EFFECT OF PHALLOIDIN ON CHOLESTASIS, HEMODYNAMICS, AND MICROCIRCULATION IN ISOLATED-PERFUSED RAT-LIVER

In this study, the possible role of the hepatic microcirculation in ph alloidin-induced cholestasis and hepatotoxicity was examined in isolat ed perfused rat livers (IPRL). Administration of a phalloidin bolus (1 mg/kg body weight) through the portal vein induced an immediate reduc tion of bile now, In 16.9 minutes, bile now was 50% lower than basal v alues. Portal pressure was only increased in 60 minutes after phalloid in injection and increased sharply hom this time up to the end of perf usion (90 minutes), Under these conditions, phalloidin did not induce Liver cell cytolysis, as assessed by aspartate transaminase (AST) and lactate dehydrogenase (LDH) release in the perfusate effluent. Under e lectron microscopy, hepatocytic vacuolization was mild 15 minutes afte r phalloidin administration but increased with time, At the end of per fusion, the hepatic architecture was markedly altered; erythrocyte acc umulation was observed in both sinusoids and hepatocyte vacuoles, Eval uation by multiple indicator dilution curves showed that extravascular volume (EVV) was significantly affected by phalloidin. It was augment ed in 30 minutes after phalloidin administration with values increasin g gradually over time. Neither vascular nor cellular volume was altere d. The hepatic swelling may be attributed to enlargement of the extrav ascular space of the liver. These results indicate that changes in the liver microcirculation are not the primary cause of phalloidin-induce d cholestasis in the IPRL.