Pumphrey C W, Fuster V, Dewanjee M K, Murphy K P, Vlietstra R E, Kaye M P
Thromb Res. 1982 Dec 1;28(5):663-75. doi: 10.1016/0049-3848(82)90157-8.
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 X 10(6) platelets/cm) than on the vein grafts (2.6 X 10(6) platelets/cm) (P less than 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 X 10(6) platelets/cm (P less than 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 less than 0.001). Furthermore, platelet deposition on the grafts was reduced from 1,090 X 10(6) platelets/cm to 303 X 10(6) platelets/cm (P less than 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.
构建了一种动脉血栓形成的体内模型，其中使用聚四氟乙烯（PTFE [戈尔特斯]）或自体静脉移植物来替代犬股动脉的一段血管。在一系列研究中，每只动物使用5厘米的PTFE和5厘米的自体股静脉，恢复血流1小时。与静脉移植物（2.6×10⁶个血小板/厘米）相比，¹¹¹In标记的自体血小板在PTFE移植物上积累的量更多（93.6×10⁶个血小板/厘米）（P<0.001）。口服噻氯匹定（30毫克/千克/天，共2天），一种已证实的血小板抑制剂，可将PTFE移植物上的血小板沉积减少至10.5×10⁶个血小板/厘米（P<0.01）。在第二项研究系列中，在每只动物的两侧均植入PTFE移植物，并恢复血流3小时。通过在围手术期以7.5微克/千克/分钟的速度静脉注射钙拮抗剂维拉帕米，八只犬的16个移植物中有12个保持通畅，而八只对照犬的16个移植物中只有2个保持通畅（P<0.001）。此外，移植物上的血小板沉积从1090×10⁶个血小板/厘米减少至303×10⁶个血小板/厘米（P<0.001）。因此，噻氯匹定和维拉帕米在该模型中由于抑制血小板活性均为有效的抗血栓形成药物，并且这些结果进一步证明了钙在血小板激活中起核心作用。
