Effects of endotoxin tolerance on liver function after hepatic ischemia/reperfusion injury in the rat

Objective: It is known that endotoxin tolerance prevents lethality after ischemia/reperfusion injuries (e.g., myocardial infarction) in laboratory animals. We used a rat model of partial hepatic ischemia/reperfusion to investigate whether endotoxin tolerance prevents associated lethality and disorders of liver function. Design: Prospective animal study. Setting: University research facility. Subjects: Male Sprague-Dawley rats. Interventions: Hepatic ischemia was initiated by atraumatic clipping across the portal venous and hepatic arterial blood supply to the left lateral lobe for 90 mins. The common bile duct was canalized, and in a second set of experiments the bile duct of the left lateral lobe was canalized selectively. Bile flow, bile acids, and transaminases were determined during ischemia and 300 mins of reperfusion in endotoxin-tolerant and -nontolerant rats. Measurements and Main Results: Endotoxin-nontolerant animals showed a 50% lethality after hepatic ischemia/reperfusion injuries. All endotoxin-tolerant rats survived and did not react with any change in bile flow, showing a constant flow. The amount of bile acids in the common bile duct was reduced during ischemia and regained the concentrations of sham-operated animals 60 mins after reperfusion. From 180 mins after reperfusion, the difference between endotoxin-tolerant and -nontolerant animals was statistically significant. When bile acid concentration was determined in the ischemic left lateral lobe, ischemia/reperfusion was found to significantly decrease in endotoxin-nontolerant rats 60 mins after reperfusion. In contrast, endotoxin-tolerant rats produced normal amounts of bile acids 60 mins after reperfusion. At 120 mins after reperfusion, the amount of bile acids in the formerly ischemic left lateral lobe was more than normal. Conclusions: In this model of partial hepatic ischemia/reperfusion, endotoxin tolerance prevents ischemia/reperfusion injury-associated lethality and local disorders of liver function. This phenomenon induced by endotoxin tolerance may be useful in liver surgery to prevent ischemia/reperfusion injury.