Effect of Shear Stress on Acute Platelet Thrombus Formation in Canine Stenosed Carotid Arteries: An In Vivo Quantitative Study.

Abstract

We investigated the in vivo effect of percent stenosis, trans-stenotic pressure, and shear stress (SS) on platelet accumulation (PA) in canine mechanically injured and stenosed carotid arteries. In 10 dogs, intimal damage and controlled variations in stenosis were produced on the carotid artery. Blood flow through the stenosis, trans-stenotic pressure, and stenosis geometry were measured. A NaI gamma detector was collimated and placed over the stenosis to detect gamma rays emitted by autologous radiolabeled platelets as they accumulated inside the stenosis. The SS was obtained from the finite difference solution of the Navier-Stokes equations. As the flow declined during thrombus formation, the radioactive count accumulated in an inverse fashion. The rate of flow decline directly correlated with the rate of PA during thrombus formation (r(2) > 0.9). Compared with the undamaged and unstenosed artery, the PA increased by 52 +/- 34% due to mild stenosis (40-60%). PA increased by 94 +/- 66% due to severe stenosis (60-70%) and by 145 +/- 56% due to critical stenosis (70-80%; P > 0.01). The platelet accumulation produced totally occlusive thrombus formation at levels of stenosis higher than 70 +/- 5% (diameter narrowing), and for trans-stenotic pressure gradients higher than 50 +/- 5 mmHg producing SS greater than 100 +/- 10 Pa. The PA was maximum at the stenotic portion of the vessel where the level of SS is the highest (P < 0.001). In vivo platelet-mediated thrombosis increases with SS and occurs at the stenotic portion of the stenosis where the SS is the highest. Severe stenoses produce critical levels of SS that potentiate thrombosis and lead to life-threatening arterial occlusion.