Evaluation of Changes in Hepatic Disposition of Phenolsulfonphthalein, Indocyanine Green and Fluorescein Isothiocyanate-Dextran at Low Temperatures Using a Rat Liver Perfusion System.

OBJECTIVES:The aim of this study was to determine the factor changing the hepatic disposition of a drug during hypothermia using a rat liver perfusion system.METHODS:The livers of male Wistar rats were perfused at 37, 32 or 28°C in the single-pass mode. Venous outflow dilution patterns and biliary excretion rate patterns of phenolsulfonphthalein (PSP), indocyanine green (ICG) and fluorescein isothiocyanate (FITC)-dextran (FD-4, MW 4400) after the injection of a bolus into the perfused rat liver were analysed based on statistical moment theory.KEY FINDINGS:The first-pass extraction ratio (E(h) ) of PSP was significantly decreased at 32 and 28°C compared with 37°C. The biliary recovery of PSP and its conjugate was decreased and the biliary excretion was kept at a high concentration and was prolonged by low perfusion temperatures. ICG was almost extracted by a single-pass through the liver even at 32 and 28°C. The biliary recovery of ICG was significantly decreased at low temperature. Although the distribution volume of FD-4 as a vascular reference was not changed by perfusion temperature, the E(h) of FD-4 was decreased at 28°C although not markedly.CONCLUSION:The change in hepatic disposition of a drug at low perfusion temperatures differed according to disposition processes under hypothermia.