BLOCKADE OF PLATELET MEMBRANE GLYCOPROTEIN IN RECEPTORS DELAYS INTRACORONARY THROMBOGENESIS, ENHANCES THROMBOLYSIS, AND DELAYS CORONARY-ARTERY REOCCLUSION IN DOGS

Von Willebrand factor and platelet membrane glycoprotein Ib receptors interact to mediate platelet adhesion and thrombogenesis in stenosed a nd endothelium-injured arteries. We wished to determine whether blocki ng glycoprotein Ib receptors with a recombinant von Willebrand factor binding domain (VCL) increases the time required for thrombus formatio n after injury to the coronary arteries. We also wished to determine w hether, after thrombolysis with tissue plasminogen activator (TPA), VC L delays or protects against coronary artery reocclusion. Twenty-seven dogs were treated with either saline, VCL, or aspirin before thrombos is was induced in their coronary arteries by electrical injury. The ti me 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 induce d in 30 other dogs that then received thrombolytic treatment in four g roups. Our major finding was that coronary artery reocclusion occurred in 72+/-11 minutes after treatment with TPA (80 mu g/kg+8 mu g . 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-') (n=7) (compared wi th 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, V CL, and aspirin (n=8) (compared with TPA and heparin, P<.001). Thus, V CL increases the length of time required for thrombus formation in cor onary arteries, and, when given with TPA and heparin, delays coronary artery reocclusion more effectively than aspirin.