Endotoxin and the hyperdynamic circulation of portal vein-ligated rats

Humoral factors may be responsible for the hyperdynamic circulation seen in portal hypertension. Endotoxin, a peripheral arteriolar vasodilator, has been proposed to mediate this hemodynamic 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 hemodynamic 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 low-dose endotoxin and found no amelioration of the hyperdynamic state in portal vein-ligated rats. Our results do not support the hypothesis that endotoxin plays a major pathogenic role in the hyperdynamic circulation of this experimental model.