SUMMARY

Atherothrombosis can induce acute myocardial infarction and stroke by progressive stenosis of a blood vessel lumen to full occlusion. The goal of this research is to determine what shear rates are pertinent to an occluding blood vessel, the rate of thrombus growth relative to wall shear rates, and to develop a predictive model for estimating length of time to thrombus occlusion for a given atherosclerotic lesion. Computational studies of severely stenotic idealized vessels were performed to investigate the wall shear rates that may exist. The study shows that maximum shear rates in severe short stenoses were found to exceed 250,000 1/s (9,500 dynes/cm2). We utilize an in vitro experiment consisting of blood flow through a collagen coated stenosis to study the rate of thrombus growth. Growth is monitored through light microscopy and a camera. Computational fluid dynamics are used to determine shear rates along the thrombus surface as it grows. We found a strong positive correlation between thrombus growth rates and shear rates up to 6,000 1/s after a log-log transformation (r=0.85, p<0.0001). Growth rates at pathologic shear rates were typically 2-4 times greater than for physiologic shear rates below 400 s-1. To determine whether transport or kinetic binding limits the rate of thrombus growth, a computational model of platelet transport was developed. The model allows for thrombus growth by occluding computational cells. We show that thrombus is transport rate-limited for shear rates below 6,000 1/s, while it is more likely to be kinetic rate-limited for higher shear rates. Predictions of occlusion times based on the model demonstrate that increases in stenosis severity results in decreased time to occlusion.