title: Macro- and microscale variables regulate stent haemodynamics, fibrin deposition and thrombomodulin expression.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, , Philadelphia, PA 19104, USA.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Jiménez
authors.forename: Varesh
authors.initials: V
authors.lastname: Prasad
authors.forename: Michael D
authors.initials: MD
authors.lastname: Yu
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Kampmeyer
authors.forename: Abdul-Hadi
authors.initials: AH
authors.lastname: Kaakour
authors.forename: Pei-Jiang
authors.initials: PJ
authors.lastname: Wang
authors.forename: Sean F
authors.initials: SF
authors.lastname: Maloney
authors.forename: Nathan
authors.initials: N
authors.lastname: Wright
authors.forename: Ian
authors.initials: I
authors.lastname: Johnston
authors.forename: Yi-Zhou
authors.initials: YZ
authors.lastname: Jiang
authors.forename: Peter F
authors.initials: PF
authors.lastname: Davies
mesh_terms: D002478:Cells, Cultured; D005337:Fibrin / Q000378:metabolism*; D005786:Gene Expression Regulation; D006439:Hemodynamics; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008955:Models, Cardiovascular; D015607:Stents; D018180:Thrombomodulin / Q000096:biosynthesis*; D013927:Thrombosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
chemical_list: C546931:THBD protein, human; D018180:Thrombomodulin; D005337:Fibrin
keywords: coronary stent thrombosis; fibrin; haemodynamics; stent geometry; stent streamlining; thrombomodulin