Background: Ischemia-reperfusion injury (IRI) is inevitable in organtransplantation. To compensate for the shortfall in available donor kidneys,organs from donors after cardiac death (DCD) are more widely utilized.Unfortunately, DCD kidneys are more sensitive to IRI and sufferincreased delayed graft function and rejection with decreased graft survival.Modifications to existing graft perfusate/storage solutions may potentiallybenefit DCD graft outcomes. Hydrogen sulphide (H2S) is a novel endogenousmolecule which has recently gained notoriety for its protective effectsagainst hypoxia induced injury; however, its role in warm renal IRI has notyet been fully elucidated. We aimed to determine if exogenous H2S wouldaffect renal and hepatic vascular flow patterns (intravital microscopy), aswell as markers of organ function, inflammation and apoptosis in a ratmodel of warm renal IRI.Methods: Male Lewis rats were subjected to right nephrectomy followedby 1h of left renal ischemia and 2h of reperfusion while the peritoneumwas perfused with 4°C PBS (IRI, n=5) or 150 μmol/L of NaHS (IRI + H2S,n=6) and compared to Sham (n=6) animals. After reperfusion, the kidneyor liver was exteriorized for intravital microscopy video recording to assessrenal vascular and hepatic sinusoidal microcirculation. Blood was collectedfor serum AST, ALT and creatinine. Kidneys were histologically scored forapoptosis and homogenates were tested for markers of inflammation andapoptosis by real time RT-PCR.Results: Kidneys subjected to IRI showed a decrease in the proportion ofperfused peritubular capillaries (PC) and an increase in capillaries devoid ofblood flow, which were significantly improved with supplemental H2S, thispattern was also visualized in liver sinusoids. IRI showed marked elevationin creatinine, AST and ALT, which were tapered with the administrationof H2S. IRI led to increased expression of inflammatory markers (IL-2 andIFN-γ) and reduced mRNA levels of genes that encode pro-survival proteins(BCL-2, ERK-1 and ERK-2) which were all attenuated in the IRI+H2Sgroup. Histological analysis revealed decreased renal tubular apoptosis inthe IRI+H2S compared to IRI animals.Conclusions: Our findings support the protective role of supplemental H2Sin warm IRI injury and suggest that this novel mediator may have potentiallyclinical applicability in DCD models of renal transplantation as well as innephron-sparing surgery.
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