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.

Flow shear stress differentially regulates endothelial uptake of nanocarriers targeted to distinct epitopes of PECAM-1

“…These differences potentially have profound implications for local transport rates at the endothelial surface, an element of obvious importance to NC delivery. Exploration of NC behavior in a high Re model of arterial flow using a large volume, pulsatile fast flow system [70] will investigate complex separations of flow (eddies, vortices) typical of athero-susceptible arterial sites [71] and is beyond the scope of the present report.…”

Late thrombotic events after bioresorbable scaffold implantation: a systematic review and meta-analysis of randomized clinical trials

“…Following implantation, the thick non-embedded strut may disrupt the laminar flow, create eddies with areas of reversal of the flow behind the struts that have shown to predispose to fibrin deposition and potentially DT. 30,31 These rheological alterations might be exacerbated by a relative high footprint of the scaffold seen in cases with device/vessel mismatch and under deployment. Several .5) 25 (25.5) 33 (34) 35 (31) 690 ( .1) 1 (1) 11 (14.1) 8 (10) 55 ( registries have shown that image-guided scaffold implantation is associated with good outcomes.…”

Lymph flow regulates collecting lymphatic vessel maturation in vivo

“…Recent studies have identified a number of genes that are specifically upregulated in developing lymphatic valves in vivo, including Prox1, Foxc2, Cx37, Itga9, and Gata2 (7, 9, 10, 12), as well as some -such as Lyve1 -that are downregulated in both valves (13) and mature collecting vessels (32). To directly investigate the role of fluid shear in directing these molecular events, we next tested the genetic response of human LECs to fluid shear forces designed to reproduce those in collecting lymphatic vessels using an in vitro parallel plate flow chamber and pulsatile flow system (33). Since the shear levels in the developing lymphatic network are still unknown, lymphatic flow was modeled according to actual shear stress and lymph flow values measured in adult rat mesenteric lymphatics.…”