Porcine Coronary Restenosis Model Research Articles

Stent linker effect in a porcine coronary restenosis model

In this study, we aimed to evaluate the mechanical effects of different stent linker designs on in-stent restenosis in porcine coronary arteries. We fabricated stents with an open-cell structure composed of nine main cells and three linker structures in model 1 (I-type), model 2 (S-types) and model 3 (U-types)) as well as Model 4, which is similar to a commercial bare metal stent design. The stent cells were 70mm thick and wide, with a common symmetrical wave pattern. As the radial force increased, the number of main cells increased and the length of linker decreased. Radial force was higher in model 1, with a linear I-linker, than in models with S- or U-linkers. The flexibility measured by three-point bending showed a force of 1.09N in model 1, 0.35N in model 2, 0.19N in model 3, and 0.31N in model 4. The recoil results were similar in all models except model 4 and were related to the shape of the main cells. The foreshortening results were related to linker shape, with the lowest foreshortening observed in model 3 (U-linker). Restenosis areas in the porcine restenosis model 4 weeks after implantation were 35.4±8.39% (model 1), 30.4±7.56% (model 2), 40.6±9.87% (model 3) and 45.1±12.33% (model 4). In-stent restenosis rates measured by intravascular ultrasound (IVUS) and micro-computed tomography (micro-CT) showed similar trends as percent area stenosis measured by micro-CT. Model 2, with optimized flexibility and radial force due to its S-linker, showed significantly reduced restenosis in the animal model compared to stents with different linker designs. These results suggest that the optimal stent structure has a minimum radial force for vascular support and maximum flexibility for vascular conformability. The importance of the effects of these differences in stent design and their potential relationship with restenosis remains to be determined.

Dose-dependent vascular response following delivery of sirolimus via fast releasing, biodegradable polymer stent matrix: an experimental study in the porcine coronary model of restenosis.

Fast releasing, rapamycin-eluting stents, although safe, showed inferior results with regard to inhibition of restenosis. Therefore, we report vascular effects of a novel, biodegradable polymer stent matrix with elevated sirolimus dose and fast release kinetics (ed-frSES, Alex, Balton) in the porcine coronary in-stent restenosis model. A total of 19 stents were implanted with 120% overstretch in the coronary arteries of seven domestic pigs: seven ed-frSES with 1.3 μg/mm2 of sirolimus, eight frSES with 1 μg/mm2 of sirolimus, and eight bare metal stents (BMS). For the following 28 days, coronary angiography was performed, animals were sacrificed, and the stented segments harvested for histopathological evaluation. In angiography at 28 days the late lumen loss was lowest in the elevated dose sirolimus eluting stent (SES) (ed-frSES: 0.20 ± 0.2 vs. frSES: 0.80 ± 0.5 vs. BMS: 0.96 ± 0.5 mm, p < 0.01). This was confirmed in the morphometric evaluation in histopathology as represented by a significant and dose-dependent decrease in the percentage area of stenosis (ed-frSES: 22.4 ± 12.7% vs. frSES: 35 ± 10.7% vs. BMS: 47.5 ± 12.5%, p < 0.01). There was no peri-strut inflammation in any of the groups. However, the endothelialisation score was numerically not meaningfully decreased in ed-frSES (ed-frSES: 2.93 vs. frSES: 3. vs. BMS: 3, p = 0.05). Signs of fibrin were also noted in ed-frSES (ed-frSES: 0.4 vs. frSES: 0 vs. BMS: 0, p = 0.05). Sirolimus dose-dependent vascular response was reported. The elevated dose, fast releasing SES shows satisfactory vascular healing, similar to regular dose, fast release SES, with improved efficacy in restenosis inhibition.

Effect of pretreatment of ezetimibe/simvastatin on arterial healing and endothelialization after drug-eluting stent implantation in a porcine coronary restenosis model.

Background and ObjectivesWe sought to evaluate the effect of the early use of ezetimibe/simvastatin (Vytorin®) on arterial healing and endothelialization after the implantation of a drug-eluting stent (DES) in a porcine model of coronary restenosis.Materials and MethodsA total of 20 pigs (40 coronary arteries) were randomly allocated to a pretreatment or no treatment group. The pretreatment group (n=20) received oral ezetimibe/simvastatin (10/20 mg) daily for 7 days before stenting and the no pretreatment group (n=20) did not. All pigs were treated with ezetimibe/simvastatin (10/20 mg) daily after stenting for 4 weeks. Stenting was performed using a bare-metal stent (BMS, n=10) and three types of DES: biolimus A9-eluting stent (BES, n=10), zotarolimus-eluting stent (ZES, n=10), and everolimus-eluting stents (EES, n=10). Four weeks later, pigs underwent a follow-up coronary angiography and were sacrificed for histopathologic analysis.ResultsThere were no significant differences between the pretreatment and no pretreatment groups in the internal elastic lamina area, lumen area, neointima area, stenotic area, injury score, fibrin score, and inflammation score. In both groups, the fibrin score was higher in pigs with DES than in BMS, particularly in ZES and EES. The inflammatory score was not different between DES and BMS.ConclusionIn a porcine model of coronary restenosis, pretreatment with ezetimibe/simvastatin before DES implantation failed to improve arterial healing and endothelialization compared to treatment after stenting.

Biodegradable Polymer-Based Sirolimus Coating Stent in a Porcine Coronary Restenosis Model

Durable polymer-based first-generation sirolimus-eluting stents (SES) reduce the risks of in-stent restenosis (ISR) and revascularization compared to bare metal stents (BMS). Therefore, drug eluting stents (DES), such as those using sirolimus and paclitaxel, have increasingly become available and used for the treatment of atherosclerotic coronary artery stenosis lesions. However, the permanent polymer in these DES can cause chronic inflammation and hypersensitive reactions in the stented artery after drug release. This may lead to delayed re-endothelialization, delayed arterial healing, and late stent thrombosis. In order to overcome the shortcomings of durable polymers, new DES using biodegradable polymers have been developed. DES with biodegradable polymers have been shown to be safe and effective in clinical trials. For example, biolimus A9-eluting stents (BES, Biomatrix, Biosensors Interventional Technologies Pte Ltd., Singapore) were developed as a third-generation drug eluting stent containing a bioabsorbadable polymer (PLA, poly-L-lactic acid) with the highly lipophilic sirolimus derivative biolimus A9. The objective of the present study was to evaluate a biodegradable polymer-based sirolimus coating on a novel bare-metal stent in a porcine coronary restenosis model.

Comparison of sirolimus loaded PLGA-PEG Co-polymer coronary stent and bare metal stent in a porcine coronary restenosis model

The aim of this study was to compare the effect of the sirolimus loaded PLGA-PEG co-polymer coronary stent with that of the bare metal stent in a porcine coronary restenosis model. Pigs were randomized into two groups (10 pigs, 10 coronary arteries in each group), in which either the sirolimus loaded PLGA-PEG copolymer stent (SPPS, n=10) or the bare metal stent (BMS, n=10) was implanted in the coronary arteries. Histopathologic analysis was performed at 28 days after stenting. There were no significant differences in the injury score, internal elastic lamina (IEL) area, and inflammation score between the two groups. There were significant differences in the lumen area (3.6±0.42 mm2 in the SPPS group vs. 2.5±0.89 mm2 in the BMS group, p<0.001), in the neointimal area (1.2±0.34 mm2 in the SPPS group vs. 2.5±0.99 mm2 in the BMS group, p<0.001), in the percent area stenosis (26.0±6.58% in the SPPS group vs. 48.6±16.95% in the BMS group, p<0.001) and in the fibrin score (1.2±0.41 in the SPPS group vs. 0.5±0.26 in the BMS group, p<0.001). These results demonstrate that SPPS had a superior effect on suppression of neointimal hyperplasia than BMS at one month after stenting in a porcine coronary restenosis model.

Effect of polymer-free TiO2 stent coated with abciximab or alpha lipoic acid in porcine coronary restenosis model

BackgroundPolymer-free drug-eluting stents (DES) may overcome the shortcomings of polymer-based DES. The aim of this study was to examine the effect of the polymer-free TiO2 film-coated stent with abciximab or alpha lipoic acid in a porcine coronary overstretch restenosis model. MethodsPigs were randomized into four groups in which the coronary arteries (24 pigs, 48 coronaries in each group) had TiO2 film-coated stent with abciximab (TCA, n=12), TiO2 film-coated stent with alpha lipoic acid (TCALA, n=12), biolimus A9-eluting stents with biodegradable polymer (BES, n=12), and TiO2 film-coated stent (TCstent, n=12). Histopathologic analysis was performed at 28 days after stenting. ResultsThere was no significant difference in the injury score and internal elastic lamina (IEL) among the four groups. There were significant differences in the lumen area, neointima area, percent area stenosis, fibrin score, and inflammation score among the four groups [2.7±1.0mm2, 2.6±0.94mm2, 48.9±16.25%, 1.0 (range 0.0–3.0), 1.0 (range 0.0–2.0) in TCA stent group vs. 2.7±1.24mm2, 2.9±0.83mm2, 53.5±17.19%, 1.0 (range 0.0–2.0), 1.0 (range 0.0–2.0) in TCALA stent group vs. 2.7±1.30mm2, 2.6±1.06mm2, 50.1±23.20%, 2.0 (range 1.0–3.0), 2.0 (range 1.0–3.0) in BES group vs. 1.7±0.63mm2, 3.3±0.58mm2, 60.2±10.12%, 0.5 (range 0.0–2.0), 1.0 (range 0.0–2.0) in TC stent group, respectively]. ConclusionTCA and TCALA are more effective to reduce neointimal hyperplasia compared to TC. Moreover, fibrin and inflammation scores are significantly lower in TCA and TCALA than BES in porcine coronary restenosis model.

Abciximab-Krueppel-like factor 4-plasmid-titanium dioxide coated coronary stent for inhibition of neointimal hyperplasia

Purpose: We developed dual system in delivery of gene and drug for coronary stent. For local gene delivery, denatured polymer coating was used. For drug delivery, titanium dioxide (TiO2) thin film which was non-polymer and had a high blood compatibility was used. In this study, we hypothesized whether dual delivery system of gene and drug for coronary stent was useful in preventing in-stent restenosis (ISR). Methods and results: The coating and modification of TiO2 thin film were manipulated by plasma enhanced chemical vapor deposition (PECVD) method. In vitro study, TiO2-Drug (Abciximab) coating stainless steel (SS) plate catch a larger amount of gWIZ-beta gal (beta-gal) plasmid compared with TiO2-only coating SS plate (2.70±0.32 vs. 7.17±0.38 mg/cm2, p<0.05). Also, the binding plasmid (Krueppel-Like Factor 4, KLF4) was effectively transfected into 293 cells after detachment using plasmid elution buffer. The reverse transfection using direct attachment of pig coronary artery smooth muscles showed the X-gal stain positive cells after 5 days. For analysis of in vivo gene delivery, we used animal models of rat abdominal skin and pig coronary artery. At 5 days after implantation of TiO2-Drug-beta-gal plasmid SS plate in rat abdominal skin, the expression of the beta-gal plasmid was observed. At 5 days after implantation of TiO2-Drug-beta-gal plasmid binding coronary stent in balloon-injured porcine coronary artery restenosis model, X-gal stained linear area was observed. To analyze the inhibitory effect of ISR, we used both TiO2-Abciximab-KLF4-plasmid-cobalt chromium (TAK-CC) and TiO2-only coating CC (T-CC) stent. Four weeks after implantation in porcine coronary artery, in histomorphometric analysis, TAK-CC stent group decreased ISR compared with T-CC group (TAK-CC group: 26.38±10.79% vs. T-CC group: 48.59±20.17%, n=6 in each, p<0.05). Also, both TAK-CC and T-CC stent group did not show the fibrin deposition at Castars' stain and accelerated re-endothelialization indicated by detectable anti-CD31 positive stained cells compared with commercial available paclitaxel-eluting stent. Conclusions: Our study implicate that this novel new system could be useful for coronary stent and other biomedical devices through dual delivery of gene and drug.

Cutting balloon combined with paclitaxel-eluting balloon for treatment of in-stent restenosis

The optimal therapy for in-stent restenosis (ISR) is controversial. We evaluated three different strategies for the treatment of in-stent restenosis: cutting balloon angioplasty (CBA), paclitaxel-eluting balloon angioplasty (PEBA) and cutting balloon followed by paclitaxel-eluting balloon angioplasty (CB+PEBA). Forty-five coronary arteries in 45 mini-pigs underwent oversized bare-metal stent (stent-to-artery ratio, 1.2:1) implantation to induce in-stent restenosis. After 28 days, vessels with in-stent restenosis (≥50% diameter stenosis) were randomly divided into three groups: CBA, PEBA and CB+PEBA. In vivo angiography was performed before intervention, immediately after intervention and at 28-day follow-up. Stented arteries were harvested for pathological analyses. The proliferation and apoptosis of vascular smooth muscle cells were evaluated by immunohistochemical staining and the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, respectively. Acute lumen gain was not different between the three groups. Late lumen loss and neointimal area at follow-up were lower for CB+PEBA compared with CBA but similar for CB+PEBA compared with PEBA. There were no significant differences in proliferating cell nuclear antigen-positive vascular smooth muscle cells and TUNEL-positive vascular smooth muscle cells between the CB+PEBA and PEBA groups. PEBA with or without cutting balloon was superior to CBA alone for in-stent restenosis. The underlying mechanism was probably related to inhibition of smooth muscle cell proliferation and increased apoptosis. In this porcine coronary artery restenosis model, PEBA with or without cutting balloon was superior.

Mechanical and Histopathological Comparison between Commercialized and Newly Designed Coronary Bare Metal Stents in a Porcine Coronary Restenosis Model

The aim of this study was to compare the stent designed by Chonnam National University Hospital (designated as CNUH) with commercial cobalt-chromium coronary stent in a porcine coronary overstretch restenosis model. CNUH stent was subjected to mechanical performance tests. Pigs were randomized into two groups in which the coronary arteries (10 pigs, 10 coronaries in each group) had either CNUH stent or control commercial bare metal stent. Histopathologic analysis was assessed at 28 days after stenting. In mechanical performance tests, CNUH stent showed 2.65N, 35.1N, 0.52N, 1.94%, 4.29% in the flat plate radial compression, radial force, 3 point bending, Foreshortening and recoil test, respectively. There was no significant difference in the injury score, internal elastic lamina (IEL), lumen area, neointima area, percent area stenosis, inflammation score and fibrin score between the two groups (1.2±0.35, 4.1±0.41 mm2, 2.7±0.56 mm2, 1.6±0.47 mm2, 36.7±11.2%, 1.2±0.62, 0.2±0.34 in CNUH stent group vs. 1.2±0.38, 3.7±0.64 mm2, 2.5±0.49 mm2, 1.5±0.61 mm2, 36.3±12.17%, 1.1±0.12, 0.4±0.46 in commercial stent group, respectively). In the mechanical performance test, CNUH stent showed the moderated performance under the guideline of FDA. CNUH stent demonstrated similar histological reactions compared with commercial cobalt-chromium stent in a porcine coronary overstretch restenosis model.

Histopathological Comparison among Biolimus, Zotarolimus and Everolimus-Eluting Stents in Porcine Coronary Restenosis Model

Background and ObjectivesThe aim of this study was to examine the histolopathogical effects among the biolimus, zotarolimus, and everolimus eluting stent (EES) in the porcine coronary restenosis model.Subjects and MethodsPigs were randomized into three groups in which the coronary arteries (15 pigs, 10 coronaries in each group) had either a biolimus A9 eluting stent (BES, n=10), zotarolimus eluting stent (ZES, n=10) or an EES (n=10). Histopathologic analysis was performed at 28 days after stenting.ResultsThere were no significant differences in the injury score among the three groups. There was a significant difference in the internal elastic lamina, lumen area, neointima area, percent area stenosis, and the fibrin and inflammation score among the three groups (4.3±0.53 mm2, 2.5±0.93 mm2, 1.8±1.03 mm2, 40.7±20.80%, 1.7±0.41, 1.4±0.72 in the BES group vs. 5.1±0.55 mm2, 2.3±1.14 mm2, 2.8±1.00 mm2, 55.4±21.23%, 2.0±0.39, 1.6±0.76 in the ZES group vs. 4.4±0.53 mm2, 1.7±1.22 mm2, 2.8±1.23 mm2, 64.0±26.00%, 1.8±0.76, 2.1±0.90 in the EES group, respectively). BES is more effective in inhibiting neointimal hyperplasia compared to ZES and EES (p<0.0001). According to the fibrin and inflammation score, BES and EES are more effective in decreasing the fibrin deposition compared to ZES (p<0.001). Moreover, BES and ZES are more effective in reducing the inflammatory reaction compared to EES (p<0.001).ConclusionThe result demonstrates that BES shows better histopathological characteristics than ZES and EES at one month after stenting in the porcine coronary restenosis model.

876 Anti-proliferative and anti-inflammatory effects of Ramiprilat-coated stent in a porcine coronary overstretch restenosis model

Background: The angiotensin-converting enzyme inhibitor ramiprilat has been previously demonstrated to protect myocardium from ischemia/reperfusion injury. Objectives: The aim of this study was to examine the anti-proliferative and anti-inflammatory effects of ramiprilat-coated stent in a porcine coronary overstretch restenosis model. Methods: Pigs were randomized into two groups in which the coronary arteries (16 pigs, 16 coronaries in each group) had either a ramiprilat-coated MAC stent or control MAC stent (AMG, Munich, Germany). Stents were deployed with oversizing (stent/artery ratio 1.3:1) in porcine coronary arteries, and histopathologic analysis was assessed at 28 days after stenting. Results: There were no significant differences in the neointima area normalized to injury score and inflammation score between the two groups (1.58 ± 0.43, 1.60 ± 0.39 in ramiprilat stent group vs. 1.60 ± 0.57, 1.62 ± 0.49 in control stent group, respectively). In neointima, most inflammatory cells were lymphohistiocytes. Overall, significant positive correlations were found between the lymphohistiocyte count and the neointima area (r = 0.567, p < 0.001) and between the lymphohistiocyte count and the percent area stenosis (r = 0.478, p < 0.001). Although lymphohistiocyte count (170 ± 121 cells vs. 162 ± 83 cells) and fibrin scores (0.15 ± 0.06 vs. 0.17 ± 0.07, p = 0.8) were not different between both groups, there was a strong trend of smaller neointima area (1.06 ± 0.51 mm2 vs. 1.28 ± 0.35 mm2, p = 0.083) and percent area stenosis (18.9 ± 8.7% vs. 22.8 ± 7.2%, p = 0.088) in the ramiprilat stent group compared with control group. Conclusions: Ramiprilat-coated stent showed a trend of more inhibitory effects on neointimal hyperplasia without differences in effects on inflammatory cell infiltration and arterial healing compared with control stent in a porcine coronary restenosis model.

AS-205 The Effects of Ramiprilat-Coated Stent on Neointimal Hyperplasia, Inflammation, and Arterial Healing in Porcine Coronary Restenosis Model

AS-205 The Effects of Ramiprilat-Coated Stent on Neointimal Hyperplasia, Inflammation, and Arterial Healing in Porcine Coronary Restenosis Model

Comparative assessment of drug-eluting balloons in an advanced porcine model of coronary restenosis

The advent of drug-eluting balloon (DEB) therapy has represented an important development in interventional cardiology. Nevertheless, preclinical data with this technology remain scant, and comparative studies have not previously been published. Bare metal stents were implanted in the coronary arteries of 15 pigs followed by balloon angioplasty. Animals were allocated to treatment with a 60-second inflation of one of four different balloon catheters: a conventional untreated plain angioplasty balloon (PBA, Biotronik AG), the Pantera Lux DEB (3.0 μg/mm2 paclitaxel; BTHC excipient, Biotronik AG), the Elutax DEB (2.0 μg/mm2 paclitaxel; no excipient; Aachen Resonance), or the SeQuent Please DEB (3.0 μg/mm2 paclitaxel; iopromide excipient: B. Braun). Twenty-eight days following balloon deployment, animals underwent repeat angiography for quantitative coronary angiography analysis and euthanasia for histopathologic assessment. By histology, the mean neointimal thickness was 0.44 ± 0.19 mm with PBA, 0.35 ± 0.13 mm with Pantera Lux , 0.61 ± 0.20 mm with Elutax , and 0.47 ± 0.21 mm with SeQuent Please DEB (p=0.02). In comparison with PBA, deployment of the Pantera Lux or the SeQuent Please DEB resulted in delayed healing characterised by significant increases in fibrin, neointimal cell vacuity and delayed re-endothelialisation. In conclusion, investigation of comparative DEB performance in a porcine model of advanced coronary restenosis reveals significant heterogeneity of neointimal suppression between the devices tested with numerically lowest values seen in the Pantera Lux group. On the other hand, evidence of delayed healing was observed in the most effective DEB groups.

Effects of Ramiprilat-Coated Stents on Neointimal Hyperplasia, Inflammation, and Arterial Healing in a Porcine Coronary Restenosis Model

Background and ObjectivesThe renin-angiotensin-aldosterone system has been implicated in the pathogenesis of neointimal hyperplasia, and a role for angiotensin II in the migration and proliferation of vascular smooth muscle cells in restenotic lesions has been proposed. The aim of this study was to determine the anti-proliferative and anti-inflammatory effects of ramiprilat-coated stents in a porcine coronary overstretch restenosis model.Subjects and MethodsPigs were randomized into two groups in which the coronary arteries {16 pigs (16 coronaries in each group)} had a 3.0×17 mm ramiprilat-coated MAC stent or a 3.0×17 mm control MAC stent (AMG, Munich, Germany) implanted with oversizing (stent-to-artery ratio, 1.3 : 1) in porcine coronary arteries, and histopathologic analysis was assessed 28 days after stenting.ResultsThere were no significant differences in the injury and inflammation scores between the two groups (1.20±0.43 vs. 1.23±0.57, p=0.8; and 1.21±0.39 vs. 1.25±0.49, p=0.6, respectively). Within the neointima, most inflammatory cells were lymphohistiocytes. Significant positive correlations existed between inflammatory cell counts and the neointima areas (r=0.567, p<0.001), and between inflammatory cell counts and the percent area stenosis (r=0.478, p<0.001). There was no significant difference in the inflammatory cell counts normalized to the injury (110±89 vs. 123±83, p=0.4) and fibrin scores (0.15±0.06 vs. 0.17±0.07, p=0.8) between the 2 groups. There were trends toward a smaller neointima area (1.06±0.51 mm2 vs. 1.28±0.35 mm2, p=0.083) and a smaller percent area stenosis (18.9±8.7% vs. 21.8±7.2%, p=0.088) in the ramiprilat-coated stent group.ConclusionAlthough the ramiprilat-coated stent did not show significant inhibitory effects on neointimal hyperplasia, the ramiprilat-coated stent showed good effects on the inflammatory reaction and arterial healing similar to the control stent in a porcine coronary restenosis model.

Effect of a Dual Drug-Coated Stent With Abciximab and Alpha-Lipoic Acid in a Porcine Coronary Restenosis Model

Background and ObjectivesThe aim of this study was to examine the anti-proliferative and anti-inflammatory effects of a stent coated with abciximab and alpha-lipoic acid (ALA) in a porcine coronary overstretch restenosis model.Materials and MethodsA total of 10 pigs were randomized into two groups (10 pigs, 10 coronaries in each group) in which the coronary arteries were stented with a dual-coated stent and a bare metal stent (control) by randomization. Stents were deployed with oversizing (stent/artery ratio 1.3 : 1) in the porcine coronary arteries, and histopathology was assessed 28 days after stenting.ResultsThere was no significant difference in the injury score between the two groups. In the neointima, the lymphohistiocyte count was significantly lower in dual-coat stent group compared with the control stent group (120±85 cells vs. 159±80 cells, p=0.048). There was no significant difference in the fibrin score between the two groups (0.16±0.34 in the dual-coated stent group vs. 0.25±0.48 in the control stent group, p=0.446). The neointima area was not significantly different between both groups (1.55±0.8 mm2 in dual-coated stent group vs. 1.40±0.86 mm2 in the control stent group, p=0.447).ConclusionAlthough the dual-coated stent with abciximab and ALA showed no significant difference in inhibition of neointimal hyperplasia when compared with the bare metal stent, it was associated with a reduced inflammatory reaction when compared with the control stent in a porcine coronary restenosis model.

Drug-Coated Balloons for the Prevention of Vascular Restenosis

From early in the history of percutaneous cardiovascular intervention, restenosis has been one of the most important clinical and biological measures of success, and a great deal of effort has been put into understanding the mechanisms responsible.1,2 Restenosis is the result of the interaction of a variety of mechanical and biological processes that begin immediately after balloon injury, including early vessel recoil,3,4 negative vascular remodeling,5 and excessive neointimal proliferation.5–7 The most important limitations of balloon angioplasty, abrupt vessel closure resulting from elastic recoil and occlusive plaque dissection, were effectively solved by the introduction of balloon-expandable stents.8 However, in-stent restenosis (ISR), the result of the initial injury and the vascular response to the implanted metallic prosthesis leading to excessive neointimal proliferation, remained as the most important cause of failure of these devices.9,10 Drug-eluting stents (DES) effectively reduced ISR by addressing the biological mechanisms of neointimal proliferation and have become the mainstay of the interventional treatment of coronary atherosclerotic disease.11 However, the demonstrated efficacy of DES is balanced by the small but unpredictable risk of very late stent thrombosis thought to be due to delayed vascular healing resulting from either the initial antiproliferative effect (and associated late acquired incomplete stent apposition) or a hypersensitivity reaction to the drug, polymer coating, or their combination.12,13 Moreover, beyond the coronary vasculature, there has been a paucity of effective therapies to manage restenosis after intervention. In recent years, drug-coated balloons (DCBs) have emerged as a therapeutic alternative in the interventional field.14 With this technology, short-term transfer of antiproliferative drugs to the arterial wall is achieved without the requirement of an implanted drug delivery system, thus potentially reducing the untoward effects associated with polymer-based stent technologies. In small clinical randomized trials, paclitaxel-coated balloons have been shown to be …

Effects of Combined Therapy with Ezetimibe Plus Simvastatin After Drug-Eluting Stent Implantation in a Porcine Coronary Restenosis Model

The aim of this study was to examine the anti-proliferative and anti-inflammatory effects of ezetimibe/simvastatin (E/S) after drug-eluting stent (DES) implantation in a porcine coronary restenosis model. Pigs were randomized into two groups in which the coronary arteries (23 pigs) had DES. Stents were deployed with oversizing (stent/artery ratio 1.3:1) in porcine coronary arteries. Fifteen pigs were taken 10/20 mg of E/S and eight pigs were not taken E/S. Histopathologic analysis was assessed at 28 days after stenting. In neointima, most inflammatory cells were lymphohistiocytes. Lymphohistiocyte count was not different between two groups (337±227 vs. 443±366 cells, P=0.292), but neointima area was significantly smaller (1.00±0.49 mm2 vs. 1.69±0.98 mm2, P=0.021) and percent area stenosis was significantly lower (23.3±10% vs. 39±19%, P=0.007) in E/S group compared with control group. There were no significant differences in fibrin score (1.99±0.79 vs. 1.81±0.88, P=0.49), endothelial score (1.75±0.66 vs. 1.80±0.59, P=0.79), and the percent of endothelium covered lumen (43±21% vs. 45±21%, P=0.84) between E/S group and control group. Combined therapy with ezetimibe and simvastatin inhibits neointimal hyperplasia, but does not inhibit inflammatory infiltration and arterial healing after DES implantation in a porcine coronary restenosis model.

TCT-490: Anti-Inflammatory Effect of Abciximab-Coated Stent in a Porcine Coronary Restenosis Model

TCT-490: Anti-Inflammatory Effect of Abciximab-Coated Stent in a Porcine Coronary Restenosis Model

TCT-489: Effect of Dual Coating Stent with Abciximab and Alpha-Lipoic Acid in a Porcine Coronary Restenosis Model

TCT-489: Effect of Dual Coating Stent with Abciximab and Alpha-Lipoic Acid in a Porcine Coronary Restenosis Model

Drug-Eluting Stents in Animals and Patients

Four legs good, two legs better. — —George Orwell, Animal Farm, 1945 Since the earliest use of coronary stents for treating symptomatic coronary stenosis, maintaining patent arteries after treatment has remained an elusive goal. Although the first bare metal stents opened stenotic arteries, they injured the arterial wall. The buildup of intimal scar tissue caused restenosis, a frustrating problem for prevention or treatment. After a dozen years of research, however, drug-eluting stents were developed; armed with polymer coating and paclitaxel or sirolimus, they prevented restenosis and were hailed as a major therapeutic breakthrough. Article see p 141 Not long afterward, however, questions about the safety and efficacy of drug-eluting stents surfaced as reports of late stent thrombosis began to appear.1,2 Cardiologists wondered if prevention of restenosis was always a good thing. If no protective cellular layer formed over the struts of the drug-eluting stent—even months or years after implantation—would thrombus develop on the exposed metal scaffolding or other damaged or inflamed areas on the blood vessel wall? Over months or years, would progressive inflammation or late “catchup” tissue growth cause drug-eluting stents to lose their early advantage over bare metal stents? The pendulum in this debate has swung back and forth as clinical trials first raised concern about increased thrombosis and then later quelled our fears as our understanding of how drug-eluting stents work in real life has matured. An important issue has been the increased use of stents in patients with more complex coronary and other disorders, raising the question of whether the established standards of safety and efficacy still apply. Answers for these challenging questions have come from 2 worlds: clinical studies of patients with stents …