Enhanced hepatotoxicity of endotoxin by hypoxia.

Pathogenesis of hepatic injury often seen in patients with congestive heart failure is obscure, but hepatic hypoxia and endotoxaemia resulting from congestive heart failure may relate to it. The present study was undertaken in rats to ascertain whether hepatic hypoxia potentiates endotoxin-induced hepatotoxicity. Hypoxic condition of hepatocytes ws induced by exposure to 7% oxygen for 3 hours or administration of ethanol. When endotoxin was given immediately before or several hours after hypoxia, elevation of activities of serum transaminases and focal random hepatocellular necrosis in the lobules were induced, although these functional and morphological changes were not observed in rats with hypoxia or endotoxaemia alone. This finding indicates that hepatic hypoxia leads to a potentiation of sensitivity to endotoxin hepatotoxicity which persists for several hours after recovery from hypoxia. Moreover, these experimental data suggest that hepatic injury in patients with congestive heart failure may be caused by enhancement of endotoxin hepatotoxicity by hepatic hypoxia.