Blockade of platelet membrane glycoprotein Ib receptors delays intracoronary thrombogenesis, enhances thrombolysis, and delays coronary artery reocclusion in dogs

Sheng Kun Yao, Judy C. Ober, Leonard I. Garfinkel, Yocheved Hagay, Nathan Ezov, James J. Ferguson, H. Vernon Anderson, Amos Panet, Marian Gorecki, L. Maximilian Buja, James T. Willerson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

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 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.

Original languageEnglish
Pages (from-to)2822-2828
Number of pages7
JournalCirculation
Volume89
Issue number6
DOIs
StatePublished - Jun 1994
Externally publishedYes

Keywords

  • platelets
  • tissue plasminogen activator
  • von Willebrand factor

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