Blockade of platelet membrane glycoprotein Ib receptors delays intracoronary thrombogenesis, enhances thrombolysis, and delays coronary artery reocclusion in dogs.
Blockade of platelet membrane glycoprotein Ib receptors delays intracoronary thrombogenesis, enhances thrombolysis, and delays coronary artery reocclusion in dogs.
复制标题
阻断血小板膜糖蛋白 Ib 受体可延迟狗冠状动脉内血栓形成、增强血栓溶解并延迟冠状动脉再闭塞。
DOI：
10.1161/01.cir.89.6.2822
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发表时间：
1994
期刊：
影响因子：
37.8
通讯作者：
Buja,LM
中科院分区：
文献类型：
--
作者：
Yao,SK;Ober,JC;Garfinkel,LI;Hagay,Y;Ezov,N;Ferguson,JJ;Anderson,HV;Panet,A;Gorecki,M;Buja,LM
血管性血友病因子和血小板膜糖蛋白Ib受体相互作用介导狭窄和内皮损伤动脉中的血小板粘附和血栓形成。我们希望确定用重组血管性血友病因子结合域（VCL）阻断糖蛋白Ib受体是否会增加冠状动脉损伤后血栓形成所需的时间。我们还希望确定在用组织纤溶酶原激活剂（TPA）溶栓后，VCL是否能延迟或防止冠状动脉再闭塞。27只犬在通过电损伤诱导冠状动脉血栓形成之前接受生理盐水、VCL或阿司匹林治疗。从损伤到闭塞性血栓形成的时间，VCL组（70 ± 10分钟）和阿司匹林组（69 ± 20分钟）明显长于生理盐水组（18 ± 3分钟，P <0.001和P <0.05）。在其他30只狗中诱导血栓形成，然后分四组接受溶栓治疗。我们的主要发现是TPA治疗后72 ± 11分钟发生冠状动脉再闭塞（80 μ g/kg + 8 μ g.kg-1.min-1）和肝素（200 U/kg）（n = 7）; TPA、肝素和VCL后142 +/- 24分钟（4 mg/kg + 2 mg.kg-1.h-1）（n = 7）（与TPA和肝素相比，P <0.05）; TPA后74 +/-13分钟，肝素和阿司匹林（5 mg/kg）（n = 8）; TPA、肝素、VCL和阿司匹林（n = 8）后173 ± 8分钟（与TPA和肝素相比，P <0.001）。因此，VCL增加了冠状动脉血栓形成所需的时间长度，并且当与TPA和肝素一起使用时，比阿司匹林更有效地延迟冠状动脉再闭塞。
Von Willebrand factor and platelet membrane glycoprotein Ib receptors interact to mediate platelet adhesion and thrombogenesis in stenosed and endothelium-injured arteries. We wished to determine whether blocking glycoprotein Ib receptors with a recombinant von Willibrand factor binding domain (VCL) increases the time required for thrombus formation after injury to the coronary arteries. We also wished to determine whether, after thrombolysis with tissue plasminogen activator (TPA), VCL delays or protects against coronary artery reocclusion. Twenty-seven dogs were treated with either saline, VCL, or aspirin before thrombosis was induced in their coronary arteries by electrical injury. The time from injury to the formation of occlusive thrombi was significantly greater with VCL (70 +/- 10 minutes) and aspirin (69 +/- 20 minutes) than with saline (18 +/- 3 minutes, P < .001 and P < .05). Thrombosis was induced in 30 other dogs that then received thrombolytic treatment in four groups. Our major finding was that coronary artery reocclusion occurred in 72 +/- 11 minutes after treatment with TPA (80 micrograms/kg + 8 micrograms.kg-1.min-1) and heparin (200 U/kg) (n = 7); in 142 +/- 24 minutes after TPA, heparin, and VCL (4 mg/kg + 2 mg.kg-1.h-1) (n = 7) (compared with TPA and heparin, P < .05); in 74 +/- 13 minutes after TPA, heparin, and aspirin (5 mg/kg) (n = 8); and in 173 +/- 8 minutes after TPA, heparin, VCL, and aspirin (n = 8) (compared with TPA and heparin, P < .001). Thus, VCL increases the length of time required for thrombus formation in coronary arteries, and, when given with TPA and heparin, delays coronary artery reocclusion more effectively than aspirin.