Effect of Nitric Oxide (NO) on Ischemic/Reperfusion Injury During Extended Donor Criteria (EDC) Liver Transplantation
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Peripheral Vascular Disease, Cardiology, Hospital |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Other |
| Healthy: | No |
| Age Range: | 18 - 69 |
| Updated: | 4/21/2016 |
| Start Date: | October 2009 |
| End Date: | March 2016 |
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.
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
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