Endotoxin-induced liver necrosis and intravascular coagulation in rats enhanced by portacaval collateral circulation.
The effects of intravenously administered endotoxin on the hepatic and systemic circulation as well as on the coagulation system were evaluated in normal rats (n = 26), in rats with experimental portal hypertension (n = 15), and in rats with portacaval anastomosis (n = 22). Endotoxin (1-5 mg/kg) in the normal rat leads to a prompt increase of transaminase activity and to a hyperdynamic circulation with a consequent increase in the total hepatic blood flow. In a later phase (6 h postoperatively) the hepatic artery dilated with a consequent hepatic arterial hyperperfusion. The coagulation system was affected with signs of consumption coagulopathy. In the rats with portal hypertension and portacaval collaterals as well as in those with portacaval anastomosis, the endotoxin injection resulted in acute liver necrosis within 12 to 15 hours. The hepatic artery became overdilated with a cardiac output fraction of 25% (normal 5-5%). Blood extravasates and thrombi, rich in fibrin, were detected in the liver. It is suggested that this exaggeration of the endotoxin effect was due to an impaired clearance function of the reticuloendothelial system, probably as consequence of portacaval collateral circulation. It is concluded that endotoxins (1) damage the liver even in a normal organism; (2) are potent to induce acute liver necrosis, if the reticuloendothelial system is altered; (3) have to be taken into consideration as contribution to the pathogenesis of acute as well as chronic liver diseases.
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001779:Blood Coagulation Factors / Q000032:analysis; D001786:Blood Glucose / Q000032:analysis; D001810:Blood Volume; D002302:Cardiac Output; D003097:Collateral Circulation; D004731:Endotoxins / Q000494:pharmacology*; D004903:Erythrocyte Aggregation / Q000209:etiology*; D005337:Fibrin / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D006975:Hypertension, Portal; D008099:Liver / Q000473:pathology; D008102:Liver Circulation; D008107:Liver Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D009336:Necrosis / Q000209:etiology / Q000473:pathology; D010587:Phagocytosis; D011167:Portacaval Shunt, Surgical; D051381:Rats; D012039:Regional Blood Flow; D013997:Time Factors
D001779:Blood Coagulation Factors; D001786:Blood Glucose; D004731:Endotoxins; D005337:Fibrin; D005340:Fibrinogen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin