Harker L A, Hanson S R
J Clin Invest. 1979 Aug;64(2):559-60. doi: 10.1172/JCI109494.
A quantitative primate model of arterial thromboembolism has been characterized with respect to mechanism and usefulness in evaluating modifying variables. The model involved the kinetic measurements of (51)Cr-platelets and (125)I-fibrinogen consumption by femoral arteriovenous cannulae in chaired baboons. Cannula platelet consumption correlated directly with exposed cannular area for irradiated Silastic and polyurethane (correlation coefficients of 0.940 and 0.901, respectively; P < 0.001) and remained steady state for months. Nonirradiated Silastic was only minimally reactive with platelets. Despite increased rates of platelet consumption circulating fibrinogen was not measurably destroyed by any of the cannulae tested. Cannula platelet consumption was independent of cannula flow rate, platelet count, heparin anti-coagulation, and ancrod defibrinogenation.(111)In-platelet imaging of irradiated Silastic cannulae demonstrated luminal accumulation and subsequent embolization of irregular platelet masses. When irradiated Silastic cannulae were inserted as extension segments in the renal arteries of four animals the glomerular vessels became progressively occluded with nonfibrin-containing platelet thromboemboli. Nonirradiated Silastic cannulae in control arteries produced no significant vascular occlusion. Because the survival of platelets from animals with consumptive cannulae was not shortened in normal recipient animals we concluded that platelets were either irreversibly removed through thromboembolic consumption or unaffected in their viability. Oral administration of dipyridamole and sulfinpyrazone decreased cannula platelet consumption in a dose-dependent manner with complete interruption at 20 and 250 mumol/kg body wt per d (in three divided doses), respectively, whereas oral acetylsalicylic acid (10-330 mumol/kg per d) had no measurable effect on cannula platelet consumption. We conclude that this primate model simulates arterial thrombotic processes in man and that this model is suitable for the in vivo evaluation of biomaterials and of drugs that modify platelet behavior.
一种定量的动脉血栓栓塞灵长类动物模型已根据其在评估调节变量方面的机制和实用性进行了表征。该模型涉及在端坐的狒狒中通过股动静脉插管对（51）铬标记血小板和（125）碘标记纤维蛋白原消耗的动力学测量。插管血小板消耗与照射过的硅橡胶和聚氨酯的暴露插管面积直接相关（相关系数分别为0.940和0.901；P<0.001），并且数月保持稳定状态。未照射的硅橡胶与血小板的反应性极低。尽管血小板消耗率增加，但循环纤维蛋白原未被任何测试插管显著破坏。插管血小板消耗与插管流速、血小板计数、肝素抗凝和安克洛酶去纤维蛋白作用无关。（111）铟标记血小板对照射过的硅橡胶插管成像显示管腔内有不规则血小板团块积聚并随后发生栓塞。当将照射过的硅橡胶插管作为延长段插入四只动物的肾动脉中时，肾小球血管逐渐被不含纤维蛋白的血小板血栓栓塞阻塞。对照动脉中未照射的硅橡胶插管未产生明显的血管阻塞。由于来自使用消耗性插管动物的血小板在正常受体动物中的存活时间未缩短，我们得出结论，血小板要么通过血栓栓塞消耗被不可逆地清除，要么其活力未受影响。口服双嘧达莫和磺吡酮以剂量依赖方式降低插管血小板消耗，分别在每日每千克体重20和250微摩尔（分三次给药）时完全阻断，而口服乙酰水杨酸（每日每千克体重10 - 330微摩尔）对插管血小板消耗无明显影响。我们得出结论，该灵长类动物模型模拟了人类的动脉血栓形成过程，并且该模型适用于体内评估生物材料和改变血小板行为的药物。
