Rapid effects of lipopolysaccharides on indocyanine green clearance in ratliver

Background Lipopolysaccharides (LPSs) are thought to be one of the triggers of organ reactions to sepsis, which causes hepatocellular dysfunction. Thi s dysfunction can be demonstrated by a reduction of organic anion transport . The aim of our study was to assess whether the transport of indocyanine g reen (ICG) is affected by LPS, and whether Kupffer cells are involved. Methods Single-pass liver perfusion with ICG at a concentration of 57.8 mg/ kg/min was performed for 130 min. pH, oxygen tension and perfusion pressure were continuously measured in influent and effluent. Taurocholate was infused at 48.3 mg/kg/min to achieve a stable bile flow. L PS was added at concentrations of 0.45, 0.9 and 1.44 mg/kg/min for 30 min. ICG was determined photometrically in perfusate and bile. To depress the fu nction of Kupffer cells male Wistar rats were treated with GdCl3 24 h in ad vance. Primary cultured hepatocytes were used for studying the direct effec t of LPS on the uptake rate of ICG. Results Forty-five minutes after administration of LPS a significant dose-d ependent decrease of ICG uptake was seen in animals treated with LPS. Liver s of animals pretreated with GdCl3 did not show this decrease. LPS had no d irect effect on the uptake of ICG into primary cultured hepatocytes, wherea s treatment of these cells with 8-bromo-cGMP resulted in a significant incr ease of ICG uptake. Conclusion LPS has a rapid dose-dependent effect on the detoxification prop erties of the liver for ICG, The rapid effect of LPS on ICG uptake in hepat ocytes is mediated by Kupffer cells. (C) 2000 Lippincott Williams & Wilkins .