EFFECT OF FASTING ON THE UPTAKE OF BILIRUBIN AND SULFOBROMOPHTHALEIN BY THE ISOLATED-PERFUSED RAT-LIVER

Background & Aims: Occurrence of hyperbilirubinemia after fasting has been recognized for many years. The pathogenesis of this syndrome is u nclear; Although recent studies suggest that increased inr intestinal deconjugation and reabsorption of bilirubin may play a major role in e stablishment of hyperbilirubinemia during fasting, other studies have suggested that fasting down-regulates intrinsic hepatocyte transport o f bilirubin. The present study was designed to examine this possibilit y in the isolated perfused rat liver. Methods: Transport of H-3-biliru bin and S-35-sulfobromophthalein (BSP) was examined in isolated perfus ed livers from 48-hour fasted or control rats using a multiple indicat or dilution technique. Data were analyzed to quantify single-pass extr action (model-independent analysis) and were also fit by computer to t he model of Goresky to quantify unidirectional fluxes. Results: Fastin g for 48 hours resulted in an approximately 40% reduction in liver wei ght but had no effect on model-dependent or model-independent paramete rs of transport, Despite the fact that the liver was smaller; single-p ass extraction of bilirubin and BSP by livers from fasted animals did not differ from control, indicating a greater efficiency at uptake of bilirubin and BSP. Conclusions: Enhanced enterohepatic circulation of bilirubin, not altered hepatic transport, is a major factor in the pat hogenesis of fasting-induced hyperbilirubinemia.