DECREASED BILIRUBIN TRANSPORT IN THE PERFUSED LIVER OF ENDOTOXEMIC RATS

Background/Aims: Hyperbilirubinemia associated with sepsis is frequent ly observed in humans. In this study, an experimental rat model was de veloped to study bilirubin metabolism and transport during endotoxemia . Methods: Rats were injected intravenously with a single bolus of lip opolysaccharide (1 mg/kg); after 18 hours, the liver was removed for s ingle-pass perfusion. Unconjugated bilirubin, bilirubin ditaurate (125 nmol/min), and/or taurocholate (1.5 mu mol/min) were infused. Rate co nstants for uptake were determined from the disappearance of a bolus o f bilirubin ditaurate in a recirculating perfusion. Results: In endoto xemic livers, biliary excretion of bilirubin-glucuronides was reduced by 49% (2.04 +/- 0.2 and 3.99 +/- 0.24 nmol.min(-1).g liver(-1)). Simi lar results were obtained with bilirubin ditaurate, indicating that th e reduced transport is not caused by a reduced conjugation capacity. T he rate constant of sinusoidal uptake was significantly reduced during endotoxemia (0.191 +/- 0.034 vs. 0.090 +/- 0.035, respectively). Secr etion of taurocholate into bile was also reduced (92 +/- 22 vs. 127 +/ - 10 nmol.min(-1).g liver(-1)). Conclusions: In endotoxemic rats, bili ary clearance of bilirubin and taurocholate is substantially decreased , suggesting that decreased output of bilirubin-glucuronides is not ca used by impaired conjugation but by a reduction in transport.