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Journal of Biomechanics 41 (2008) 10531061 www.elsevier.com/locate/jbiomech www.JBiomech.com

Effects of different stent designs on local hemodynamics in stented arteries

Rossella Balossino, Francesca Gervaso, Francesco Migliavacca, Gabriele Dubini
Laboratory of Biological Structure Mechanics, Department of Structural Engineering, Politecnico di Milano, Piazza Leonardo da Vinci, 32, 20133 Milan, Italy Accepted 3 December 2007

Abstract Following the deployment of a coronary stent and disruption of an atheromatous plaque, the deformation of the arterial wall and the presence of the stent struts create a new uid dynamic eld, which can cause an abnormal biological response. In this study 3D computational models were used to analyze the uid dynamic disturbances induced by the placement of a stent inside a coronary artery. Stents models were rst expanded against a simplied arterial plaque, with a solid mechanics analysis, and then subjected to a uid ow simulation under pulsatile physiological conditions. Spatial and temporal distribution of arterial wall shear stress (WSS) was investigated after the expansion of stents of different designs and different strut thicknesses. Common oscillatory WSS behavior was detected in all stent models. Comparing stent and vessel wall surfaces, maximum WSS values (in the order of 1 Pa) were located on the stent surface area. WSS spatial distribution on the vascular wall surface showed decreasing values from the center of the vessel wall portion delimited by the stent struts to the wall regions close to the struts. The hemodynamic effects induced by two different thickness values for the same stent design were investigated, too, and a reduced extension of low WSS region (o0.5 Pa) was observed for the model with a thicker strut. r 2007 Elsevier Ltd. All rights reserved.
Keywords: Stent; Computational uid dynamic; Wall shear stress; Numerical modeling

Introduction Many forms of vascular arterial disease can affect the ow of blood through arteries near or farther away from the heart. Coronary arteries are the most subjected ones to atherosclerosis, the end result of atheromatous plaques accumulation within the walls of the arteries. In case of partial or total lumen obstruction, a medical intervention is mandatory to restore the normal blood ow and avoid further complications. Stenting shows some advantages compared to other possible treatments, as it does not require any surgical operation and has less complications, pain and a more rapid recovery (Mullany, 2003). Since the rst implantation of stents in humans in 1986, many improvements, changes and discoveries have occurred to make them safer and more functional. The
Corresponding author. Tel.: +39 02 2399 4283; fax: +39 02 2399 4286.

E-mail address: rossella.balossino@polimi.it (R. Balossino). 0021-9290/$ - see front matter r 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.jbiomech.2007.12.005

presence of a non-biological device inside an artery causes an inevitable inammation response and inuences the uid dynamic behavior in the regions next to the arterial wall. Parts of the stent struts protruding into the lumen may induce the formation of vortices and stagnation zones which affect wall shear stress (WSS) spatial and temporal distribution. These effects depend on the stent conguration, its global length, the delivery system, the struts dimension, shape, spacing and many others (Tominaga et al., 1992; Rogers and Edelman, 1995). Moreover, lowmean shear stress, oscillating shear stress, high particleresidence times, and non-laminar ow have all been shown to occur in the locations where early intimal thickening is the greatest (Ku et al., 1985; Jin et al., 2004; LaDisa et al., 2005; Katritsis et al., 2007). In particular, a correlation exists between low-WSS values less than 0.5 Pa (Ku, 1997; Henry, 2000), sites of intimal thickening and non-uniform spatial distribution, which appear to represent important initiating factors for the development

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of atherosclerosis. Conversely, moderate and high WSS do not seem to contribute to neointima hyperplasia (Malek et al., 1999; Ku, 1997; LaDisa et al., 2004). In vivo and in vitro studies have revealed that stent structure inuences restenosis and thrombus formation between struts (Tominaga et al., 1992; Rogers and Edelman, 1995; Kleinstreuer et al., 2001). The evaluation of uid dynamic effects caused by stent geometric parameters is thus important to optimize the stent design. Computational uid dynamic (CFD) techniques have the advantage of a greater exibility and easiness of using with respect to the experimental or in vivo methods. They can provide detailed information on critical local ow parameters near the stent struts and the arterial wall, at least during the acute stage of the implantation. Many computational studies in the literature dealt with the inuence of stent physical parameters on uid dynamic changes correlated with the restenosis process (Henry, 2000; LaDisa et al., 2004; Berry et al., 2000). Stent strut spacing, thickness and number of struts were found to inuence the distribution of low and high shear stress values (Wentzel et al., 2001). LaDisa et al. (2003 and 2004) studied the localized alterations in coronary WSS by performing different CFD studies on 3D stent geometries with different struts number, width and thickness. The highest WSS values were found over the surface of the stent, decreasing modestly with subsequent struts. Lower values were instead detected before and after each stent strut and at transition between the vessel and the stent. Most studies considered the artery as a simple symmetrical and cylindrical model, neglecting the circumferential vascular deformation after stent implantation that alters the WSS distribution. A rst attempt to consider this effect was done by LaDisa et al. (2005) by comparing two 3D models of vessel and stent. The artery had a circular cross-section in the former whereas it was conformed to the stent geometry in the latter, thus resulting polygonal or straightened shape. Circumferential straightening introduced areas of high WSS among stent struts that were absent in the stented vessel model with circular crosssection. Stent prole or strut height was found to signicantly inuence neo-intimal thickness (Barth et al., 1996). Sullivan et al. (2002) compared a Clemson stent with a Palmaz one and showed that the former, due to its thicker struts, creates a 1020% greater degree of intimal thickening for the same degree of vessel injury. The new generation stents showed a less regular design compared to old stents (e.g. PalmazSchatz) with multiple links that provide higher exibility and consequently a lower chance to be perfectly symmetric after their expansion (Isenbarger and Resar, 2005). The novelty of the present study resides in the numerical simulation of the expansion of models resembling a number of commercially available stents inside a vessel in the presence of an atherosclerotic plaque. A solid mechanic analysis was combined with a uid dynamic one. A preliminary step was performed in which the stent was expanded against a stenosed artery, and then the deformed

conguration was used to carry out uid dynamic simulations. The basic idea was to compare different stent models in a conguration as close as possible to the real-life one. By varying the stent design or strut thickness and keeping the same boundary conditions, stents models were compared to suggest possible technical prescriptions to improve their performances.
Methods
Four different coronary stent designs were taken into consideration. They resemble four commercial intravascular stents: PalmazSchatz (Johnson & Johnson Interventional System, Warren, NJ, USA), Cordis BX Velocity (Johnson & Johnson Interventional System, Warren, NJ, USA), Sorin Carbostent (Sorin Biomedica S.p.A., Saluggia (VC), Italy) and Jostent Flex (JOMED AB, Helsingborg, Sweden). The four models will be referred to as STENT A, STENT B, STENT C and STENT D for Cordis BX velocity, Jostent ex, Sorin Carbostent and PalmazSchatz, respectively. The internal diameter, thickness, length and the number of struts of the simulated models are reported in Table 1. Apart from the PalmazSchatz, the other designs are considered new generation stents as their structures incorporate the presence of tubular-like rings and bridging members (links). Fig. 1 depicts the four stent models in their unexpanded conguration and the single unit used in the numerical simulations. Actually, a stent is pre-crimped in order to be mounted on the balloon catheter, so the unexpanded conguration refers to the congurations immediately before the crimping process. To obtain the dimensions of the models, the stents were analyzed by means of a Nikon SMZ800 stereo microscope (Nikon Corporation, Tokyo, Japan) when they were available, otherwise the models were constructed on the basis of images and data available in the literature (Serruys and Kutryk, 2000). Plaque and artery were modelled as simple, coaxial, hollow cylinders (Fig. 2a). The former (inner) is shorter and has rounded extremities; the latter has a length of 11.68 mm, an internal diameter of 2.15 mm, which becomes 3 mm after a pressurization of 100 mmHg, and a thickness of 0.5 mm. The plaque is a symmetric plaque with a length of 3.68 mm, an internal diameter of 1.25 mm, which becomes 1.46 mm after a pressurization of 100 mmHg, and a thickness of 0.45 mm. It corresponds after pressurization to a stenosis of 76% in terms of area reduction in the central cross-section. The methodology adopted to simulate the expansion of each stent inside the artery is described in a previous work (Migliavacca et al., 2007). Briey, the stent expansion was simulated with large deformation analyses by means of the commercial code ABAQUS (Abaqus Inc., Pawtucket, RI, USA) based on the nite element method. The mechanical behavior of both artery and plaque was described with hyperelastic isotropic constitutive models. The outer cross-sections of the artery were constrained in the longitudinal direction to simulate the fact that the considered model is not a stand-alone segment, but is part of a whole coronary artery. Furthermore, three nodes forming the vertices of an equilateral triangle were constrained in the tangential direction in an axial section located in the center of the artery, to avoid the rotation of the structure. These conditions allowed the radial expansion of the artery. Table 1 Main geometrical characteristics of the stent models Models Dint(mm) Thickness (mm) 0.15 0.05 0.075 0.1 Length (mm) 13 16 16 16 Strut number 6 10 10

STENT STENT STENT STENT

A B C D

0.9 1 0.95 1

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R. Balossino et al. / Journal of Biomechanics 41 (2008) 10531061 1055 With regard to the stent, boundary conditions were applied which constrain the three nodes forming the vertices of an equilateral triangle in the medial cross-section of the stent in the longitudinal and tangential directions. A single unit of stent, covering the entire stenosis length, was expanded under displacement control until a diameter of 3 mm was reached (Fig. 2b). Once the deformed congurations of artery, plaque and stent were obtained, the uid domain geometry delimited by the internal arterial and stent surfaces, was created using Rhinoceros 2.0 Evaluation CAD program (McNeel & Associates, Indianapolis, IN, USA). Each deployed conguration was imported into the CAD program as a point cloud and then the surfaces and the volumes were rebuilt (Fig. 2c). Since the stent was discretized using shell elements in the solid mechanic analysis, a thickness was prescribed for the stent according to the data reported in Table 1 to take into account the actual protrusion of the stent struts into the lumen. The geometry was then imported into the commercial code Gambit (ANSYS Inc., Canonsburg, PA, USA) to enable the mesh generation for the uid domain. A mixed grid was created by means of tetrahedral elements for the stented portion of the model and brick elements for the unstented one. A very ne discretization was prescribed in the region of interest, which is the stent imprint and the arterial wall within the stent struts (Fig. 2d), to guarantee an accurate evaluation of the signicant quantities. In the unstented portion a coarser mesh was generated (Fig. 2e). A grid-sensitivity analysis was conducted on six different meshes with increasing number of elements (102,540, 130,700, 203,200, 325,000, 654,000, and 689,000, respectively). The area weighted average WSS was calculated separately over the stent imprint and the vessel region around the stent struts. The values were compared according to the relative error, calculated as: y
2 1=2 1 s2 s2 2 sn 1 , x n1

Fig. 1. Stents models (left) and particular of the single stent units (right) used in the simulations.

where s is the standard deviation, n is the number of the different considered meshes and x is the WSS arithmetic mean. The relative errors were below the 5% for each mesh and the last three meshes showed no signicant differences in spite of the considerable increase in cell number. The choice was for the mesh with 654,000 cells and 160,000 nodes.

Fig. 2. 3D CAD geometry of the plaque and the artery (a); deformed conguration after stent expansion (b); uid domain (c); particular of the ne discretization in the vessel area within the stent struts (d) and of the coarser mesh in the area outside the stented region.

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1056 R. Balossino et al. / Journal of Biomechanics 41 (2008) 10531061 The ow simulations were carried out by numerically solving the continuity and NavierStokes momentum equations for a pulsatile blood ow, using the commercial package Fluent (ANSYS Inc., Canonsburg, PA, USA), based on the nite volume method. A three-dimensional double-precision, segregated and laminar solver was used with rst-order time implicit scheme employed to discretize the governing equations. Under-relaxation factors of 0.3 for pressure, 1 for density, and 0.7 for momentum were used. Standard discretization was followed for pressure with a PISO algorithm chosen for pressure-velocity coupling. A secondorder upwind scheme was adopted for the discretization of momentum. Convergence criterion for continuity and velocity residuals was kept at 104, an order of magnitude lower than the recommended value. The adopted inlet blood-ow velocity waveform was taken from the literature (LaDisa et al., 2005), which was obtained from a canine coronary artery under normal resting conditions and the data were sampled obtaining a nal step function. A time-varying velocity boundary condition with a parabolic prole was imposed at the inlet with a userdened subroutine (with a Womersley number equal to 2.87). A no-slip condition was specied on the wall which makes all velocity components equal to zero. The arterial wall was specied as rigid, a reasonable assumption in the stented portion even though questionable in the other parts of the domain. At the outlet, a zero-gauge pressure boundary condition was specied. Four cardiac cycles were simulated to guarantee a stable solution and the results referred to the last cycle.

Results The WSS results are reported with reference to the luminal side of the strut surface (stent area) and to the luminal side of the bare vascular wall surface (vessel area). Fig. 3 illustrates the stent area (a) and the vessel area (b) above dened for the STENT A. Six time instants are properly selected inside the cardiac cycle to report the temporal changes. Stent design Based on the suggestions in the literature indicating a threshold of 0.5 Pa as a critical WSS value to consider a region prone to restenosis, the corresponding artery wall and stent percentage area was evaluated to compare the performances of the four stents. Fig. 4 shows the histograms of the vessel area percentage with a WSS magnitudeo0.5 Pa for each stent model in the six selected time instants. A miniature of the time course of inlet velocity is also represented to help the reader to localize the time instants in the cardiac cycle. Low and high values alternate during the entire cardiac cycle. At blood-ow peaks i.e. at time instants 0.16 s

(diastolic perfusion) and 0.40 s (systolic heart ejection phase) the percentage area with WSSo0.5 Pa is around 30% for all stent models. It increases signicantly in the other time instants of the cycle, when blood ow is either decelerating or minimum. Such a behavior is common for all models with only slight differences for STENT D, that shows an increase in the area percentage in the last time instant (0.52 s) if compared to the slight decrease showed by the other three models. Comparing the four stent models, STENT B shows the highest percentage of area with low WSS values during the cardiac cycle, except for time points 0.16 s and 0.40 s, when area percentage is higher for STENT A. Fig. 5a shows the comparison in terms of maximum WSS values on the stent area and vessel area at the six selected time points in the cardiac cycle. The histograms illustrate the trend for STENT A only, being the same for the other ones. Comparing the vessel area and the stent area, the maximum values are located on the stent area. They remain above 1 Pa during the entire cardiac cycle and reach the maximum in the diastolic perfusion phase with a value of around 5 Pa. Fig. 5b reports the comparison in terms of maximum WSS values on the stent area. It can be noted that STENT A has the highest values along the cardiac cycle, whereas the other three models have

0.16 s

100 % of vessel area < 0.5 Pa 80 60 40 20 0 0s

0s

0.40 s 0.32 s 0.52 s 0.44 s

0.16 s
STENT A

0.32 s 0.40 s Time

STENT B STENT C

0.44 s

0.52 s

STENT D

Fig. 4. Histograms of the percentage of vascular wall surface with WSS values lower than 0.5 Pa for the four stent models reported at six time instants of the cardiac cycle, indicated in the miniature on the top.

Fig. 3. Fluid domain regions used to describe the results: the luminal side of the strut surface, named stent area (a) and the luminal side of the bare vascular wall surface, named vessel area (b).

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5 4 3 2 1 0 0s 0.16 s 0.32 s

VESSEL AREA STENT AREA

[Pa]

0.40 s

0.44 s

0.52 s
STENT A

5 4 3

STENT B STENT C STENT D

[Pa]

0.16s [m/s]

2 1 0 0s 2 1.5 [Pa] 1 0.5 0 0s 0.16 s 0.32 s 0.40 s Time 0.44 s 0.52 s 0.16 s 0.32 s 0.40 s 0.44 s
STENT A STENT B STENT C STENT D

0.40 s 0.32 s 0s 0.44 s [Time] 0.52 s

0.52 s

Fig. 5. Histograms of the maximum WSS values during a cardiac cycle: (a) comparison of the maximum values on the stent luminal side surface and the luminal side of the vascular wall surface within the stent struts for STENT A model; (b) comparison of WSS values on the stent area for the four stent models and (c) comparison of WSS values on the vessel area for the four stent models.

comparable results with decreasing values for STENT D, STENT C and STENT B, respectively. With regard to the vessel area among the stent struts, the histograms of the maximum WSS values show smaller differences among the four models with a little prevalence for STENT A (Fig. 5c). Fig. 6 illustrates the WSS spatial distribution on the stent area in the diastolic perfusion phase, at time point 0.16 s. It can be observed that the links are the sites where WSS values are the highest for each model except for STENT D, where the highest values are localized in the thinner strut regions. In STENT A, STENT B and STENT C models the curved parts of the links are the sites where the maximum stresses concentrate. Fig. 7 reports the WSS spatial distribution on the vessel area within the stent struts, at the same instant (t 0.16 s).

The pattern is quite similar for all models: the values increase from the zones near the stent struts towards the center of the vessel region. This distribution is in a good agreement with that found in the literature (LaDisa et al., 2003). Stent strut thickness The increase of the strut thickness was performed for STENT B model, only. An increment of the strut thickness was applied from its baseline measurement of 0.05 mm to a value of 0.15 mm. The choice of a higher thickness of 0.15 mm allowed the evaluation of two different aspects: the inuence of different thicknesses with the same stent design (STENT B, in this case) on the uid dynamic

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Fig. 6. Contour plots of the WSS magnitude values for the four stent models at 0.16 s. In the insets the sites where the highest values are identied.

reduces the extension of these region, but only during the deceleration instants, e.g. 0 s early diastole, 0.32 s end of diastole and 0.52 s end of ejection phase (systole). Differences in percentage area are minimum during the acceleration phases. Temporal averages of the percentage area over the whole cardiac cycle are reported in the miniature (right side of Fig. 8a) for the two models and conrm the slightly minor extension of low-WSS regions for a thicker strut. Fig. 8b reports the area percentage of WSS values lower than 0.5 Pa for STENT A and STENT B on the entire uid domain, indicating that STENT B has a higher percentage area with critical values for a longer period in the cardiac cycle with respect to STENT A. However temporal averages of the percentage area over the whole cardiac cycle (miniature histogram in Fig. 8b) show an almost equal extension of low-WSS regions. Discussion
Fig. 7. Contour plots of the WSS magnitude values on the arterial wall portion delimited by the links and the stent struts at the diastolic peak (0.16 s) for each stent model.

behavior and that of two dissimilar designs (STENT B vs. STENT A) with the same thickness of 0.15 mm. Fig. 8a shows the percentage vessel area subjected to low-WSS values for the two STENT B models on the entire uid domain. Comparing the two models, a thicker strut

The results here reported refer to the immediate postexpansion situation when the natural strut embedding has not occurred yet. Although this conguration does not correspond to the real one, use of such models allows the evaluation across different stent designs of important uid dynamic aspects which could promote or retard the biological phenomena involved. A correlation between the imposed input velocity waveform and the waveform of WSS on particular locations is

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100 %of vessel area < 0.5 Pa 80 60 40 20 0 0s 0.16 s

STENT B STENT B THICK

0.32 s

0.40 s

0.44 s

0.52 s

STENT A 100 80 60 40 20 0 0s 0.16 s 0.32 s Time

Fig. 8. Histograms of the vessel area percentage with WSS values lower than 0.5 Pa: (a) comparison of STENT B model with different thickness at different instants and averaged values over the whole cardiac cycle; (b) comparison of STENT B and STENT A models with the same thickness of 0.15 mm and averaged values over the whole cardiac cycle.

STENT B

%of vessel area < 0.5 Pa

60.6 57.3

0.40 s

0.44 s

0.52 s

found (results not shown). The time changes of maximum WSS magnitude at selected points or vessel areas follow the velocity waveform, i.e. the increasing WSS magnitude values correspond to the increasing velocity values and vice versa. Comparing the extent of the areas with WSS lower than 0.5 Pa for the four stent designs, STENT B seems to be the most inclined one to promote intimal thickening. These results are conrmed by the higher percentage of low-WSS values shown by STENT B when compared to STENT A with the same thickness of 0.15 mm. It is nonetheless evident that the differences among the selected stent models are not so marked as expected. A possible reason resides in the absence of a vessel curvature and in the use of a single-stent unit. We believe that removing these limitations would yield greater differences in the nal deployed conguration and hence in the vessel-stent interaction. As a consequence, the WSS distribution would be slightly dissimilar, too. Observing the WSS spatial distribution on the vascular wall surface, the highest values are found at the center of the vessel wall area delimited by the stent strut and links. This portion of the vessel wall is proportional to the area

delimited by the stent struts. STENT B, which has the widest space between the links in the circumferential direction, is indeed the one with the largest area exhibiting high shear stress values. The zones with low-WSS values are found near the stent struts at the diastolic peak and the largest ones are shown by the STENT A. Two additional zones of high WSS can be seen at the inlet and outlet sites of the conned arterial wall region for STENT A and, to a lesser degree, for STENT B and STENT C. This could be ascribed to the stent design and to the deformed conguration reached after the expansion that creates regions more or less exposed to the blood ow. STENT D model shows the most uniform spatial distribution due to its regular shape. With regard to the stent area, the highest WSS values are localized over the stent struts, which are the regions most exposed to the blood ow. In all the stents, the outer part of the stent area shows high WSS values which decrease towards the vessel wall. The comparison of two different thicknesses for the same stent design (STENT B) enlightens an unexpected behavior as a thicker strut reduces the overall percentage area with low WSS values in the deceleration phases. This occurrence

57.8

57.3

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disagrees with results in the literature, which reports an almost opposite effect (LaDisa et al., 2004). However, that study refers to steady-state simulations where the deformed stent geometry is not obtained from a conned expansion. In the present study this behavior is presumably due to the combination of a pulsatile ow with the deformed shape of the inner surface of the arterial wall. Use of an idealized straight, rigid geometry for the arterial vessel implies disregarding the natural curvature of the coronary tree, which induces alterations in the WSS distribution due to the radial forces and secondary ows. However, the implantation of a stent causes a straightening and a consequent stiffness of the vessel. Thus the assumption of rigid wall is acceptable in the stented portion, whereas it could result in a different WSS distribution and higher ow disturbances in the proximal and distal stent-to-artery transition regions. A uid structure interaction analysis could be useful to evaluate such a uid dynamic behavior. Use of the deformed artery conguration derived from the expansion of a thin strut could also be criticized because it has been obtained expanding stents with different thickness values. It is nonetheless believed that a slightly thicker strut does not change the compression of the plaque and the artery in a relevant way, as they are mainly deformed by the ination of the angioplasty balloon. All the above remarks underline the difculties in extracting geometrical recommendations for the stent design able to satisfy both uid dynamic and mechanical requirements. For instance, a thicker strut induces high WSS localized over the stent strut, but decreases the extent of areas with critical low WSS on the vessel area during blood deceleration phases. The region of the vessel between links and struts appears to be important: the greater its extension the higher the peak WSS values. It is therefore suggested to keep it as limited as possible in order to reduce the portion with peak values and making WSS distribution more spatially uniform. Conclusions Up to now an increasing number of stents have been designed, manufactured and marketed with different materials, exibility, thickness, length and design. In particular, regarding the last feature, stents differ in the type of interconnection between subsequent struts, the shape of the links and their number in the circumferential direction. As already suggested by a number of studies in the literature (Tominaga et al., 1992; Rogers and Edelman, 1995; Garasic et al., 2000; Peacock et al., 1995), the present study conrms that a link exists between the stent design parameters and the haemodynamic factors affecting the in-stent restenosis process. Additional work based on the use of anatomically realistic models is required to draw signicant inferences for stent design improvement.

Conict of interest On behalf of all Authors, I declare that they do not have any nancial and personal relationships with other people or organizations that could inappropriately inuence their work. Acknowledgment This work has been partially supported by the Italian Institute of Technology (IIT), within the project Models and methods for local drug delivery from nano/micro structured materials. References
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