Effect of graded bilirubin loads on bilirubin transport by perfused rat liver

Abstract

Features of hepatic bilirubin transport were studied with the isolated perfused rat liver. Male Wistar rats weighing 350-400 g were used as liver donors. When bilirubin was constantly infused into the perfusion medium, which contained sheep erythrocytes and 3.0 g/100 ml bovine serum albumin, the maximal excretion rate for bilirubin was 14.4 +/- 1.2 mug/min per g liver. Over a wide range of constant bilirubin infusion rates which went as high as 25.9 mug/min per g liver, there was no effect on bile flow, bile acid excretion, or the pattern of bilirubin conjugates in bile. The hepatic extraction efficiency for unconjugated bilirubin from the perfusate also remained constant averaging 26%. However, when bolus injections of bilirubin were used to produce higher levels of unconjugated bilirubin in the perfusate than could be attained during constant infusion, the disappearance rate of [14C]bilirubin from the perfusate decreased with increasing bilirubin concentrations. This was consistent with saturation of the hepatic removal of unconjugated bilirubin.