TY - JOUR
T1 - Blockade of platelet membrane glycoprotein Ib receptors delays intracoronary thrombogenesis, enhances thrombolysis, and delays coronary artery reocclusion in dogs
AU - Yao, Sheng Kun
AU - Ober, Judy C.
AU - Garfinkel, Leonard I.
AU - Hagay, Yocheved
AU - Ezov, Nathan
AU - Ferguson, James J.
AU - Anderson, H. Vernon
AU - Panet, Amos
AU - Gorecki, Marian
AU - Buja, L. Maximilian
AU - Willerson, James T.
PY - 1994/6
Y1 - 1994/6
N2 - 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 Willebrand 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 μg/kg + 8 μg · 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.
AB - 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 Willebrand 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 μg/kg + 8 μg · 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.
KW - platelets
KW - tissue plasminogen activator
KW - von Willebrand factor
UR - http://www.scopus.com/inward/record.url?scp=0028240844&partnerID=8YFLogxK
U2 - 10.1161/01.CIR.89.6.2822
DO - 10.1161/01.CIR.89.6.2822
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C2 - 8205697
AN - SCOPUS:0028240844
SN - 0009-7322
VL - 89
SP - 2822
EP - 2828
JO - Circulation
JF - Circulation
IS - 6
ER -