Effect of Nitric Oxide (NO) on Ischemic/Reperfusion Injury During Extended Donor Criteria (EDC) Liver Transplantation

Investigation of the Effect of Nitric Oxide on Ischemic Reperfusion Injury During Extended Donor Criteria Liver Transplantation

In this study, the researchers propose to investigate the efficacy of inhaled nitric oxide to prevent ischemia-reperfusion (I/R) hepatocyte injury in patients who receive extended donor criteria(EDC)liver grafts based on changes in proteomic and metabolomic markers following revascularization of the donor graft.

In reviewing the literature, no uniform extended criteria donor classification exists. The characteristics most associated with liver graft failure appear to be cold ischemia time greater than 10 hours, warm ischemia time greater than 40 minutes, donor age > 55 years of age, donor hospitalization > 5 days, a donation after cardiac death (DCD) graft, and a split graft. The researchers will exclude warm ischemia time as this is impossible to predict prior to the transplantation. Any donor meeting at least one of the other criteria will be classified as an EDC donor.

Hypothesis 1: Inhaled nitric oxide will improve overall outcome of liver recipients after EDC liver transplantation

• Suppression of oxidative injury will improve graft function postoperatively as measured by International Normalized Ratio (INR) bilirubin, transaminases, and duration of hospital stay.

Hypothesis 2: The mechanisms of therapeutic efficacy of inhaled nitric oxide is based on reduction in post-reperfusion oxidative injury as readily measured by the detectable changes in the protein and metabolic profiles in plasma of patients treated with inhaled-NO

• Nuclear Magnetic Resonance (NMR)-based metabolic markers (xanthine end-products, lactate, and hepatic osmolytes) that are consistent with acute liver injury will be decreased in NO-treated recipients.
• Protein markers of reperfusion injury (argininosuccinate synthase (ASS) and estrogen sulfotransferase (EST-1) will be greater in the plasma of patients who are not treated with inhaled-NO
• Reduced oxidative injury will be reflected by a decrease in the number of mitochondrial peroxiredoxins isoforms and the number that are oxidized in NO-treated liver recipients.

Inclusion Criteria:

• Age 18 - 69 years of age
• moderate to severe liver disease (MELD score 22 to 30)
• is receiving a extended donor criteria liver graft

Exclusion Criteria:

• undergoing multi-organ transplant
• 70 years or older
• diagnosed with hepatocarcinoma
• diagnosed with either hepatopulmonary syndrome or pulmonary hypertension
• pregnant