Effects of CI-930 on hemostasis, thrombosis, and AA-induced hemodynamic reaction.

In mice, CI-930 0.5-2 mg.kg-1 ip not only prolonged the tail bleeding time but also protected the mice from sudden thromboembolic death induced by arachidonic acid (AA, 100 mg.kg-1, i.v.) or TXA2/PGH2 mimetic U46619 (200 micrograms.kg-1, i.v.). CI-930 0.625 and 2.5 mg.kg-1 i.v. exhibited a dose-dependent inhibitory effect on thrombus formation in rat arteriovenous shunt. All these effects of CI-930 were more potent than those of dazoxiben, a known antiplatelet drug. In rabbit, AA 0.75 mg.kg-1 i.v. caused a rapid and marked increase in pulmonary vascular resistance and a concomitant sharp decrease in cardiac output and carotid arterial pressure. CI-930 itself 0.5 mg.kg-1 i.v. resulted in a long-lasting fall in carotid arterial pressure, systemic vascular resistance, and a slight decrease in cardiac output. In addition, CI-930 protected rabbit from all the harmful hemodynamic responses to the occlusion of pulmonary microcirculation, which was induced by AA. The results suggest that CI-930 possess a potent anti-hemostatic, antithrombotic, and probably antihypertensive effects on experimental animals.