Effects of elapsed time on downstream platelet adhesion following transient exposure to elevated upstream shear forces

Abstract

Transient exposure to elevated shear forces is known to prime platelets for enhanced downstream adhesion, but how far downstream these priming effects persist is not known. In the present study, the platelet capture regions, prepared by immobilizing fibrinogen, collagen, or von Willebrand factor, were placed at three different distances from the upstream stenotic region to vary the elapsed time of circulating platelets downstream. Platelet adhesion increased with the increase of upstream wall shear rates from 1620 s−1 to 11,560 s−1 for all three downstream proteins, but only the adhesion to fibrinogen increased significantly with the distance between the upstream stenotic region and the downstream capture region. In contrast, platelet adhesion to downstream collagen remained essentially independent on the distance and the adhesion to von Willebrand factor marginally increased with the distance after transient platelet exposure to upstream wall shear rates of 2145 s−1 and 11,560 s−1. The results implied that the activation of fibrinogen receptor GPIIb/IIIa by transient exposure to high upstream wall shear rates progresses in a time-dependent manner during the downstream flow of platelets. The highly elevated upstream wall shear rate of 11,560 s−1 altered the morphology of many platelets adhered to downstream fibrinogen from their native ellipsoidal to spread circular form. The platelet shape analysis showed that longer periods of post-stenotic flow increased the surface coverage fraction of ellipsoidal platelet population and decreased the surface coverage fraction of fully spread platelets on fibrinogen for both transiently elevated upstream wall shear rates.