Rates of coronary restenosis after stent implantation vary with stent design. Recent evidence suggests that alterations in wall shear stress associated with different stent types and changes in local vessel geometry after implantation may account for this disparity. We tested the hypothesis that wall shear stress is altered in a three-dimensional computational fluid dynamics (CFD) model after coronary implantation of a 16 mm slotted-tube stent during simulations of resting blood flow and maximal vasodilation. Canine left anterior descending coronary artery blood flow velocity and interior diameter were used to construct CFD models and evaluate wall shear stress proximal and distal to and within the stented region. Channeling of adjacent blood layers due to stent geometry had a profound affect on wall shear stress. Stagnation zones were localized around stent struts. Minimum wall shear stress decreased by 77% in stented compared to unstented vessels. Regions of low wall shear stress were extended at the stent outlet and localized to regions where adjacent axial strut spacing was minimized and the circumferential distance between struts was greatest within the stent. The present results depict alterations in wall shear stress caused by a slotted-tube stent and support the hypothesis that stent geometry may be a risk factor for restenosis by affecting local wall shear stress distributions.

Restenosis limits the effectiveness of stents, but the mechanisms responsible for this phenomenon remain incompletely described. Stent geometry and expansion during deployment produce alterations in vascular anatomy that may adversely affect wall shear stress (WSS) and correlate with neointimal hyperplasia. These considerations have been neglected in previous computational fluid dynamics models of stent hemodynamics. Thus we tested the hypothesis that deployment diameter and stent strut properties (e.g., number, width, and thickness) influence indexes of WSS predicted with three-dimensional computational fluid dynamics. Simulations were based on canine coronary artery diameter measurements. Stent-to-artery ratios of 1.1 or 1.2:1 were modeled, and computational vessels containing four or eight struts of two widths (0.197 or 0.329 mm) and two thicknesses (0.096 or 0.056 mm) subjected to an inlet velocity of 0.105 m/s were examined. WSS and spatial WSS gradients were calculated and expressed as a percentage of the stent and vessel area. Reducing strut thickness caused regions subjected to low WSS (<5 dyn/cm(2)) to decrease by approximately 87%. Increasing the number of struts produced a 2.75-fold increase in exposure to low WSS. Reducing strut width also caused a modest increase in the area of the vessel experiencing low WSS. Use of a 1.2:1 deployment ratio increased exposure to low WSS by 12-fold compared with stents implanted in a 1.1:1 stent-to-vessel ratio. Thinner struts caused a modest reduction in the area of the vessel subjected to elevated WSS gradients, but values were similar for the other simulations. The results suggest that stent designs that reduce strut number and thickness are less likely to subject the vessel to distributions of WSS associated with neointimal hyperplasia.

The success of vascular stents in the restoration of blood flow is limited by restenosis. Recent data generated from computational fluid dynamics (CFD) models suggest that stent geometry may cause local alterations in wall shear stress (WSS) that have been associated with neointimal hyperplasia and subsequent restenosis. However, previous CFD studies have ignored histological evidence of vascular straightening between circumferential stent struts. We tested the hypothesis that consideration of stent-induced vascular deformation may more accurately predict alterations in indexes of WSS that may subsequently account for histological findings after stenting. We further tested the hypothesis that the severity of these alterations in WSS varies with the degree of vascular deformation after implantation. Steady-state and time-dependent simulations of three-dimensional CFD arteries based on canine coronary artery measurements of diameter and blood flow were conducted, and WSS and WSS gradients were calculated. Circumferential straightening introduced areas of high WSS between stent struts that were absent in stented vessels of circular cross section. The area of vessel exposed to low WSS was dependent on the degree of circumferential vascular deformation and axial location within the stent. Stents with four vs. eight struts increased the intrastrut area of low WSS in vessels, regardless of cross-sectional geometry. Elevated WSS gradients were also observed between struts in vessels with polygonal cross sections. The results obtained using three-dimensional CFD models suggest that changes in vascular geometry after stent implantation are important determinants of WSS distributions that may be associated with subsequent neointimal hyperplasia.

Coronary stents improve resting blood flow and flow reserve in the presence of stenoses, but the impact of these devices on fluid dynamics during profound vasodilation is largely unknown. We tested the hypothesis that stent implantation affects adenosine-induced alterations in coronary hemodynamics and wall shear stress in anesthetized dogs (n = 6) instrumented for measurement of left anterior descending coronary artery (LAD) blood flow, velocity, diameter, and radius of curvature. Indexes of fluid dynamics and shear stress were determined before and after placement of a slotted-tube stent in the absence and presence of an adenosine infusion (1.0 mg/min). Adenosine increased blood flow, Reynolds (Re) and Dean numbers (De), and regional and oscillatory shear stress concomitant with reductions in LAD vascular resistance and segmental compliance before stent implantation. Increases in LAD blood flow, Re, De, and indexes of shear stress were observed after stent deployment (P < 0.05). Stent implantation reduced LAD segmental compliance to zero and potentiated increases in segmental and coronary vascular resistance during adenosine. Adenosine-induced increases in coronary blood flow and reserve, Re, De, and regional and oscillatory shear stress were attenuated after the stent was implanted. The results indicate that stent implantation blunts alterations in fluid dynamics during coronary vasodilation in vivo.

Paclitaxel (PTx) is reported to have an nonuniform steady-state concentration profile in the arterial wall. We utilized epifluorescence microscopy to make precise measurements of fluorescently-labeled PTx (F-PTx) distribution through an in vitro tissue mimic which contained varying concentrations of fibrin, elastin, soybean oil, palmitic acid, and solid glass beads. As little as 0.5 mg/mL of elastin in agarose produced a 50% drop in the measured diffusion coefficient, while as much as 10 mg/mL of fibrin in agarose was required for the same reduction in rate of transport. Because no reduction in the measured diffusion coefficient was observed for solubilized, extracted elastin or unassembled elastin-like polypeptides, the effect was specific to elastic fibers that closely resembled the native elastin network. Collectively, this work identifies a potential source for the high degree of partitioning observed for PTx in native tissue and further develops an in vitro technique for exploring complex tissue-drug interactions.