Effect of Platelet Suppressants on Experimental Arterial Thrombosis

Abstract

A reproducible model of platelet rich thrombi was produced in canine arteries by a previously described technique of intravascular insertion of metal tubing. The effect of platelet suppressants including sulfinpyrazone and ticrynafen, a clofibrate analog, on the rate and nature of thrombus formation was studied. ADP and epinephrine induced platelet aggregation of the animal's platelet rich plasma was monitored during the experiment. Platelet aggregation was impaired after the intravenous administration of either sulfinpyrazone (30 mg/kg body weight) or ticrynafen (100 mg/kg body weight). The rate of thrombus formation was not significantly altered by sulfinpyrazone when compared to the control, but histochemically, the thrombus studied showed a greatly diminished platelet content. In contrast, ticrynafen was able to prevent a complete occlusion of the involved vascular segment and a weak thrombus composed mostly of fibrin was produced instead. This effect of ticrynafen was dose related with minimal changes observed at a dose of 75 mg/kg. The results suggest that this arterial thrombosis model is of value in evaluating antithrombotic agents. They also indicate a potential value of ticrynafen as a therapeutic agent which should be further studied.