Pumphrey C W, Fuster V, Dewanjee M K, Chesebro J H, Vlietstra R E, Kaye M P
Am J Cardiol. 1983 Feb;51(3):591-5. doi: 10.1016/s0002-9149(83)80102-7.
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 micrograms/kg/min perioperatively, 8 dogs received nifedipine 4 micrograms/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 less than 0.001). In addition, the estimated total platelet deposition along the graft was reduced in dogs treated with dipyridamole was reduced in dogs treated with dipyridamole (2,073.2 X 10(6)) (p less than 0.01), verapamil (1,898.9 X 10(6)) (p less than 0.001), and nifedipine (1,474.8 X 10(6)) (p less than 0.001) as compared with controls (3,056.2 X 10(6)). 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.
由于血小板活化与细胞内钙流量有关，维拉帕米和硝苯地平之类的钙拮抗剂药物可能具有有益的血小板抑制作用。因此，将这些药物的效果与已确定的血小板抑制剂双嘧达莫的效果进行了比较，观察其在杂种狗两侧股动脉植入的聚四氟乙烯（戈尔特斯）移植物中预防铟-111标记的自体血小板沉积和血栓形成的情况。8只狗在围手术期接受7.5微克/千克/分钟的维拉帕米，8只狗在围手术期接受4微克/千克/小时的硝苯地平，8只狗在手术前24小时内口服50毫克双嘧达莫，每日两次，16只对照狗在围手术期接受等渗盐溶液。灌注3小时后，接受双嘧达莫（465.1毫克）、维拉帕米（453.7毫克）或硝苯地平（389.7毫克）治疗的狗的移植物和腔内血栓的中位重量低于对照狗（680.2毫克）（p<0.001）。此外，与对照狗（3,056.2×10⁶）相比，接受双嘧达莫治疗的狗（2,073.2×10⁶）（p<0.01）、维拉帕米（1,898.9×10⁶）（p<0.001）和硝苯地平（1,474.8×10⁶）（p<0.001）沿移植物的估计总血小板沉积减少。当从14个移植物中取出壁血栓时，中位73%的血小板位于血栓与移植物之间的界面处。我们得出结论，在该模型中，所有3种药物均通过抑制血小板活性来预防血栓形成，且钙拮抗剂药物与双嘧达莫一样有效。
