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.

The livers of rats subjected to end-to-side portacaval anastomoses were studied 3 to 5 months postoperatively by in uiuo and electron microscopy. Compared with sham-operated controls, the livers of portacaval anastomoses animals contained dilated, tortuous networks of sinusoids. The velocity of blood flow in these vessels tended to be slower and more variable than controls, but always progressed toward the hepatic venules. Blood entered the sinusoids from portal venules and from arteriosinus twigs which terminated in the initial segments of some of the sinusoids at the periphery of the lobule. Together, the arteriosinus twigs and the short, initial segments of these sinusoids formed functional arterioportal anastomoses. These, in combination with the lack of portal venous inflow, resulted in retrograde blood flow in portal venules. Nevertheless, blood still flowed from these portal venules into the sinusoids unless the sinusoid was fed by an arteriosinus twig. In addition to these microcirculatory alterations, the number of Kupffer cells that phagocytized latex particles was less in the animals with portacaval anastomoses, as was the number of particles ingested by these cells. Scanning and transmission electron microscopy confirmed the paucity of Kupffer cells. Those seen appeared inactive since they were flattened, exhibited few microplicae and filopodia and contained few latex particles. The endothelial cells of the sinusoid lining were perforated by increased numbers of large fenestrae which may be a reflection of devated intrasinusoid pressures generated by the expanded arterialization of the sinusoid bed. The observed dilated sinusoid network interspersed by narrowed plates of hepatocytes is also consistent with this hypothesis. Finally, scattered nodular foci were observed which contained enlarged hepatocytes, narrow sinusoids, active Kupffer cells, and more normal rates of blood flow. Such sites may represent attempts by the liver to regenerate its normal architecture.Portacaval anastomosis (PCA) is performed selectively to relieve portal hypertension and bleeding esophageal varices in patients suffering from cirrhosis of the liver.Several studies have reported major changes in hepatic hemodynamics and reticulo-endothelial function in animals following PCA (1). To date, however, direct in vivo microscopic evaluation of the altered microvasculature and Kupffer cell function has not been reported for such animals. 'In addition, the ultrastructural changes in the sinusoid wall that occur under these conditions is not clear although the morphometric changes in the liver 3 weeks following PCA recently were reported by Muller and Schroder (2).As a result, the hepatic microvasculature and distribution of phagocytic Kupffer cells in rats subjected to PCA was investigated using high-resolution in vivo microscopic methods of McCuskey ( 3 , 4 ) and McCuskey et al. (5). Subsequently, these livers were studied by scanning electron microscopy (SEM) and transmission (TEM) electron microscopy. The results form the basis...

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