Sinusoidal circulatory disturbance by microthrombosis as a cause of endotoxin-induced hepatic injury.

The present study was undertaken in rats to examine the significance of sinusoidal circulatory disturbance by microthrombosis in the pathogenesis of hepatic damage and dysfunction due to endotoxin. Administration of endotoxin induced fibrin deposits and infiltration of polymorphonuclear leukocytes in the sinusoids, focal random coagulative hepatocellular necrosis and elevation of serum transaminase activities. When heparin was given simultaneously with endotoxin, the formation of fibrin thrombus in the sinusoids was prevented, and the endotoxin-induced morphological and functional changes in the liver were markedly inhibited. Infusion of thrombin into the portal vein induced a large amount of fibrin thrombi in the sinusoids, focal random necrotic foci resembling the lesions produced by endotoxin and elevation of levels of serum transaminases. These experimental data suggest that disturbance of hepatic microcirculation by sinusoidal thrombosis is the necessary and sufficient condition for the development of endotoxin-induced hepatic injury.