Ketanserin prevents platelet aggregation and endotoxin-induced pulmonary vasoconstriction.

Pulmonary hypertension secondary to sepsis is due, in part, to release of serotonin from platelets. This study examines the effects of ketanserin, a new, highly specific serotonin antagonist, on platelet aggregation and the cardiovascular changes associated with bacterial endotoxemia in dogs. Ketanserin markedly inhibits in vitro platelet aggregation induced by mixing serotonin and epinephrine. When ketanserin is administered to animals before endotoxin infusion, cardiac output is greater and mean pulmonary artery pressure (MPAP), pulmonary and systemic vascular resistance (PVR and SVR) and arteriovenous oxygen content difference [C(a-v)O2] are less than in animals not receiving ketanserin. Similar results for PVR, SVR, and C(a-v)O2 are obtained when ketanserin is administered after endotoxin infusion. The data indicate that ketanserin inhibits serotonin-induced platelet aggregation and modifies many cardiovascular changes associated with bacterial endotoxemia.