Studies on the effect of synthetic amino acid mixtures on bile secretion in the isolated perfused rat liver

Abstract

Intrahepatic cholestasis may occur in patients receiving parenteral nutrition. Recent work has implicated amino acids in the perfusates in the pathogenesis of this cholestasis. Thus, we examined the effect of currently used amino acid solutions on liver structure and function using the perfused rat liver. Livers from male rats were perfused with Kreb's-Ringer bicarbonate buffer for periods up to 90 min. Two different solutions (Travasol R, Vamin R) were each added to the perfusion medium at amino acid concentrations of 0.05%, to 1.5%. The perfusate was sampled every 15 min for GTP, K + and Na +. Bile flow and bile acid secretion rate were monitored every 15 min. Livers were examined by light and electron microscopy. Infusion of amino acids did not change Na + and K + concentrations in the perfusate but decreased transaminases at all times studied. Bile flow decreased by 20% to 98% in a dose-dependent manner with Vamin R being slightly less cholestatic than Travasol R. Bile acid independent flow (BAIF) of the bile secreted was also reduced. The hepatic ultrastructure following amino acid perfusion was similar to that of livers after buffer alone and indicated absence of cellular damage. This study suggests that the amino acid solutios may induce cholestasis by interfering with the BAIF.