Impact of endothelin-1 on microcirculatory disturbance after partial hepatectomy under ischemia/reperfusion in thioacetamide-induced cirrhotic rats

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Endothelin (ET)-1 contributes to hepatic ischemia and reperfusion (HIR) injury in normal liver. This study was conducted to clarify the role of ET-1 in HIR injury in cirrhotic state. Hepatic ET-1 levels in cirrhotic rats were significantly higher than those in non-cirrhotic rats. Plasma and hepatic ET-1 levels at 1, 3 and 6 hours of reperfusion animals subjected to intermittent hepatic ischemia, the elevation of plasma AST levels at 1, 3 and 6 hours of reperfusion and the decline in hepatic SO2 at the end of 60-minute hepatic ischemia and after reperfusion were significantly suppressed when compared to those subjected to continuous hepatic ischemia. Pretreatment with a non-selective endothelin receptor antagonist in continuous hepatic ischemia significantly ameliorated plasma AST levels and hepatic SO2 values with less hepatic sinusoidal congestion, resulting in an improvement in the 7-day survival rate. Continuous hepatic ischemia in the cirrhotic liver has disadvantages relating to microcirculatory derrangement with more ET-1 production in partial hepatectomy. In liver surgery, pharmacological regulation of ET-1 production may lead to attenuation of reperfusion injuries for ischemically damaged cirrhotic liver.