PROTECTION BY CYCLOSPORINE-A AGAINST NORMOTHERMIC LIVER ISCHEMIA-REPERFUSION IN PIGS

Background. Cyclosporine A (CYA) is primarily utilized as an immunosup pressant, but its mechanisms of action (including decreased neutrophil ic free radical production and stabilization of mitochondrial and lyso somal membranes) may have beneficial effects in ischemia and reperfusi on (IR) injury. This study was undertaken to examine the effect of CYA pretreatment on porcine liver histopathologic changes and enzymatic r elease caused by ischemia and reperfusion. Materials and methods. CYA was administered orally for 4 days prior to surgery in two doses (10 o r 20 mg/ kg) while controls received only the control vehicle. Pigs we re then exposed to 4 h of hepatic ischemia followed by 2 h of reperfus ion. Results. Significant decreases in AST levels compared to controls were seen in high dose CYA pigs at the end of ischemia and at 30-min intervals during the reperfusion period. Controls exhibited necrotic h epatocytes and severe inflammatory cell infiltration, while high dose CYA animals demonstrated mild inflammatory cell infiltrates. Controls had decreased survival - 20% did not survive reperfusion. Conclusions. This study indicates that CYA may be useful in decreasing initial dam age resulting from warm hepatic IR injury. (C) 1998 Academic Press.