INHIBITION OF FREE RADICAL GENERATION AND IMPROVED SURVIVAL BY PROTECTION OF THE HEPATIC MICROVASCULAR ENDOTHELIUM BY TARGETED ERYTHROCYTES IN ORTHOTOPIC RAT LIVER TRANSPLANTATION

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Abstract
The capacity of specifically targeted erythrocytes to inhibit free radical—mediated injury to the endothelial cell after cold preservation, and improve liver function was studied in two experimental models: An isolated perfused rat liver (IPRL) system and syngeneic orthotopic rat liver transplantation. In the IPRL model, livers were preserved in University of Wisconsin solution for 24 h at 4°C. At the end of the preservation period, livers were flushed with lactated Ringer's (control), immunoerythrocytes (IES), or blank intact erythrocytes prior to warm reperfusion for 2 h using an assanguinous Krebs-Henseleit buffer. Production of superoxide (02) anion during warm reperfusion in the IES-treated liver was reduced by 65% as compared with controls (P<0.001) and by 74% (P<0.001) when compared with blank erythrocyte-treated livers. Endothelial cell preservation, as assessed by levels of purine nucleoside phosphorylase (PNP), was much better in the IES-treated group (P<0.001) when compared with untreated livers. Hepatocellular preservation was markedly improved in the IES-treated livers. In the syngeneic liver transplantation model, livers were preserved in UW solution for 24 h at 4°C. Prior to implantation, livers were flushed with 5 ml of cold lactated Ringer's or immunoerythrocytes. Survival after three weeks was 60% in the IES-treated group and 30% in the untreated group. Survival in the IES-treated group was not significantly different from a control (no preservation) group.