Pathogenesis of focal and random hepatocellular necrosis in endotoxemia: microscopic observation <i>in vivo</i>

The present study was undertaken in rats to clarify the role of sinusoidal circulatory disturbances due to fibrin thrombi in the development of focal and random hepatocellular necrosis in endotoxemia. Sinusoidal circulation was examined microscopically in vivo in rats injected with endotoxin or heparin, or both. The sinusoids in places were occluded by adherent fibrin and neutrophils soon after endotoxin injection, and subsequently the sinusoidal blood flow stagnated, reversed, or detoured. Most of these sinusoidal circulatory disturbances recovered in a few hours. However, when the sinusoidal occlusion developed simultaneously in clusters of adjacent sinusoids, the sinusoidal circulatory disturbance persisted and induced ischemic foci and then hepatocellular coagulative necrosis. Pretreatment with heparin definitely prevented the adherence of fibrin and neutrophils to the sinusoidal walls, and focal hepatocellular necrosis did not appear. These results suggest that focal and random hepatocellular necrosis in endotoxemia is caused by circulatory disturbances due to fibrin thrombi in clusters of adjacent sinusoids.