Abstract
Deterioration in mitochondrial function leads to hepatic ischemia and reperfusion injury (IRI) in liver surgery and transplantation. 3D optical cryoimaging was used to measure the levels of mitochondrial coenzymes NADH and FAD, and their redox ratio (NADH/FAD) gave a quantitative marker for hepatocyte oxidative stress during IRI. Using a rat model, five groups were compared: control, ischemia for 60 or 90 minutes (Isc60, Isc90), ischemia for 60 or 90 minutes followed by reperfusion of 24 hours (IRI60, IRI90). Ischemia alone did not cause a significant increase in the redox ratio; however, the redox ratio in both IRI60 and IRI90 groups was significantly decreased by 29% and 71%, respectively. A significant correlation was observed between the redox ratio and other markers of injury such as serum aminotransferase levels and the tissue ATP level. The mitochondrial redox state can be successfully measured using optical cryoimaging as a quantitative marker of hepatic IR injury.
Highlights
End stage liver disease is a leading cause of death in the USA
This study investigated the potential use of optical imaging for the quantitative measurement of ischemia and reperfusion injury (IRI) in liver transplantation
The results revealed that: (i) the measured redox ratio (RR) value, corresponding to the NADH/flavin adenine dinucleotide (FAD) ratio, did not change during ischemia alone, while it decreased in reperfusion phase, (ii) RR marker correlated with the degree of hepatic IRI as the ischemia period increased
Summary
End stage liver disease is a leading cause of death in the USA. One of the reasons for this shortage is ischemia and reperfusion injury (IRI) which has a significant negative impact on the organ functionality. Hepatic IRI has a profound clinical impact on graft function after LT with organs from marginal or extended criteria donors because its deleterious effects are augmented in these grafts. IRI causes early organ failure in up to 12% of patients, and 15% to 25% of patients experience long-term graft dysfunction [2]. Post-reperfusion syndrome, with an incidence rate of up to 30%, causes acute cardiovascular collapse that could lead to patient death [3]. Poor graft function after LT contributes to the need for a retransplantation of the liver and results in an increase in resource utilization
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