Aurintricarboxylic acid in a canine model of coronary artery thrombosis.
Aurintricarboxylic acid in a canine model of coronary artery thrombosis.
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金精三羧酸在犬冠状动脉血栓形成模型中的作用。
DOI：
10.1161/01.cir.81.3.1106
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发表时间：
1990
期刊：
影响因子：
37.8
通讯作者：
Adelman,B
中科院分区：
文献类型：
--
作者：
Strony,J;Phillips,M;Brands,D;Moake,J;Adelman,B
血小板血栓形成发生在严重动脉狭窄的地方，在那里剪应力升高。剪切应力似乎通过启动血管性血友病因子与血小板糖蛋白Ib的结合来诱导血小板聚集。最近的体外研究表明，金羧酸可以抑制剪切应力诱导的血小板聚集。这种作用是通过金羧酸结合血管性血友病因子介导的；这种结合导致血管性血友病因子与糖蛋白Ib相互作用的抑制。在本研究中，我们在犬冠状动脉狭窄模型中检测了金羧酸对血小板依赖性循环血流减少（CFRs）的影响。在剂量反应实验中，6只动物先给药4 mg/kg金羧酸，然后每10分钟给药1 mg/kg金羧酸。6.7 mg/kg金三羧酸对所有动物的CFRs均有抑制作用；血栓素A2类似物U46619不能重新启动CFRs。持续输注肾上腺素（0.4微克/千克/分钟）导致CFRs复发；然而，3.7 mg/kg的额外金三羧酸再次诱导CFRs的完全抑制。另外，5只动物给药10 mg/kg金三羧酸，对CFRs有完全抑制作用。收缩血管狭窄的平均面积为83%，收缩部位的剪应力平均为350 dynes/cm2。金羧酸不改变血流动力学、凝血酶时间、血小板计数或ADP/肾上腺素诱导的血小板聚集。这些数据表明，血小板糖蛋白-血管性血友病因子相互作用在冠状动脉闭塞期间是重要的，金羧酸可以抑制冠状动脉狭窄相关的冠状动脉血栓形成。
Platelet thrombus formation occurs at sites of severe arterial narrowing where shear stress is elevated. Shear stress appears to induce platelet aggregation in vitro by means of initiation of von Willebrand factor binding to platelet glycoprotein Ib. Recent in vitro studies have demonstrated that aurintricarboxylic acid can inhibit shear stress-induced platelet aggregation. This effect is mediated by aurintricarboxylic acid binding to von Willebrand factor; this binding results in inhibition of von Willebrand factor interaction with glycoprotein Ib. In this study, we examined the effect of aurintricarboxylic acid on platelet-dependent cyclic flow reductions (CFRs) in a canine coronary stenosis model. In dose-response experiments, six animals received 4 mg/kg aurintricarboxylic acid by bolus infusion, followed by 1 mg/kg every 10 minutes. Total inhibition of CFRs was observed in all animals after 6.7 mg/kg aurintricarboxylic acid; CFRs could not be reinitiated by the thromboxane A2 analogue U46619. Continuous infusion of epinephrine (0.4 micrograms/kg/min) caused CFRs to return; however, 3.7 mg/kg additional aurintricarboxylic acid again induced total inhibition of CFRs. In addition, five animals received a bolus infusion of 10 mg/kg aurintricarboxylic acid, which caused total inhibition of CFRs. The average area of stenosis in the constricted vessels was 83%, and shear stress at the site of constriction averaged 350 dynes/cm2. Aurintricarboxylic acid did not alter hemodynamics, thrombin time, platelet count, or ADP/epinephrine-induced platelet aggregation. These data indicate that platelet glycoprotein Ib-von Willebrand factor interactions are important during coronary occlusion and that aurintricarboxylic acid can inhibit coronary thrombosis associated with coronary constriction.