BackgroundThe persisting organ shortage in the field of transplantation recommends the use of marginal kidneys which poorly tolerate ischemic damage. Adenosine triphosphate (ATP) depletion during cold ischemia time (CIT) is considered crucial for graft function. We tested different strategies of kidney perfusion before transplantation in the attempt to improve the technique.Material/MethodsTwenty human discarded kidneys from donors after brain death and with at least 20 hours of CIT were randomized to the following experimental groups (treatment time three-hours at 4°C): a) static cold storage (CS); b) static cold hyperbaric oxygenation (Hyp); c) hypothermic perfusion (PE); d) hypothermic perfusion in hyperbaric oxygenation (PE-Hyp); and e) hypothermic oxygenated perfusion (PE-O2).ResultsHistological results showed that perfusion with or without oxygen did not produce any endothelial damage. A depletion of ATP content following the preservation procedure was observed in CS, PE, and Hyp, while PE-Hyp and PE-O2 were associated with a net increase of ATP content with respect to baseline level. In addition, PE-Hyp was associated with a significant downregulation of endothelial isoform of nitric oxide synthase (eNOS) gene expression and of hypoxia inducible factor-1α (HIF-1α).ConclusionsHyperbaric or normobaric oxygenation with perfusion improves organ metabolic preservation compared to other methods. This approach may prevent the onset of delayed graft function, but clinical trials are needed to confirm this.
Liver ischemia-reperfusion injury is still an open problem in many clinical circumstances, including surgery and transplantation. This study investigates how mitochondrial structure, mass and oxidative phosphorylation change and may be preserved during a brief period of ischemia followed by a long period of reperfusion, an experimental model that mimics the condition to which a liver is exposed during transplantation. Livers were explanted from rats and exposed for 24 h to three different oxygen availability conditions at 4 °C. Mitochondrial mass, respiration, oxidative phosphorylation (OXPHOS), and levels of OXPHOS complexes were all significantly altered in livers stored under the currently used preservation condition of normoxia. Remarkably, liver perfusion with hyperoxic solutions fully preserved mitochondrial morphology and function, suggesting that perfusion of the graft with hyperoxic solution should be considered in human transplantation.
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