Quantifying the effects of shear stress and shear exposure duration regulation on flow induced platelet activation and aggregation

Abstract

A heightened flow shear stress magnitude or increased exposure duration at any shear stress magnitude enhances platelet activation. It has been suggested that increased circulating activated platelets are an indication of enhanced cardiovascular risk and that activated platelets can perpetuate cardiovascular diseases. However, the combined effects that shear stress and shear exposure duration have on platelet activation and aggregation are not clear. Our objective was to identify a new parameter ("shear stress-exposure time") to predict platelet functional changes better than the absolute magnitude of shear stress. Platelets were exposed to shear stress waveforms, with different combinations of shear stress magnitude and exposure duration, in a circulation flow loop. Timed samples were removed from the flow loop to quantify thrombogenicity (modified prothrombinase assay), aggregation potential (optical platelet aggregometry), and cell surface marker expression (flow cytometry). Flow induced platelet activation and aggregation was enhanced with increased shear stress-exposure time. Platelets that were exposed to waveforms with the same shear stress-exposure time had the same thrombogenicity and aggregation potential. This was true even for waveforms that exposed platelets to shear stress magnitudes varying from 4 to 40 dynes/cm(2). These results indicate that shear stress-exposure time is a good predictor of platelet activation and aggregation levels and it may be able to predict the likelihood of cardiovascular disease onset.