Comparison of the antithrombotic action of calcium antagonist drugs with dipyridamole in dogs

Because platelet activation is associated with fluxes of intracellular calcium, calcium antagonist drugs such as verapamil and nifedipine may have useful platelet inhibitor effects. Accordingly, the effect of these drugs was compared with that of dipyridamole, an established platelet inhibitor, in preventing the deposition of indium-111-labeled autologous platelets and thrombus development in polytetrafluoroethylene (Gore-Tex®) grafts interposed in both femoral arteries in mongrel dogs. Eight dogs received verapamil 7.5 μg/kg/min perioperatively, 8 dogs received nifedipine 4 μg/kg/h perioperatively, 8 dogs received dipyridamole 50 mg orally given twice during the 24 hours before operation, and 16 control dogs received isotonic saline solution perioperatively. After 3 hours of perfusion, the median weight of the grafts and luminal thrombus was less in dogs treated with dipyridamole (465.1 mg), verapamil (453.7 mg), or nifedipine (389.7 mg) than in control dogs (680.2 mg) (p <0.001). In addition, the estimated total platelet deposition along the graft was reduced in dogs treated with dipyridamole (2,073.2 ×10⁶) (p <0.01), verapamil (1,898.9 × 10⁶) (p <0.001), and nifedipine (1,474.8 × 10⁶) (p <0.001) as compared with controls (3,056.2 × 10⁶). When the mural thrombus was removed from 14 grafts, a median 73% of the platelets were located in the interface between thrombus and graft. We conclude that all 3 drugs prevent thrombus formation by inhibiting platelet activity in this model, and that the calcium antagonist drugs are as effective as dipyridamole.