INCREASED SHEAR-STRESS OVERCOMES THE ANTITHROMBOTIC PLATELET INHIBITORY EFFECT OF ASPIRIN IN STENOSED DOG CORONARY-ARTERIES

Background Shear stress is one of the known platelet activating mechan isms that leads to thrombosis. Increased shear stress has also been po stulated to reverse the antithrombotic effect of some drugs such as as pirin (ASA). Methods and Results Experiments were conducted in five do gs to determine the minimal shear stress levels that produce acute pla telet thrombus formation in mechanically stenosed arteries and the inc rease in shear required to reverse the antithrombotic effect of ASA. A fter intimal and medial damage, stenosis was produced in the circumfle x coronary artery. We used the finite-difference numerical solution of the Navier-Stokes equation to determine the wall shear stresses in th e area of stenosis. At 70+/-6% coronary diameter reduction, cyclic flo w reductions (CFRs) caused by acute platelet thrombus formation were o bserved in the stenosed lumen. At this level of stenosis, the shear st ress was 144+/-15 Pa. ASA given at a dose of 5 mg/kg IV inhibited in v ivo acute platelet-mediated thrombus formation and abolished CFRs in a ll dogs. However, increasing the stenosis level to 80+/-5% caused the CFRs to return. The shear stress increased with the increased level of stenosis to 226+/-22 Pa. Thus, an average 10% increase in diameter na rrowing caused a 56+/-20% increase in shear stress (P<.005) and renewe d platelet activation and thrombus formation despite ASA pretreatment. Conclusions Individuals who take ASA daily to prevent coronary artery thrombus formation may not be well protected when a change in hemodyn amics, such as an acute hypertensive episode, or an increase in stenos is severity due to a ruptured atherosclerotic plaque causes an increas e in shear stress.