Analysis Of The Effect Of Component Elements Of Hemodynamic Shear Stress Profiles On Shear-Mediated Platelet Activation In Cardiovascular Implantable Therapeutic Devices

Study: Hemodynamic shear stress (HSS) exerted by cardiovascular blood recirculating devices (BRDs) impacts platelets inducing altered biochemical signaling and activation, which may ultimately lead to thrombosis. A clear identification of the dominant characteristics of the HSS patterns responsible for shear-mediated platelet activation (SMPA) has not yet been fully accomplished. Methods: Experimental signal frequency content analysis was applied to HSS waveforms characteristics of a prosthetic heart valve (Fig. 1A) to sistematically analyze the relative contributions of component elements as to overall SMPA. Extracted frequency waveforms (from low- to high-frequency components, Fig. 1A,B), as well as the original stress curves, composed of the full range of frequency components (Fig. 1A,B), were programmed into a computer-controlled Hemodynamic Shearing Device to stimulate platelets. The Platelet Activity State (PAS) assay was utilized to quantify the associated dynamics of SMPA. Results: We demonstrated that high frequency oscillations are the major determinants for priming, triggering and yielding activated prothrombotic behavior for stimulated platelets, even if the imparted HSS has low magnitude and brief exposure time (Fig. 1C). Conversely, the low frequency components of the stress signal, with limited oscillations over time, did not induce significant activation, despite being of high magnitude and-or exposure time (Fig. 1C). With this study we provide a more fundamental understanding for the mechanobiological responsiveness of circulating platelets to the hemodynamic environment of BRDs, and the importance of these environments in mediating life-threatening thrombotic complications associated with SMPA. Our data provide translational insights to guide future technological improvements aimed at optimizing the thromboresistance of cardiovascular therapeutic BRDs.