High-shear stress sensitizes platelets to subsequent low-shear conditions.
Individuals with mechanical heart valve implants are plagued by flow-induced thromboembolic complications, which are undoubtedly caused by platelet activation. Flow fields in or around the affected regions involve brief exposure to pathologically high-shear stresses on the order of 100 to 1000 dyne/cm(2). Although high shear is known to activate platelets directly, their subsequent behavior is not known. We hypothesize that the post-high-shear activation behavior of platelets is particularly relevant in understanding the increased thrombotic risk associated with blood-recirculating prosthetic cardiovascular devices. Purified platelets were exposed to brief (5-40 s) periods of high-shear stress, and then exposed to longer periods (15-60 min) of low shear. Their activation state was measured using a prothrombinase-based assay. Platelets briefly exposed to an initial high-shear stress (e.g., 60 dyne/cm(2) for 40 s) activate a little, but this study shows that they are now sensitized, and when exposed to subsequent low shear stress, they activate at least 20-fold faster than platelets not initially exposed to high shear. The results show that platelets in vitro exposed beyond a threshold of high-shear stress are primed for subsequent activation under normal cardiovascular circulation conditions, and they do not recover from the initial high-shear insult.
Department of Biomedical Engineering, T18-030 Health Sciences Center, Stony Brook University, Stony Brook, NY 11794-8181, USA.
Jawaad
J
Sheriff
Danny
D
Bluestein
Gaurav
G
Girdhar
Jolyon
J
Jesty
D001792:Blood Platelets / Q000166:cytology / Q000502:physiology*; D002478:Cells, Cultured; D003198:Computer Simulation; D005260:Female; D006801:Humans; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008955:Models, Cardiovascular; D015539:Platelet Activation / Q000502:physiology*; D033081:Shear Strength / Q000502:physiology; D013314:Stress, Mechanical; D055815:Young Adult