Protective effect of ticlopidine on thrombotic obstruction of an experimental arterio-venous shunt in rats

Abstract

A polyethylene tubing was installed between the right carotid artery and the jugular vein of the rat to make a loop-shaped arterio-venous shunt. In most of the rats, the vascular shunt was obstructed by white thrombi together with blood clot within 4 hours after installation of the vascular shunt.Oral administration of ticlopidine at doses above 5mg/kg markedly prevented the shunt obstruction through strong inhibition of platelet aggregation by this agent. In the ticlopidine-treated rats, only small numbers of single platelets scattered on the inner surface of the shunt were observed.On the other hand, acetylsalicylic acid did not show any antithrombotic effect in this vascular shunt model, despite of its inhibitory action on collagen-induced platelet aggregation. Such ineffectiveness of acetylsalicylic acid seems to be probably related to almost complete inhibition of PGI2 generation in the carotid artery by this agent.Dipyridamole did not exert any effect on platelet aggregation at doses ranging from 10 to 300mg/kg, but increased the generation of PGI2-like activity in the vascular tissue in a dose-dependent manner. This effect of dipyridamole, however, was too short in duration to give a significant antithrombotic effect in the present shunt model, although a tendency to prevent shunt obstruction was observed only at an extremely high oral dose or frequently repeated intraperitoneal doses of this agent.