Yao S K, Ober J C, Garfinkel L I, Hagay Y, Ezov N, Ferguson J J, Anderson H V, Panet A, Gorecki M, Buja L M
Cardiovascular Research Laboratory, St Luke's Episcopal Hospital/Texas Heart Institute, Houston.
Circulation. 1994 Jun;89(6):2822-8. doi: 10.1161/01.cir.89.6.2822.
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.
血管性血友病因子与血小板膜糖蛋白Ib受体相互作用，介导狭窄和内皮损伤动脉中的血小板黏附和血栓形成。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是否会延迟或预防冠状动脉再闭塞。27只犬在冠状动脉电损伤诱导血栓形成前，分别接受生理盐水、VCL或阿司匹林治疗。与生理盐水组（18±3分钟）相比，VCL组（70±10分钟）和阿司匹林组（69±20分钟）从损伤到闭塞性血栓形成的时间显著延长（P<.001和P<.05）。另外选取30只犬诱导血栓形成，然后分四组接受溶栓治疗。我们的主要发现是，在用TPA（80微克/千克 + 8微克·千克⁻¹·分钟⁻¹）和肝素（200单位/千克）治疗后，72±11分钟发生冠状动脉再闭塞（n = 7）；在用TPA、肝素和VCL（4毫克/千克 + 2毫克·千克⁻¹·小时⁻¹）治疗后，142±24分钟发生冠状动脉再闭塞（n = 7）（与TPA和肝素组相比，P<.05）；在用TPA、肝素和阿司匹林（5毫克/千克）治疗后，74±13分钟发生冠状动脉再闭塞（n = 8）；在用TPA、肝素、VCL和阿司匹林治疗后，173±8分钟发生冠状动脉再闭塞（n = 8）（与TPA和肝素组相比，P<.001）。因此，VCL增加了冠状动脉血栓形成所需的时间，并且与TPA和肝素联合使用时，比阿司匹林更有效地延迟冠状动脉再闭塞。
