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Am J Physiol Gastrointest Liver Physiol 280: G858-G865, 2001;
0193-1857/01 $5.00
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Vol. 280, Issue 5, G858-G865, May 2001

Endotoxin-induced reduction in biliary indocyanine green excretion rate in a chronically catheterized rat model

David W. A. Beno, Michael R. Uhing, Masakatsu Goto, Yong Chen, Vanida A. Jiyamapa-Serna, and Robert E. Kimura

Section of Neonatology, Department of Pediatrics, Rush Children's Hospital, Rush Presbyterian St. Luke's Medical Center, Chicago, Illinois 60612

Using a nonstressed chronically catheterized rat model in which the common bile duct was cannulated, we studied endotoxin-induced alterations in hepatic function by measuring changes in the maximal steady-state biliary excretion rate of the anionic dye indocyanine green (ICG). Biliary excretion of ICG was calculated from direct measurements of biliary ICG concentrations and the bile flow rate during a continuous vascular infusion of ICG. Despite significant elevations in mean peak serum tumor necrosis factor-alpha (TNF-alpha ) concentrations (90.9 ± 16.2 ng/ml), there was no effect on mean rates of bile flow or biliary ICG clearance after administration of 100 µg/kg endotoxin at 6 or 24 h. Significant differences from mean baseline rates of bile flow and biliary ICG excretion did occur after administration of 1,000 µg/kg endotoxin (mean peak TNF-alpha 129.6 ± 24.4 ng/ml). Furthermore, when rats were treated with up to 16 µg/kg of recombinant TNF-alpha , there was no change in mean rates of bile flow or ICG biliary clearance compared with baseline values. These data suggest that the complex regulation of biliary excretion is not mediated solely by TNF-alpha .

tumor necrosis factor-alpha ; hepatocellular dysfunction; sepsis; cholestasis; in vivo studies


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