Correlation of endothelium-dependent and -independent vasodilatation with liver function tests during prolonged perfusion of the rat liver

Twelve male Wistar rats were anaesthetized with pentobarbitone (3 mg 100 g( -1) i.p.), the livers were excised and perfused in vitro through the hepati c artery and portal vein at constant flow rates of 0.32 +/- 0.01 (mean +/- S.E.) and 0.98 +/- 0.03 mi min(-1) g liver(-1), respectively. The tone of t he preparation was raised by methoxamine (7.5x10(-6) M). Responses to mid-r ange doses of acetylcholine (-11 log mel) and sodium nitroprusside (-9 log mel) produced submaximal degrees of vasodilatation (-log mol ED50 = 12.18 /- 0.08) and (-log mol ED50 = 9.95 +/- 0.23), respectively, which did not s ubside until 5.5 h of perfusion. These did not coincide with the increase i n activities of lactic acid dehydrogenase (LDH) and aspartate serine transa minase (AST) activity at 2.5 h, which were indicative of hepatocellular mit ochondrial and cytoplasmic damage, respectively. Vascular responses suggest ed that there was little deterioration in endothelial or smooth muscle func tion in the hepatic artery up to 5 h perfusion. This model can be reliably used to investigate endothelium-dependent and -independent vasodilators in vascular pharmacological studies of the rat liver although some minimal inc reases may occur in AST and LDH activity before hemodynamic changes appear at 5.5 h. (C) 1999 Elsevier Science Inc.