Determination of the influence of stent strut thickness using the finite element method: implications for vascular injury and in-stent restenosis

Many clinical studies, including the ISAR-STEREO trial, have identified stent strut thickness as an independent predictor of in-stent restenosis where thinner struts result in lower restenosis than thicker struts. The aim of this study was to more conclusively identify the mechanical stimulus for in-stent restenosis using results from such clinical trials as the ISAR-STEREO trial. The mechanical environment in arteries stented with thin and thicker strut stents was investigated using numerical modelling techniques. Finite element models of the stents used in the ISAR-STEREO clinical trial were developed and the stents were deployed in idealised stenosed vessel geometries in order to compare the mechanical environment of the vessel for each stent. The stresses induced within the stented vessels by these stents were compared to determine the level of vascular injury caused to the artery by the stents with different strut thickness. The study found that when both stents were expanded to achieve the same initial maximum stent diameter that the thinner strut stent recoiled to a greater extent resulting in lower luminal gain but also lower stresses in the vessel wall, which is hypothesised to be responsible for the lower restenosis outcome. This study supports the hypothesis that arteries develop restenosis in response to injury, where high vessel stresses are a good measure of that injury. This study points to a critical stress level in arteries, above which an aggressive healing response leads to in-stent restenosis in stented vessels. Stents can be designed to reduce stresses in this range in arteries using preclinical tools such as numerical modelling.     

Nitinol versus stainless steel stents: acute thrombogenicity study in an ex vivo porcine model

Acute and subacute stents thrombosis along with thrombus mediating neointimal proliferation within the stent struts remain major concerns in coronary stenting. Up to date, there is an obvious lack of data on the thrombogenicity of stent materials in physiological conditions. This study was performed to compare the relative thrombogenicity of nitinol versus stainless steel stents. Nitinol stents were laser cut to reproduce the exact geometry of the stainless steel Palmaz stents and tested in an ex vivo AV shunt porcine model under controlled conditions. Nitinol stents presented only small amounts of white and/or red thrombus principally located at the strut intersections while Palmaz stents clearly exhibited more thrombus. As a result, 125I-fibrin(ogen) adsorption and (111)I-platelets adhesion were significantly lower on nitinol than on stainless steel devices (36%, p = 0.03 for fibrin(ogen) and 63%, p = 0.01 for platelet). These results were confirmed by scanning electron observations showing different thrombus morphologies for nitinol and stainless steel. Along with the unique mechanical properties of nitinol, its promising haemocompatibility demonstrated in our study may promote their increasing use for both peripheral and coronary revascularization procedures.     

Development of microporous covered stents: geometrical design of the luminal surface

To reduce in-stent restenosis rates we have developed newly designed covered stents, in which a stent strut is buried into a microporous elastomeric cover film to provide a physical barrier against tissue ingrowth and a pharmacological reservoir for drug-eluting. The covered stents were prepared by dip-coating balloon expandable stents mounted on a stainless steel rod in a segmented polyurethane (SPU) solution, and were subsequently subjected to laser-processed microporing (pore diameter, 100 microm; interpore distance, 200 microm). The covered stents, which possessed flat luminal surfaces and micropores that were homogeneously arranged on the whole surface of the covering film, were deployed into the bilateral common carotid arteries of normal New Zealand white rabbits. Angiography after one month of implantation showed all stents were patent with little thrombus formation. The mean thickness of the formed neointimal layers was 292 +/- 177 microm (n=8), which was close to the size in non-covered bare stent (231 +/- 58 microm, n=7), but markedly decreased (about 2/3) from that in the previously developed wrapping-type covered stents (415 +/- 173 microm, P<0.01, n=8).     

An automatic algorithm for detecting stent endothelialization from volumetric optical coherence tomography datasets

Recent research has suggested that endothelialization of vascular stents is crucial to reducing the risk of late stent thrombosis. With a resolution of approximately 10 microm, optical coherence tomography (OCT) may be an appropriate imaging modality for visualizing the vascular response to a stent and measuring the percentage of struts covered with an anti-thrombogenic cellular lining. We developed an image analysis program to locate covered and uncovered stent struts in OCT images of tissue-engineered blood vessels. The struts were found by exploiting the highly reflective and shadowing characteristics of the metallic stent material. Coverage was evaluated by comparing the luminal surface with the depth of the strut reflection. Strut coverage calculations were compared to manual assessment of OCT images and epi-fluorescence analysis of the stented grafts. Based on the manual assessment, the strut identification algorithm operated with a sensitivity of 93% and a specificity of 99%. The strut coverage algorithm was 81% sensitive and 96% specific. The present study indicates that the program can automatically determine percent cellular coverage from volumetric OCT datasets of blood vessel mimics. The program could potentially be extended to assessments of stent endothelialization in native stented arteries.     

Effects of overexpansion on stents' recoil, symmetry/asymmetry, and neointimal hyperplasia in aortas of hypercholesterolemic rabbits.

BACKGROUND: It is not known whether overexpansion modifies stent recoil, symmetric distribution of struts, and neointimal hyperplasia. OBJECTIVES: The objectives were (a) to evaluate whether stent overexpansion modifies the geometric configuration of the stent in the arterial wall, (b) to determine the relationship between overexpansion and stent recoil, and (c) to evaluate the relationship between the distribution of struts and neointimal hyperplasia. METHODS: Twenty tubular stainless steel 316L stents (3.0 and 3.5 mm in diameter) were implanted at 20 and 10 atm, respectively, in the abdominal aorta of New Zealand rabbits fed a hypercholesterolemic diet (1% cholesterol). Sham operations were also performed in seven animals. Eight weeks after implantation or sham operation, an intravascular ultrasound (IVUS) study was performed to measure stent recoil and aid in stent classification (symmetric or asymmetric) according to strut distribution. The degree of injury and neointimal hyperplasia were also evaluated in hematoxylin-eosin stained sections. RESULTS: The symmetry/asymmetry of stents assessed by IVUS, as well as the neointimal hyperplasia, was similar in both groups. Stent recoil was significantly greater in the 3.0-mm stent (overexpanded) group (0.28+/-0.02 mm), as compared with stent recoil in the 3.5-mm stent group (0.10+/-0.01 mm, P<.05). The neointimal hyperplasia in histological slices, independent of the implant technique, was predominantly in zones with higher strut concentration as compared with zones with fewer struts. CONCLUSIONS: Stent overexpansion enhanced stent recoil and did not modify symmetric and asymmetric strut distribution. Neointimal hyperplasia was not modified by the implant technique. Interestingly, significant hyperplasia was observed in locations with greater strut concentration, independent of overexpansion.     

载药复合支架的抗血管组织增生的研究

在氧化钛表面改性的国产不锈钢支架上涂覆一定量药物,制备出新型复合的抗增生载药支架.观察支架植入猪冠状动脉3个月后血管的开通情况及血管的内膜反应.将7枚国产的普通不锈钢支架和7枚制备的新型载药支架植入14头小型猪冠状动脉内,3个月后对支架植入段血管进行血管造影、光镜及电镜检查并进行免疫组织化学分析.冠状动脉造影显示动物处死前支架段血管开通率100%,支架X光下清晰可见,未经特殊抗血栓治疗,支架段血管内无血栓形成.扫描电镜显示两组支架表面都完全被血管内膜覆盖,表面光滑,无血栓形成.覆盖的血管内膜中内皮细胞沿血流方向成典型的铺路石状排列.组织学形态分析显示植入支架3个月后,所有支架植入段血管内膜都有明显的增生,增生内膜主要由细胞外基质和平滑肌细胞构成.结论:含有新型载药支架的冠状动脉血管段内膜增生厚度比普通不锈钢支架的冠状动脉血管段内膜增生厚度小,这种载药复合支架具有良好的应用前景,需扩大样本进行深入研究.     

Monte Carlo calculations of dose distributions around 32P and 198Au stents for intravascular brachytherapy.

3D dose distributions are calculated for a 32P impregnated stent and a 198Au stent for intravascular brachytherapy with the EGS4 Monte Carlo simulation code. The stents were modeled as a combination of eight helicoidal struts. This allowed investigation of the effect of the stent geometry and the electron absorption in the strut material on the dose distributions. Absorbed dose to water was calculated at radial distances ranging from 50 microm to 5 mm from the stent surface. The dose distributions around the stents are compared to the dose distribution around an intravascular brachy-therapy 192Ir source, also calculated with the EGS4 Monte Carlo code. The dose profiles near the struts show hot spots. At 50 microm distance a peak to valley ratio of 3 for 32P and 6 for 198Au in the dose distribution is obtained. For both the isotopes the inhomogeneities decrease with distance and at a radial depth of 350 microm the effect becomes negligible. The calculations showed the importance of the effect of the absorption in the stent material as this leads to a dose decrease to 67% for the 198Au stent and to 77% for 32P near the stent at a distance of 2 mm from the stent axis. It is concluded that from the dosimetric point of view, the 198Au stent is inferior to the 32P stent and the 192Ir source. Application of the 198Au stent in clinical practice requires further investigation of the importance of the adventitia in the restenosis process, and the tolerance dose of the intima.     

Platelet responses and coagulation activation on polylactide and heparin-polycaprolactone-L-lactide-coated polylactide stent struts

Despite modern stent technology and effective antiplatelet therapy, metallic stents carry the risk of (sub)acute thrombosis. Our aim was to examine short-term differences in platelet deposition and coagulation activation between biodegradable polylactide (PLA), heparin-polycaprolactone-L-lactide-coated polylactide (hepa-P(CL95/L-LA5)-PLA), and stainless steel (SS) stent struts. Gel-filtered platelets (GFP) and platelet-rich plasma (PRP) were labeled with 10 nM (3)H-serotonin. Platelet deposition was measured after incubation of the stent struts in human serum albumin-coated wells at 37 degrees C in either GFP or PRP. Platelet morphology was studied by scanning electron microscopy (SEM). For coagulation activation, the stent struts were incubated in either PRP or platelet-poor plasma (PPP), anticoagulated with D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK), followed by measurement of fibrinogen, thrombin time (TT), prothrombin fragment 1+2 (F1+2), and thrombin-antithrombin complex (TAT). SS showed adherence of larger amounts of GFPs than did PLA at a platelet density of 300 x 10(6)/mL (p < 0.05). Furthermore, representative SEM studies showed more platelet spreading on SS than on PLA stent struts. Between PLA and SS, coagulation activity did not differ at any assessment. Based on prolonged TT values in plasma, the heparin coating strongly inhibited coagulation (p < 0.05). The values of soluble TAT and F1+2 for PLA were similar to those of controls, i.e., to incubated suspensions without a stent strut. In conclusion, when compared with stainless steel, both PLA and hepa-P(CL95/L-LA5)-PLA appear hemocompatible as intravascular stent materials.     

Fretting crevice corrosion of stainless steel stem-CoCr femoral head connections: comparisons of materials, initial moisture, and offset length

Modular tapers continue to be used in a wide variety of orthopedic implants. In this study, stainless steel (ASTM F-1568) femoral hip stems combined with Co-Cr-Mo alloy heads (SS/CoCr) were tested in an in vitro fretting corrosion test set-up to assess the propensity for mechanically assisted corrosion. Three different aspects of the modular design were evaluated in this study: (1) material combination compared to CoCr/CoCr, (2) wet versus dry assembly for SS/CoCr couples, and (3) 0- and 6-mm head offset for SS/CoCr couples. Fretting corrosion tests over a range of cyclic loads up to 3300 N were performed, and continuous cyclic loading at 3300 N for 1 M cycles were performed on each group (n = 5). Fretting micromotion was measured as a function of cyclic load on select couples to detect the nature and extent of motion present. The results showed that SS/CoCr couples were more susceptible to fretting corrosion than CoCr/CoCr couples, that dry assembly does not prevent fretting corrosion from taking place but raises the onset load, and that 6-mm offset heads had higher visual evidence of fretting damage but showed mixed statistical results in terms of onset loads and OCP shifts and currents compared to the 0-mm offset samples. Current and voltage excursions over 1 million cycles tended to diminish towards their unloaded control levels but did not fully recover until cyclic loading ceased. Micromotion measurements indicated fretting motions in the range of 10-25 microm where 0-mm heads tended to piston on the trunion, while 6 mm heads tended to rock.     

Coronary Stent Strut Size Dependent Stress–Strain Response Investigated Using Micromechanical Finite Element Models

Cardiovascular stents are metal scaffolds that are used in the treatment of atherosclerosis. These devices are typically composed of very thin struts (< or = 100 microm thickness, for coronary applications). At this size-scale the question arises as to the suitability of using bulk material properties in stent design. This paper investigates the use of finite element analysis to predict the mechanical failure of stent struts, typical of the strut size used in coronary stents. 316 L stainless steel in uniaxial loading was considered. To accurately represent the constitutive behavior of the material at this size-scale, a computational micromechanics approach was taken involving an explicit representation of the grain structure in the steel struts, and the use of crystal plasticity theory to represent the constitutive behavior of the individual grains. The development of the finite element models is discussed and results are presented for the predictions of tensile mechanical behavior as a function of strut thickness. The results showed that using this modelling approach, a size effect, already seen experimentally, is produced. This has significant implications for stent design, especially in the context of the desire to produce smaller stents for small bore neurovascular and peripheral artery applications.     

A rapid and computationally inexpensive method to virtually implant current and next-generation stents into subject-specific computational fluid dynamics models

Computational modeling is often used to quantify hemodynamic alterations induced by stenting, but frequently uses simplified device or vascular representations. Based on a series of Boolean operations, we developed an efficient and robust method for assessing the influence of current and next-generation stents on local hemodynamics and vascular biomechanics quantified by computational fluid dynamics. Stent designs were parameterized to allow easy control over design features including the number, width and circumferential or longitudinal spacing of struts, as well as the implantation diameter and overall length. The approach allowed stents to be automatically regenerated for rapid analysis of the contribution of design features to resulting hemodynamic alterations. The applicability of the method was demonstrated with patient-specific models of a stented coronary artery bifurcation and basilar trunk aneurysm constructed from medical imaging data. In the coronary bifurcation, we analyzed the hemodynamic difference between closed-cell and open-cell stent geometries. We investigated the impact of decreased strut size in stents with a constant porosity for increasing flow stasis within the stented basilar aneurysm model. These examples demonstrate the current method can be used to investigate differences in stent performance in complex vascular beds for a variety of stenting procedures and clinical scenarios.     

Maps of optical differential pathlength factor of human adult forehead,somatosensory motor and occipital regions at multi-wavelengths in NIR

The optical differential pathlength factor (DPF) is an important parameter for physiological measurement using near infrared spectroscopy, but for the human adult head it has been available only for the forehead. Here we report measured DPF results for the forehead, somatosensory motor and occipital regions from measurements on 11 adult volunteers using a time-resolved optical imaging system. The optode separation was about 30 mm and the wavelengths used were 759 nm, 799 nm and 834 nm. Measured DPFs were 7.25 for the central forehead and 6.25 for the temple region at 799 nm. For the central somatosensory and occipital areas (10 mm above the inion), DPFs at 799 nm are 7.5 and 8.75, respectively. Less than 10% decreases of DPF for all these regions were observed when the wavelength increased from 759 nm to 834 nm. To compare these DPF maps with the anatomical structure of the head, a Monte Carlo simulation was carried out to calculate DPF for these regions by using a two-layered semi-infinite model and assuming the thickness of the upper layer to be the sum of the thicknesses of scalp and skull, which was measured from MRI images of a subject's head. The DPF data will be useful for quantitative monitoring of the haemodynamic changes occurring in adult heads.     

冠状动脉支架紧缩反弹行为有限元分析

冠状动脉支架作为经皮穿刺冠状动脉成形术中保持病变血管畅通的核心器件,其紧缩到球囊后保持力的大小直接关系到在输送过程中支架从球囊脱落的危险性.支架所选的材料主要为316L不锈钢,但钴铬合金以其独特的性能开始被关注.本文利用有限元方法系统地研究了专有支架设计,在不同支架材料下,紧缩到不同程度及支架筋尺寸的变化对支架紧缩反弹行为的影响.结果显示,在这些因素中,支架所选用的材料是影响支架反弹指标的最重要因素,钴铬合金材料支架的反弹量明显大于316L不锈钢支架,约为40%.因此,有限元方法对支架力学行为分析具有很大的帮助,为支架系统的优化设计提供了重要指导作用.     

Cell Area and Strut Distribution Changes of Bent Coronary Stents： A Finite Element Analysis

Coronary stents are metal coils or mesh tubes delivered to blocked vessels through catheters, whic Recently, special drugs h are expanded by balloons to reopen and scaffold target vessels. are carried by stents （drug-eluting stents） to further reduce instent restenosis rate after stenting procedure. However, continual study on biomechanical characteristics of stents is necessary provide a more suitable drug loading for better interactions between stents and tissue, or to platform for drug-eluting stents. The purpose of this paper is to show how finite element methods can be used to study cell area and strut distribution changes of bent coronary stents. A same bending deformation was applied to two commercial coronary stent models by a rigid curved vessel. Results show that the stent design influenced the changes of cell area and strut distribution under bending situation. The stent with links had more cell area changes at outer curvature, and the stent with peak-peak （ 〉 〈 ） strut design could have strut contact and overlapping at inner curvature. In conclusion, this finite element method can be used to study and compare cell area and strut distribution changes of bent stents, and to provide a convenient tool for designers in testing and improving biomechanical characteristics of new stents.     

Mesenchymal stem cell seeding promotes reendothelialization of the endovascular stent

This study is designed to make a novel cell seeding stent and to evaluate reendothelialization and anti-restenosis after the stent implantation. In comparison with cell seeding stents utilized in previous studies, Mesenchymal stem cells (MSCs) have advantages on promoting of issue repair. Thus it was employed to improve the reendothelialization effects of endovascular stent in present work. MSCs were isolated by density gradient centrifugation and determined as CD29(+) CD44(+) CD34(-) cells by immunofluorescence and immunocytochemistry; gluten and polylysine coated stents were prepared by ultrasonic atomization spray, and MSCs seeded stents were made through rotation culture according to the optimized conditions that were determined in previous studies. The results from animal experiments, in which male New Zealand white rabbits were used, show that the reendothelialization of MSCs coated stents can be completed within one month; in comparison with 316L stainless steel stents (316L SS stents) and gluten and polylysine coated stents, the intimal hyperplasia and in-stent restenosis are significantly inhibited by MSCs coated stents. Endovascular stent seeded with MSCs promotes reendothelialization and inhibits the intimal hyperplasia and in-stent restenosis compared with the 316L SS stents and the gluten and polylysine coated stents.     

The Stress–Strain Behavior of Coronary Stent Struts is Size Dependent

Coronary stents are used to re-establish the vascular lumen and flow conditions within the coronary arteries; the typical thickness of a stent strut is 100 m, and average grain sizes of approximately 25 m exist in stainless steel stents. The purpose of this study is to investigate the effect of strut size on the stress strain behavior of 316 L stainless steel. Other materials have shown a size dependence at the micron size scale; however, at present there are no studies that show a material property size dependence in coronary stents. Electropolished stainless steel stent struts within the size range of 60–500 m were tensile tested. The results showed that within the size range of coronary stent struts a size dependent stress–strain relationship is required to describe the material. Finite element models of the final phase of fracture, i.e., void growth models, explained partially the reason for this size effect. This study demonstrated that a size based stress–strain relationship must be used to describe the tensile behavior material of 316 L stainless steel at the size scale of coronary stent struts. © 2003 Biomedical Engineering Society. PAC2003: 8719Rr, 8780Rb, 8719Uv     

Three-dimensional numerical simulations of physiological flows in a stented coronary bifurcation

When atherosclerotic lesions are found within a coronary bifurcation, a double stent implantation is sometimes required to treat the disease of each branch. The clinical procedure can result in the positioning of several stents in the bifurcation. In the study, physiological flows in typical configurations of such stented coronary bifurcations were numerically modelled using the finite volumes method. Two deployed Palmaz stents were inserted in a 90° coronary bifurcation, simulating a double stent implantation. As the geometric position of the metallic stent cells can vary, several models of broken cells were proposed and compared to characterise the influence of the stent struts protruding into the collateral branch. Flow features in the bifurcation surroundings changed from one model to another. These changes could lead to the occurrence of flow stasis and also of recirculation areas downstream from the struts, depending on the way the strut was opened. The stent struts protruding into the lumen of the collateral branch induced high values of shear stress at the stent wall of about 20 Nm⁻², which could stimulate platelet activation. In addition, these areas of high shear stress values were concomitant with areas of low shear stress values of about 0.5 Nm⁻². These regions could be prone to platelet adhesion and so to thrombo-embolic complications. The analysis of the flow field indicated that it would be judicious to use dedicated bifurcated stents to treat bifurcation lesions.     

Self-absorption correction for 32P, 198Au and 188Re stents: dose point kernel calculations versus Monte Carlo

Monte Carlo simulations of dose distributions around radioactive stents are very time intensive. Thus, in order to calculate the dose distribution around a 188Re stent, we chose to test a point kernel method, a method which is known to be faster but the accuracy of which has not been established for this application. The dose point kernel method, which takes into account absorption in the strut material (=self-absorption), was based on different beta-emitting point source distributions in water by itself and surrounded by steel spheres of different thicknesses. This information was input into an integration routine that modeled either a Palmaz-Schatz or Multilink stent. The dose distributions around 198Au and 32P stents calculated with the dose point kernel method were compared to those calculated using EGS4 and MCNP 4B Monte Carlo methods. The resulting correction for self-absorption in steel was distance dependent and averaged 1.12 for 32P and 1.25 for 198Au stents. The dose point kernel method gave nearly identical results to these full Monte Carlo simulations and was thus used to calculate the dose distributions around a 188Re stent. Although 188Re has a half-life of only 17 hours, it is posited to be useful for radioactive restenosis prevention, given that a recently developed rapid electrodeposition procedure allows stents to be made radioactive, at predetermined activities, within 15 minutes. The dose point kernel calculations of a 188Re-coated Multilink stent were compared to its radiochromic film measurements. The dose fall-off agreed with the calculations within 5% over 0.4 to 3.5 mm from the stent surface. The dose point kernel method is a valuable tool to determine depth dose distributions around activated stents taking into account the detailed geometry and the self-absorption in the struts. It not only requires much less processing time than Monte Carlo methods, but also allows the use of higher resolutions in modeling the geometry, which leads to more accurate self-absorption correction factors.     

Polymer-free immobilization of a cyclic RGD peptide on a nitinol stent promotes integrin-dependent endothelial coverage of strut surfaces

This study examined the utility of a stabilized cyclic RGD peptide chemically modified to selectively bind to titanium-oxide for enhanced biocompatibility of self-expanding nitinol stents. Endothelial cells express integrin receptors that promote attachment to subendothelial matrix proteins. Integrin binding to arginine-glycine-aspartic acid (RGD) peptide derivatives mimic naturally occurring adherent interactions. Irreversible covalent surface coating of conventional nitinol stents with a cyclic RGD (cRGD) peptide highly specific for integrin alpha v beta 3 might foster endothelialization after stent implantation. A selective cRGD peptide was irreversibly immobilized onto titanium oxide-rich nitinol coupons or self-expanding stents. Functionality of the engrafted RGD peptide was demonstrated using in vitro endothelial bioassays. A subsequent 7-day in vivo endothelialization study was performed using cRGD-coated self-expanding nitinol stents in rabbits. cRGD peptide coating effectively promoted endothelial cell anchorage, migration, and proliferation confirmed by increased focal adhesions. Proof-of-concept studies of rabbit cRGD stent implants showed a significant increase in endothelial coverage above stent struts relative to stents coated with BSA (cRGD = 70.1 ± 21.9 vs. BSA = 49.9 ± 21.8%, p < 0.03). Immobilization of cRGD peptides on strut surfaces represents an innovative strategy to improve endothelialization, which may facilitate vascular healing after stent implantation.     

The degree of neointimal formation after stent placement in atherosclerotic rabbit iliac arteries is dependent on the underlying plaque.

The purpose of this study was to determine the effects of stent placement on the underlying arterial morphology and the relations of stent-vessel wall interactions with subsequent neointimal formation in an atherosclerotic artery. Seven New Zealand White rabbits with experimentally induced atherosclerosis underwent balloon angioplasty (n = 7) and stent placement after balloon angioplasty (n = 7) in the iliac arteries. Histologic analysis of the treated arteries was performed at 28 days to assess device interactions with the artery and the pattern of the neointimal response. The area within the external elastic lamina of the stented vessels was 66% greater than the arteries with balloon angioplasty alone (p = 0.001) which contributed to a significantly greater late lumen area (3.33 +/- 0.51 mm2 versus 1.33 +/- 0.20 mm2, p = 0.0028). Neointimal thickness was measured at 220 stent wire sites from 21 sections of stented arteries of which 139 (63%) had underlying plaque and 81 (37%) were adjacent to normal media. Rupture of the internal elastic lamina (IEL) occurred at only 9 (11%) of the 81 stent wire sites over normal media. The mean neointimal thickness was 0.16 +/- 0.01 mm lor all stent wire sites. The neointimal thickness was greater at the stent wire sites with underlying plaque (0.23 +/- 0.01 min) than at the stent wire sites adjacent to normal media (0.08 +/- 0.01 mm) or at sites with rupture of the internal elastic lamina (0.16 +/- 0.02 mm, p = 0.0001). The degree of neointimal formation within the stents strongly correlated with the area of the underlying atherosclerotic plaque (r = 0.76, p = 0.0007) and the extent of plaque or medial compression by the struts (r = 0.90, p = 0.006). The present study characterizes stent interactions in a model commonly employed to evaluate novel therapies for the prevention of restenosis. The neointimal response was influenced by the local arterial morphology and correlated with the extent of plaque or medial compression by the stent. These data may be useful for future studies in this model and understanding the mechanism of in-stent restenosis.