title: Blockade of platelet membrane glycoprotein Ib receptors delays intracoronary thrombogenesis, enhances thrombolysis, and delays coronary artery reocclusion in dogs.
abstract: 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.
authors.affiliation: Cardiovascular Research Laboratory, St Luke's Episcopal Hospital/Texas Heart Institute, Houston.
authors.forename: S K
authors.initials: SK
authors.lastname: Yao
authors.forename: J C
authors.initials: JC
authors.lastname: Ober
authors.forename: L I
authors.initials: LI
authors.lastname: Garfinkel
authors.forename: Y
authors.initials: Y
authors.lastname: Hagay
authors.forename: N
authors.initials: N
authors.lastname: Ezov
authors.forename: J J
authors.initials: JJ
authors.lastname: Ferguson
authors.forename: H V
authors.initials: HV
authors.lastname: Anderson
authors.forename: A
authors.initials: A
authors.lastname: Panet
authors.forename: M
authors.initials: M
authors.lastname: Gorecki
authors.forename: L M
authors.initials: LM
authors.lastname: Buja
mesh_terms: D000818:Animals; D003328:Coronary Thrombosis / Q000517:prevention & control*; D004285:Dogs; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006493:Heparin / Q000627:therapeutic use; D010446:Peptide Fragments / Q000627:therapeutic use*; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D014841:von Willebrand Factor / Q000627:therapeutic use*
chemical_list: D005343:Fibrinolytic Agents; D010446:Peptide Fragments; D010980:Platelet Membrane Glycoproteins; D011994:Recombinant Proteins; D014841:von Willebrand Factor; D006493:Heparin; D010959:Tissue Plasminogen Activator