Beneficial effects of the prostacyclin analogue taprostene on cardiovascular, pulmonary and renal disturbances in endotoxin-shocked rabbits.

Abstract

The prostacyclin analogue taprostene protects against lethal endotoxemia in rats. In the present study, the effects of taprostene on endotoxin-induced cardiovascular, pulmonary and renal alterations have been investigated. In anesthetized rabbits, infusion of 0.5 mg/kg Escherichia coli lipopolysaccharide i.v. over 30 min produced systemic hypotension, pulmonary hypertension, and decreases in cardiac output, peripheral oxygen delivery and renal glomerular filtration rate. In endotoxemic rabbits treated with taprostene (0.2 micrograms.kg-1.min-1 i.v. over 180 min), the blood pressure tended to be lower than in untreated endotoxemic controls. Taprostene reduced the total peripheral resistance and abolished the endotoxin-induced increases in pulmonary artery pressure and resistance. Taprostene prevented the decreases in cardiac output and peripheral oxygen supply. At the end of the experiment the glomerular filtration rate was higher in taprostene-treated than in untreated endotoxemic rabbits and did not differ significantly from that in non-endotoxemic controls. The results show that taprostene prevents the pulmonary hypertension, preserves cardiac output and peripheral oxygen delivery, and substantially maintains the glomerular filtration rate in endotoxin-shocked rabbits.