Humoral factors may be responsible for the hyperdynamic circulation seen in portal hypertension. Endotoxin, a peripheral arteriolar vasodilator, has been proposed to mediate this hernodynamic picture. We examined the pathogenic role of endotoxin in portal vein-ligated rats, a prehepatic portal hypertensive model with a well-developed hyperdynamic circulation. To this end, we (a) administered oral neomycin, a poorly absorbable antibiotic, at doses of 50 and 100 mg/day for 7 days and found no evident splanchnic hernodynamic effects of a 2-log-fold reduction of cecal aerobic bacterial flora as assessed by the radioactive microsphere technique in portal vein-ligated rats studied in the postanesthesia awake state; (b) assayed endotoxin in arterial samples using a quantitative limulus assay and found no evidence of endotoxinemia in PVL rats; (c) induced a state of endotoxin tolerance by repeated daily intraperitoneal injections of lowdose endotoxin and found no amelioration of the hyperdynamic state in portal vein-ligated rats. Our results do not support the hypothesis that endotoxin playa a maor pathogenic role in the hyperdynamic circulation of this experimental model. (HEPATOLOGY 1w)0;12:1152-1156.)
A hyperdynamic circulation, characterized by peripheral arterial vasodilatation and a high cardiac output, is a feature of both acute ( 1 ) and chronic (2) liver disease. Its pathogenesis remains unclear. Earlier studies suggested a bypass effect of portal-systemic shunting (3) similar to the consequences of arteriovenous fistulas on the circulation. Recently (41, the onset of the hyperdynamic state has been dissociated from the development of portocollateral circulation in rats after partial portal vein ligation (PVL), a model of extensive portal-systemic shunting. Because blood from such animals may induce a decrease of splanchnic (5) and hindquarter (6) arteriolar resistance in normal rats,