SUMMARY 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 (15 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.Endotoxaemia is of increasing interest in the pathogenesis of acute hepatic failure and its complications. It is proposed that endotoxins coming from the intestine are insufficiently cleared from the portal venous system because of an impairment of the reticuloendothelial system. Endotoxins may then be responsible for both the intravascular coagulation and renal failure which are part of the picture of acute liver failure (Wilkinson, Gazzard, Arroyo, Moodie, and Williams, 1974). Gans, Mori, Lindsey, Kaster, Richter, Quinlan, Dineen, and Tan (1971) discussed these problems in connexion with their experiments concerning the anhepatic dog and suggested from the results that bacteria from the intestine or their products, no longer adequately eliminated by the liver reticuloendothelial system, are contributing significantly toward the pathogenesis of hepatic failure.

Bei den trizyklischen Antidepressiva oder Thymo(ana)leptika handelt es sich um Pharmaka, die eine spezielle antidepressive sowie psychomotorisch aktivierende Wirkung aufweisen und bei denen der neuroleptische Effekt in den Hintergrund tritt. Die Thymoleptika, die für unsere Betrachtung von Interesse sind, gehören neben den Monoaminoxidase-Hemmern zur Gruppe der Antidepressiva. Chemisch können diese Verbindungen vom Chiorpromazin abgeleitet werden (Abbildung 1), das seit 1952 in der psychiatrischen Therapie verwendet wird. Dabei wurden entweder die Substituenten oder der Kern der Phenothiazine so verändert, daß Substanzen mit anderer therapeutischer Breite oder gar mit anderen Indikationen entstanden. Die trizyklischen Thymoleptika umfassen im wesentlichen die in Tabelle 1 aufgeführten Gruppen (64). I CH3 (CH2 )3-N 1CH3 In, ipram in I CH3 (CH2)3 N '"CH3 Chiorpromazin H CH CH (CH2)2 N ( 'CH3

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