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 (>or=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 transferase- mediated dUTP nick-end labeling, hypoxyprobe, and tumor necrosis factor-alpha), and reverse transcriptase-polymerase chain reaction of cytokine messenger RNA (interleukin-1, interleukin-6, hypoxia induced factor-1 alpha, 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 transferase-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.


CONCLUSIONS
Erythropoietin improves marginal graft function and recipient survival after transplantation of fatty livers in rats.
Schmeding
Maximilian
M
Department of General and Transplantation Surgery, Charité University Medical Centre Berlin, Campus Virchow Clinic, Berlin, Germany. maximilian.schmeding@charite.de
Rademacher
Sebastian
S
Boas-Knoop
Sabine
S
Roecken
Christoph
C
Lendeckel
Uwe
U
Neuhaus
Peter
P
Neumann
Ulf P
UP
D000818:Animals; D004921:Erythropoietin / Q000627:therapeutic use*; D005234:Fatty Liver / Q000601:surgery*; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects*; D017228:Hepatocyte Growth Factor / Q000235:genetics; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016031:Liver Transplantation / Q000276:immunology* / Q000401:mortality; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000627:therapeutic use; D015996:Survival Rate; D017741:Survivors; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; D017228:Hepatocyte Growth Factor