1 , wherein the amount of NO x is about 5 ppm to about 10 ppm.
8. The method of claim 1 , wherein the amount of NO x is about 1 ppm to about 5 ppm.
9. The method of claim 1 , wherein the acellular perfusion solution comprises sodium caprylate, N-acetyl-DL-tryptophan, and human albumin.
10. The method of claim 1 , wherein the loading dose is administered for up to about 1 hour (“a loading period”) immediately before continuously administering the composition comprising the acellular perfusion solution and 20 ppm or less of NO x gas.
11. The method of claim 10 , wherein the loading dose composition further comprises an acellular perfusion solution.
12. The method of claim 11 , wherein the acellular perfusion solution comprises sodium caprylate, N-acetyl-DL-tryptophan, and human albumin.
13. The method of claim 10 , wherein the total administration time of NO x gas does not exceed 12 hours.
14. The method of claim 1 , wherein mitochondrial function is significantly preserved.
15. The method of claim 1 , wherein mitochondrial reactive oxygen species (mtROS) is decreased within the organ compared to a non-treated control.
16. A method to improve the viability of an organ damaged by ischemia-reperfusion, the method comprising:
continuously administering a composition comprising an acellular perfusion solution and 20 ppm of less or less of NO x gas directly to the organ via an organ perfusion system or ventilation; and
administering to the organ a composition comprising about 20 ppm to about 40 ppm of NO x gas (“a loading dose”) immediately before continuously administering the composition comprising an acellular perfusion solution and 20 ppm or less of NO x gas.
17. The method of claim 16 , wherein the loading dose is administered for up to about 1 hour (“a loading period”) immediately before continuously administering the composition comprising the acellular perfusion solution and 20 ppm or less of NO x gas.
18. A transplantation method comprising
administering to the organ a composition comprising an acellular perfusion solution and about 20 ppm to about 40 ppm of NO x gas (“a loading dose”) immediately before step (a);
(a) continuously administering to an organ intended for transplant a composition comprising an acellular perfusion solution and 20 ppm of less of NO x gas directly via an organ perfusion system or ventilation; and
(b) transplanting the organ into a recipient.
19. The method of claim 18 , wherein the loading dose is administered for up to about 1 hour (“a loading period”) immediately before step (a).