High Frequency Components of Hemodynamic Shear Stress Profiles are a Major Determinant of Shear-Mediated Platelet Activation in Therapeutic Blood Recirculating Devices
Slepian, Marvin J.
Fiore, Gianfranco B.
AffiliationUniv Arizona, Sarver Heart Ctr, Dept Med & Biomed Engn
MetadataShow full item record
PublisherNATURE PUBLISHING GROUP
CitationHigh Frequency Components of Hemodynamic Shear Stress Profiles are a Major Determinant of Shear-Mediated Platelet Activation in Therapeutic Blood Recirculating Devices 2017, 7 (1) Scientific Reports
Rights© The Author(s) 2017. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License.
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AbstractWe systematically analyzed the relative contributions of frequency component elements of hemodynamic shear stress waveforms encountered in cardiovascular blood recirculating devices as to overall platelet activation over time. 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 shear stress has low magnitude and brief exposure time. 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. In vitro data were compared with numerical predictions computed according to a recently proposed numerical model of shear-mediated platelet activation. The numerical model effectively resolved the correlation between platelet activation and the various frequency components examined. However, numerical predictions exhibited a different activation trend compared to experimental results for different time points of a stress activation sequence. With this study we provide a more fundamental understanding for the mechanobiological responsiveness of circulating platelets to the hemodynamic environment of cardiovascular devices, and the importance of these environments in mediating life-threatening thromboembolic complications associated with shear-mediated platelet activation. Experimental data will guide further optimization of the thromboresistance of cardiovascular implantable therapeutic devices.
VersionFinal published version
SponsorsCARIPLO Foundation [2015-1044]; Regione Lombardia and CARIPLO Foundation [2016-0901]; NIH/NIBIB [5U01EB012487]