Comparative endotoxin-induced hepatic injury in young and aged rats

Recent studies have demonstrated that aged rats are more susceptible to the lethal effects of endotoxin (ET) than young rats. The early (15 min to 7 h) hepatic ultrastructural and biochemical changes induced by ET in young (6 months) and aged (24 months) rats were evaluated to elucidate cell populations and/or the mechanisms that may be responsible for the previously observed differential effects. Aged rats given ET had significantly increased numbers of neutrophils in hepatic sinusoids at 30 min and thereafter as compared with ET-treated young rats. Morphologic evidence of coagulation within hepatic sinusoids, including aggregates of fibrin enmeshed among polymorphonuclear leukocytes and platelet aggregates, was frequently observed in ET-treated aged rats but not in ET-treated young rats. In contrast, Kupffer cells of ET-treated young rats frequently contained phagocytized neutrophils and platelets, whereas this phenomenon was rarely observed in Kupffer cells of ET-treated aged rats. Hepatocellular morphologic injury was more pronounced and occurred at earlier time periods in ET-treated aged rats, and was accompanied by significant increase in hepatic transaminases. ET-treated aged rats had an earlier onset and greater severity of endothelial cell injury than did ET-treated young rats. The results of this study indicate a greater aggregation of blood elements in the hepatic sinusoids of aged rats following the intravenous administration of ET, which suggests that a greater diminution in microcirculation was induced in aged rats by ET. Additionally, the increased phagocytosis of inflammatory cells by Kupffer cells of young rats may be a mechanism which affords protection against endotoxin-induced lethality.