Effect of low flow ischemia-reperfusion injury on liver function

The release of liver enzymes is typically used to assess tissue damage foll owing ischemia-reperfusion. The present study was designed to determine the impact of ischemia-reperfusion. on liver function and compare these findin gs with enzyme release. Isolated, perfused rat livers were subjected to low flow ischemia followed by reperfusion. Alterations in liver function were determined by comparing rates of oxygen consumption, gluconeogenesis, ureag enesis, and ketogenesis before and after ischemia. Lactate dehydrogenase (L DH) and purine nucleoside phosphorylase (PNP) activities in effluent perfus ate were used as markers of parenchymal and endothelial cell injury, respec tively. Trypan blue staining was used to localize necrosis. Total glutathio ne (GSH + GSSG) and oxidized glutathione (GSSG) were measured in the perfus ate as indicators of intracellular oxidative stress. LDH activity was incre ased 2-fold during reperfusion compared to livers kept normoxic for the sam e time period whereas PNP activity was elevated 5-fold under comparable con ditions. Rates of oxygen consumption, gluconeogenesis, and ureagenesis were unchanged after ischemia, but ketogenesis was decreased 40% following 90 m in ischemia. During reperfusion, the efflux rates of total glutathione and GSSG were unchanged from preischemic values. Significant midzonal staining of hepatocyte nuclei was observed following ischemia-reperfusion, whereas n ormoxic livers had only scattered staining of individual cells. Reperfusion of ischemic liver caused release of hepatic enzymes and midzonal cell deat h, however, several major liver functions were unaffected under these exper imental conditions. These data indicate that there were negligible changes in liver function in this model of ischemia and reperfusion despite substan tial enzyme release from the liver and midzonal cell death.