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

Abstract

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.

Thrombin Is a Distal Mediator of Lipopolysaccharide-Induced Liver Injury in the Rat

“…In rats, infusion of thrombin into the por-24]. In the rat, circulating plasma fibrinogen concentra-tal vein induces damage similar to that observed after tion falls dramatically after intravenous injection of administration of LPS [13], and antithrombin III atten-LPS [2,8], and there is morphologic evidence of fibrin uates the effects of LPS [28]. The observations that deposition within the liver sinusoids [12,25].…”

“…Because one of the LPS-induced changes is results indicate that thrombin is a critical and distal deposition of fibrin in the microvasculature of the liver mediator of LPS-induced liver damage and contributes [12], it has been hypothesized that occlusion of the microto hepatocellular injury through a mechanism that is circulation by insoluble fibrin clots and consequent ischindependent of clot formation. Furthermore, inflamma-emia are responsible for the liver necrosis [13,14]. Recent tory events triggered by LPS exposure are a prerequisite results, however, have raised doubts about this theory.…”

In vivo studies of endotoxin removal by lysine–cellulose adsorbents

“…Studies have shown that endotoxemia is a common complication of multi organ failure (MOF) and ET are believed to be strongly associated with the pathogenesis of acute liver damage in a variety of experimental models [29,30]. Therefore, the evaluation of clinical liver function tests can provide information about the effect of hemoperfusion on sepsis treatment.…”

In vitro and in vivo expression of inducible nitric oxide synthase during experimental endotoxemia: Involvement of other cytokines

“…Liver injury caused by in vivo LPS administration is thought partly because extremely swollen Kupffer cells, platelet aggregation, and granulocytes obstruct the sinusoids, and result in liver tissue damage [Shibayama., 1987;Van et al, 1988]. By the light microscopy and electron microscopy findings, the hypothesis has been established on the basis of these structural analysis.…”