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rHuEPo Reduces Ischemia-Reperfusion Injury and Improves Survival After Transplantation of Fatty Livers in Rats

Background. The scarcity of appropriate donor organs remains to be a major problem in transplantation surgery today. This has led to increased acceptance of so-called marginal grafts, incorporating the increased risk of poor posttransplant function. Erythropoietin has been shown to reduce ischemia-reperfusion injury in transplanted rat livers. We investigated whether these capacities may contribute to improve marginal organ function. Methods. One hundred and forty Lewis rats were used. Fatty liver (≥50% steatosis) was induced by a special diet in 70 donor animals. Seventy recipients received liver transplantation after donor organ treatment with 1000 IU rhuEpo or saline injection (controls) into portal veins (cold ischemia 6 hr, University of Wisconsin solution). Recipients were allocated to two groups which received 1000 IU rHuEpo at reperfusion or an equal amount of saline (control). Analysis of liver enzymes, histology (hematoxylin-eosin and periodic acid Schiff stain), immunostaining (terminal deoxynucleotide tranferase- mediated dUTP nick-end labeling, hypoxyprobe, and tumor necrosis factor-&agr;), and reverse transcriptase-polymerase chain reaction of cytokine messenger RNA (interleukin-1, interleukin-6, hypoxia induced factor-1&agr;, vascular endothelial growth factor, and hepatocyte growth factor) were performed at defined time points (2, 4.5, 24, 48 hr, and 7 days postoperatively). Results. Alanine aminotransferase values were significantly reduced for epo-treated rats 48 hr after reperfusion; however, at all other time points enzyme levels were without significant differences. Terminal deoxynucleotide tranferase-mediated dUTP nick-end labeling and hypoxyprobe analysis and necrotic index evaluation displayed significant reduction of apoptosis and hypoxic cells in rHuEpo-treated graft livers. Overall survival was significantly improved among epo-treated rats. Conclusion. Erythropoietin improves marginal graft function and recipient survival after transplantation of fatty livers in rats.