Arteriosclerosis, Vol 10, 367-371, Copyright © 1990 by American Heart Association

ARTICLES

Inhibition of thrombus formation in vivo by novel antiplatelet agent

UM Marzec, AB Kelly, SR Hanson, A Lasslo and LA Harker
Roon Research Center for Arteriosclerosis and Thrombosis, Scripps Clinic and Research Foundation, La Jolla, California.

The antithrombotic and antihemostatic effects of the novel antiplatelet compound, alpha, alpha'-bis[3-(N,N-diethylcarbamoyl)piperidino]-p- xylene dihydrobromide (GT-12), were investigated in a baboon model of platelet-dependent thrombosis under high flow conditions. In this model, segments of collagen-coated tubing and Dacron vascular graft were placed as thrombus-inducing extension devices in exteriorized femoral arteriovenous shunts. The deposition of 111In-labeled platelets was measured for each thrombogenic segment throughout 1 hour by using gamma camera imaging. In addition, the 125I-fibrin retained in the forming thrombus was measured. Intravenous infusion of GT-12 (100 mumol/kg, 63.3 mg/kg) over a 15-minute period before the insertion of the test segments prolonged the bleeding time from a baseline value of 4.4 +/- 0.4 min to 7.6 +/- 1.0 min (p = 0.036) and inhibited platelet aggregation ex vivo induced by adenosine diphosphate (ED50 4.7 +/- 0.9 to 10.3 +/- 2.2 microM; p less than 0.02) and collagen (ED50 2.0 +/- 0.4 to 8.0 +/- 2.4 micrograms/ml; p less than 0.05). Deposition of platelets and fibrin was decreased in concert by 30% (p less than 0.05) for vascular grafts and possibly collagen segments at the end of the 60- minute observation period. We conclude that GT-12 is antithrombotic for Dacron graft-induced thrombus formation in vivo.