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.