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 mechanisms that leads to thrombosis. Increased shear stress has also been postulated to reverse the antithrombotic effect of some drugs such as aspirin (ASA).


RESULTS
Experiments were conducted in five dogs to determine the minimal shear stress levels that produce acute platelet thrombus formation in mechanically stenosed arteries and the increase in shear required to reverse the antithrombotic effect of ASA. After intimal and medial damage, stenosis was produced in the circumflex coronary artery. We used the finite-difference numerical solution of the Navier-Stokes equation to determine the wall shear stresses in the area of stenosis. At 70+/-6% coronary diameter reduction, cyclic flow reductions (CFRs) caused by acute platelet thrombus formation were observed in the stenosed lumen. At this level of stenosis, the shear stress was 144+/-15 Pa. ASA given at a dose of 5 mg/kg IV inhibited in vivo acute platelet-mediated thrombus formation and abolished CFRs in all 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 narrowing caused a 56+/-20% increase in shear stress (P<.005) and renewed 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 hemodynamics, such as an acute hypertensive episode, or an increase in stenosis severity due a ruptured atherosclerotic plaque causes an increase in shear stress.
Maalej
N
N
Cardiology Section, University of Wisconsin-Madison, WI 53792 USA.
Folts
J D
JD
D000818:Animals; D001241:Aspirin / Q000627:therapeutic use*; D003327:Coronary Disease / Q000503:physiopathology / Q000517:prevention & control*; D004285:Dogs; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D013314:Stress, Mechanical
D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D001241:Aspirin