Circulation, Vol 81, 1106-1114, Copyright © 1990 by American Heart Association
J Strony, M Phillips, D Brands, J Moake and B Adelman
Platelet thrombus formation occurs at sites of severe arterial narrowing
where shear stress is elevated. Shear stress appears to induce platelet
aggregation in vitro by means of initiation of von Willebrand factor
binding to platelet glycoprotein Ib. Recent in vitro studies have
demonstrated that aurintricarboxylic acid can inhibit shear stress-induced
platelet aggregation. This effect is mediated by aurintricarboxylic acid
binding to von Willebrand factor; this binding results in inhibition of von
Willebrand factor interaction with glycoprotein Ib. In this study, we
examined the effect of aurintricarboxylic acid on platelet-dependent cyclic
flow reductions (CFRs) in a canine coronary stenosis model. In
dose-response experiments, six animals received 4 mg/kg aurintricarboxylic
acid by bolus infusion, followed by 1 mg/kg every 10 minutes. Total
inhibition of CFRs was observed in all animals after 6.7 mg/kg
aurintricarboxylic acid; CFRs could not be reinitiated by the thromboxane
A2 analogue U46619. Continuous infusion of epinephrine (0.4
micrograms/kg/min) caused CFRs to return; however, 3.7 mg/kg additional
aurintricarboxylic acid again induced total inhibition of CFRs. In
addition, five animals received a bolus infusion of 10 mg/kg
aurintricarboxylic acid, which caused total inhibition of CFRs. The average
area of stenosis in the constricted vessels was 83%, and shear stress at
the site of constriction averaged 350 dynes/cm2. Aurintricarboxylic acid
did not alter hemodynamics, thrombin time, platelet count, or
ADP/epinephrine- induced platelet aggregation. These data indicate that
platelet glycoprotein Ib-von Willebrand factor interactions are important
during coronary occlusion and that aurintricarboxylic acid can inhibit
coronary thrombosis associated with coronary constriction.
ARTICLES
Aurintricarboxylic acid in a canine model of coronary artery thrombosis
Hunter Holmes McGuire Veterans Administration Medical Center, Medical College of Virginia, Richmond 23249.
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