Effect of shear stress on acute thrombus formation in stenosed dog carotid arteries

Shear induced activation of platelets plays a major role in platelet adhesion and aggregation at atherosclerotic lesions. We investigated the effect of shear stress (SS - tangential force/area), in vivo, on platelet accumulation (PA) in canine stenosed carotid arteries (SCA), in 10 dogs. A carotid artery/jugular vein anastomotic shunt was produced. Medial damage and controlled increments in stenosis (measured with arteriograms) were produced on the artery. Blood flow and the pressure gradient across the SCA were measured. The wall SS at the SCA was obtained from the finite difference solution of the Navier-Stokes equations. Autologous platelets were labeled with In-111 Oxine and injected IV. A Nal gamma detector collimated over the SCA, detected radio-labeled PA as platelet mediated thrombi form in the SCA. The PA increased after medial damage to 129±25% compared to the control undamaged and unstenosed artery. PA increased to 152±54% compared to control with mild stenosis (40-60% diameter narrowing). PA increased to 194166% with critical stenosis (60-70%), and to 245±56% with stenosis > 70%. The PA produced totally occlusive thrombi at levels of stenosis higher than 70±5% producing trans-stenou'c pressure gradients higher than 500 mmHg. Totally occlusive thrombus formation was only produced by SS greater than 100±10 Pa. The PA was maximum at the narrowest portion of SCA where the SS is the highest. At sites of atherosclerotic lesions, an increase in trans-stenotic pressure due to hypertensive episode or a sudden increase in stenosis due to plaque rupture can produce critical levels of SS that may produce acute occlusive thrombus formation leading to stroke or myocardial infarction. Supported by the UW Grad School.