Macro- and microscale variables regulate stent haemodynamics, fibrin deposition and thrombomodulin expression

Drug eluting stents are associated with late stent thrombosis (LST), delayed healing and prolonged exposure of stent struts to blood flow. Using macroscale disturbed and undisturbed fluid flow waveforms, we numerically and experimentally determined the effects of microscale model strut geometries up...

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Veröffentlicht in:Journal of the Royal Society interface 2014-05, Vol.11 (94), p.20131079-20131079
Hauptverfasser: Jiménez, Juan M., Prasad, Varesh, Yu, Michael D., Kampmeyer, Christopher P., Kaakour, Abdul-Hadi, Wang, Pei-Jiang, Maloney, Sean F., Wright, Nathan, Johnston, Ian, Jiang, Yi-Zhou, Davies, Peter F.
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container_end_page 20131079
container_issue 94
container_start_page 20131079
container_title Journal of the Royal Society interface
container_volume 11
creator Jiménez, Juan M.
Prasad, Varesh
Yu, Michael D.
Kampmeyer, Christopher P.
Kaakour, Abdul-Hadi
Wang, Pei-Jiang
Maloney, Sean F.
Wright, Nathan
Johnston, Ian
Jiang, Yi-Zhou
Davies, Peter F.
description Drug eluting stents are associated with late stent thrombosis (LST), delayed healing and prolonged exposure of stent struts to blood flow. Using macroscale disturbed and undisturbed fluid flow waveforms, we numerically and experimentally determined the effects of microscale model strut geometries upon the generation of prothrombotic conditions that are mediated by flow perturbations. Rectangular cross-sectional stent strut geometries of varying heights and corresponding streamlined versions were studied in the presence of disturbed and undisturbed bulk fluid flow. Numerical simulations and particle flow visualization experiments demonstrated that the interaction of bulk fluid flow and stent struts regulated the generation, size and dynamics of the peristrut flow recirculation zones. In the absence of endothelial cells, deposition of thrombin-generated fibrin occurred primarily in the recirculation zones. When endothelium was present, peristrut expression of anticoagulant thrombomodulin (TM) was dependent on strut height and geometry. Thinner and streamlined strut geometries reduced peristrut flow recirculation zones decreasing prothrombotic fibrin deposition and increasing endothelial anticoagulant TM expression. The studies define physical and functional consequences of macro- and microscale variables that relate to thrombogenicity associated with the most current stent designs, and particularly to LST.
doi_str_mv 10.1098/rsif.2013.1079
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When endothelium was present, peristrut expression of anticoagulant thrombomodulin (TM) was dependent on strut height and geometry. Thinner and streamlined strut geometries reduced peristrut flow recirculation zones decreasing prothrombotic fibrin deposition and increasing endothelial anticoagulant TM expression. 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subjects Cells, Cultured
Coronary Stent Thrombosis
Fibrin
Fibrin - metabolism
Gene Expression Regulation
Haemodynamics
Hemodynamics
Human Umbilical Vein Endothelial Cells - metabolism
Human Umbilical Vein Endothelial Cells - pathology
Humans
Models, Cardiovascular
Stent Geometry
Stent Streamlining
Stents
Thrombomodulin
Thrombomodulin - biosynthesis
Thrombosis - etiology
Thrombosis - metabolism
Thrombosis - pathology
title Macro- and microscale variables regulate stent haemodynamics, fibrin deposition and thrombomodulin expression
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