Antithrombotic effects of ticlopidine, acetylsalicylic acid and dipyridamole in vascular shunt model in rats

Abstract

Antithrombotic action of three platelet aggregation inhibitors was studied in a vascular shunt model of rats in which occlusive white thrombus was formed in most of animals within 4 hr after a loopshaped polyethylene cannula was installed between the carotid artery and jugular vein. We also measured platelet aggregation in plasma and PGI 2-like activity of the arterial segment from the rats treated with these agents. Ticlopidine significantly prevented the thrombus formation at oral doses above 5 mg/kg in approximate proportion to its inhibitory effect on platelet aggregation. Acetylsalicylic acid had no antithrombotic effect despite of its potent anti-platelet action but it blocked generation of PGI 2-like substance by the carotid artery. Dipyridamole did not inhibit platelet aggregation but apparently increased the generation of PGI 2-like activity, and it showed a tendency to prevent the shunt thrombosis at a high dose. Thus, the thrombus formation in this shunt model appears to be affected by PGI2-generation by the vascular tissue as wall as platelet function.