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The combination of hepatic ischemia and cholestasis, both identified as risk factors for oxidative stress, potentially enhances postischemic reperfusion (I/R) injury. Preoperative biliary drainage relieves oxidative stress and therefore seems a worthwhile intervention in cholestatic patients undergoing major liver resection.To assess the effect of biliary decompression on I/R injury in a reversible bile duct ligation (BDL) model in the rat.Male Wistar rats were randomized into 3 groups. The first group underwent 30 minutes of partial liver ischemia after 7 days BDL; the second group underwent internal drainage (ID) after 7 days BDL and after 5 days, were subjected to partial liver ischemia. The last group (control animals) underwent 2 sham laparotomies and subsequent ischemia. Inflammatory response (interleukin [IL]-6, IL-10, GRO/KC, and interferon-γ), hepatic damage and oxidative stress were assessed during 24 hours of reperfusion.Cholestatic rats, as compared with the ID and control groups, showed significantly increased I/R injury as determined by transaminase release, histologic injury score and neutrophil infiltration. Plasma IL-6, IL-10, and GRO/KC (a CXC chemokine) were significantly increased in the BDL group (P < .05 vs control and ID). Moreover, the hepatic antioxidant capacity was strongly decreased in the BDL group (P < .01 vs control and ID). No significant differences for most parameters were seen in the ID group as compared to the control group.The cholestatic rat is more susceptible to postischemic liver injury and these injurious effects were significantly attenuated by biliary decompression.