A new in vivo model of arterial thrombosis: The effect of administration of ticlopidine and verapamil in dogs

Abstract

An in vivo model of arterial thrombosis was developed in which either polytetrafluoroethylene (PTFE [Gore-Tex]) or autologous vein grafts were used to replace a segment of the femoral arteries of dogs. In one series of studies, 5 cm of PTFE and 5 cm of autologous femoral vein were used in each animal and blood flow was resumed for 1 hour. 111In-labeled autologous platelets accumulated in greater amounts on the PTFE grafts (93.6 × 10 6 platelets/cm) than on the vein grafts (2.6 × 10 6 platelets/cm) (P<0.001). Orally administered ticlopidine (30 mg/kg/day for 2 days), an established inhibitor of platelets, reduced platelet deposition on the PTFE grafts to 10.5 × 10 6 platelets/cm (P<0.01). In a second series of studies, PTFE grafts were interposed on both sides in each animal, and blood flow was resumed for 3 hours. With intravenously administered verapamil, a calcium antagonist, given perioperatively at 7.5 ug/kg/min, 12 of 16 grafts in eight dogs were patent compared with only 2 of 16 grafts in eight control dogs ( P <0.001). Furthermore, platelet deposition on the grafts was reduced from 1,090 × 10 6 platelets/cm to 303 × 10 6 platelets/cm ( P <0.001). Thus, both ticlopidine and verapamil are effective antithrombotic agents as a result of their inhibition of platelet activity in this model, and these results provide further evidence of a central role for calcium in platelet activation.