MORPHOLOGICAL AND FUNCTIONAL ALTERATIONS TO SINUSOIDAL ENDOTHELIAL-CELLS IN THE EARLY PHASE OF ENDOTOXIN-INDUCED LIVER-FAILURE AFTER PARTIAL-HEPATECTOMY IN RATS

Liver failure following major hepatectomy is characterized pathologica lly by massive hepatic necrosis, which is thought to begin with injury of sinusoidal endothelial cells (SECs). To examine the early events o f SECs leading to hepatic damage, we performed time-course analyses of the morphological and functional perturbation of SECs after endotoxin administration to hepatectomized rats. At 1.5 h after endotoxin injec tion, when hepatocellular damage was not yet evident, SECs showed augm ented expression of intercellular adhesion molecule-1, with frequent a dherence of infiltrating leucocytes and ultrastructural features of de fenestration and hypertrophied cytoplasm enriched with cell organelles . The serum level of hyaluronate, as an indicator of the functional st ate of SECs, was significantly elevated. At 3 h, SECs underwent necros is and disruption, accompanied by fibrin deposits with concomitant hep atocellular necrosis. The morphological and functional alterations of SECs precede necrotic changes in hepatocytes and SECs in endotoxin-ind uced liver failure after partial hepatectomy.