A NOVEL HYDROXYL RADICAL SCAVENGER, NICARAVEN, ATTENUATES ISCHEMIA REPERFUSION INJURY OF THE LIVER

Abstract

278 Protection of the liver against ischemia and reperfusion (R/I) injury is essential to achieve satisfactory outcome after liver transplantation. Although various factors have been proposed to explain hepatic R/I injury, reactive oxygen substance of the cellular membrane and such cellular components has been considered and to play a crucial role. But enhancement of the defense system by supplementation of various antioxidants has been applied, it has only limited effect due to small range of biological activity and/or restricted distribution of each agents in the biological system. Nicarven (AVS) is a novel hydroxyl radical (• OH) scavenger which has both hydrophilic and lipophilic property and permeates evenly into cellular and extracellular space. Using two-hour total hepatic vascular exclusion model in dogs, we tested our hypothesis that the administration of a novel •OH scavenger would attenuate I/R injury of the liver. After skeltonization, the liver was made totally ischemic for 2 hours by cross-clamping the portal vein, the hepatic artery, and the vena cava (above and below the liver). Veno-venous bypass was used to decompress splancnic and inferior systemic venous congestion. Seventeen beagle dogs were divided into two groups 6 animals treated with AVS (Group A), and 11 with no treatment(Group C). AVS was administered intravenously at a rate of 2mg/kg/min for 60 minutes before ischemia and 3 hours after reperfusion. Animal survival, hepatic tissue blood flow (HTBF), tissue high energy phosphate level and liver enzymes level were determined. Histopathologically, severity of sinusoidal and parenchymal damages, and the number of infiltrated polymorphonuclear cells in the postischemic liver tissue were analyzed. AVS allowed survival of the all animals (6/6, 100%), while only 3 control animals lived for 2 weeks (3/11,27%p<0.01). In addition, treatment remarkably augmented HTBF and reduced hepatocyte injury. Any adverse effect was not observed in the animals treated with AVS.FigureIschemia and reperfusion injury of the liver was markedly attenuated by AVS, indicating it as a promising agent for improved presevation of hepatic graft.