Prevention of reoccluding platelet-rich thrombi in canine femoral arteries with a novel peptide antagonist of platelet glycoprotein IIb/IIIa receptors.
Prevention of reoccluding platelet-rich thrombi in canine femoral arteries with a novel peptide antagonist of platelet glycoprotein IIb/IIIa receptors.
复制标题
使用血小板糖蛋白 IIb/IIIa 受体的新型肽拮抗剂预防犬股动脉中富含血小板的血栓再闭塞。
DOI：
10.1161/01.cir.80.6.1775
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发表时间：
1989
期刊：
影响因子：
37.8
通讯作者：
Abendschein,DR
中科院分区：
文献类型：
--
作者：
Haskel,EJ;Adams,SP;Feigen,LP;Saffitz,JE;Gorczynski,RJ;Sobel,BE;Abendschein,DR
动脉血栓形成的成分可能是决定药物在最初成功溶栓后如何有效预防再闭塞的决定因素。在这项研究中，再闭塞的血小板或纤维蛋白丰富的血栓描绘扫描电子显微镜选择性地产生在狗的股动脉与使用电诱导血管损伤或植入铜线，分别。静脉输注组织型纤溶酶原激活剂（1 mg/kg，持续30分钟）后，产生富血小板血栓的制剂中的初始血栓溶解频率低于产生富纤维蛋白血栓的制剂（24例中有19例溶解，18例中有18例溶解，p = 0.06）。在初始动脉再通的犬中，静脉输注精氨酸-甘氨酸-酒石酸-O-甲基酪氨酸酰胺（RGDY）（与纤维蛋白原竞争结合血小板糖蛋白IIb/IIIa受体）可在90分钟内防止6/6只犬因富血小板血栓复发引起的再闭塞;在7只盐水输注对照犬中有5只发生再闭塞（p = 0.02）。RGDY在预防富纤维蛋白血栓复发引起的再闭塞方面仅部分有效（6例中3例再闭塞，6例对照中5例再闭塞，p = 0.54）。在两种制剂中使用阿司匹林获得了相似的结果。至少98%的胶原诱导的离体血小板聚集被RGDY或阿司匹林抑制。然而，与阿司匹林相反，血小板功能在停用RGDY后1小时内恢复正常。因此，血小板或纤维蛋白掺入血栓的相对比例影响组织型纤溶酶原激活剂诱导血栓溶解和抗血小板剂预防再闭塞的功效。RGDY是一种有效的短效血小板聚集抑制剂，可有效防止血小板沉积占主导地位的条件下的再闭塞。
The composition of an evolving arterial thrombus may be a determinant of how effectively pharmacologic agents prevent reocclusion after initially successful thrombolysis. In this study, reoccluding platelet- or fibrin-rich thrombi as delineated by scanning electron microscopy were produced selectively in the femoral arteries of dogs with the use of electrically induced vascular injury or implantation of copper wire, respectively. Initial thrombolysis after intravenous infusion of tissue-type plasminogen activator (1 mg/kg over 30 minutes) was less frequent in the preparation producing platelet-rich thrombi than in that producing fibrin-rich thrombi (lysis in 19 of 24 versus 18 of 18, p = 0.06). In dogs with initial arterial recanalization, intravenous infusion of arginine-glycine-aspartate-O-methyltyrosine amide (RGDY), which competes with fibrinogen for binding to platelet glycoprotein IIb/IIIa receptors, prevented reocclusion caused by recurrence of platelet-rich thrombi in six of six dogs within 90 minutes; reocclusion occurred in five of seven saline-infused control dogs (p = 0.02). RGDY was only partially effective in preventing reocclusion caused by recurrence of fibrin-rich thrombi (reocclusion in three of six versus five of six controls, p = 0.54). Similar results were obtained with aspirin in both preparations. At least 98% of platelet aggregation induced ex vivo by collagen was inhibited by either RGDY or aspirin. In contrast with aspirin, however, platelet function returned to normal within 1 hour after discontinuation of RGDY. Thus, the relative proportions of platelets or fibrin incorporated into thrombi influence the efficacy of both tissue-type plasminogen activator for inducing thrombolysis and antiplatelet agents for preventing reocclusion. RGDY is a potent, short-acting inhibitor of platelet aggregation that effectively prevents reocclusion under conditions in which platelet deposition predominates.