Device thrombogenicity emulation: A novel methodology for optimizing the thromboresistance of cardiovascular devices

JOURNAL OF BIOMECHANICS

卷:46

Article

Bluestein, Danny¹  Einav, Shmuel^1,5  Slepian, Marvin J.^1,2,3,4 

[1] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA

[2] Univ Arizona, Dept Med, Tucson, AZ USA

[3] Univ Arizona, Dept Biomed Engn, Tucson, AZ USA

[4] Univ Arizona, Sarver Heart Ctr, Tucson, AZ USA

[5] Tel Aviv Univ, Dept Biomed Engn, Fac Engn, IL-69978 Tel Aviv, Israel

关键词: Mechanical circulatory support (MCS);    Ventricular assist devices (VAD);    Thrombogenicity;    Blood flow;    Platelets;    Device optimization;    Device thrombogenicity emulation (DTE);   

DOI  :  10.1016/j.jbiomech.2012.11.033

来源: Elsevier

【 摘 要 】

Thrombotic complications with mechanical circulatory support (MCS) devices remain a critical limitation to their long-term use. Device-induced shear forces may enhance the thrombotic potential of MCS devices through chronic activation of platelets, with a known dose-time response of the platelets to the accumulated stress experienced while flowing through the device-mandating complex, lifelong anticoagulation therapy. To enhance the thromboresistance of these devices for facilitating their long-term use, a universal predictive methodology entitled device thrombogenicity emulation (DTE) was developed. DTE is aimed at optimizing the thromboresistance of any MCS device. It is designed to test device-mediated thrombogenicity, coupled with virtual design modifications, in an iterative approach. This disruptive technology combines in silico numerical simulations with in vitro measurements, by correlating device hemodynamics with platelet activity coagulation markers-before and after iterative design modifications aimed at achieving optimized thrombogenic performance. The design changes are first tested in the numerical domain, and the resultant device conditions are then emulated in a hemodynamic shearing device (HSD) in which platelet activity is measured under device emulated conditions. As such, DTE can be easily incorporated during the device research and development phase-achieving minimization of the device thrombogenicity before prototypes are built and tested thereby reducing the ultimate cost of preclinical and clinical trials. The robust capability of this predictive technology is demonstrated here in various MCS devices. The presented examples indicate the potential of DTE for reducing device thrombogenicity to a level that may obviate or significantly reduce the extent of anticoagulation currently mandated for patients implanted with MCS devices for safe long-term clinical use. (C) 2012 Elsevier Ltd. All rights reserved.

【 授权许可】

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