Mytrolimus药物洗脱支架预防支架内再狭窄的实验研究

目的评价新型聚烯烃类高分子化合物涂层携载雷帕霉素衍生物-Mytrolimus(CCI-779)洗脱支架在小型猪冠状动脉模型预防再狭窄的疗效。方法小型猪冠状动脉分别置入裸支架、单纯聚烯烃类高分子化合物涂层支架和Mytrolimus洗脱支架(160μg/18mm)。术后4周重复冠状动脉造影后处死动物,测定3组支架血管段的损伤指数、冠状动脉横截面积、管腔面积、支架上平均内膜厚度、支架间平均内膜厚度、新生内膜面积、面积再狭窄百分比,并作比较。结果裸支架组(置入支架数n=10)、单纯聚烯烃类高分子化合物涂层支架组(n=10)和Mytrolimus洗脱支架组(n=8)3组冠状动脉大小和血管损伤程度基本相同,术后4周,单纯聚烯烃类高分子化合物涂层组与裸支架比较多项参数差异均无统计学意义。Mytrolimus药物洗脱支架组和裸支架组的支架上内膜厚度分别为(0.18±0.08)mm和(0.33±0.25)mm(P<0.05);支架间内膜厚度分别为(0.14±0.05)mm和(0.28±0.23)mm(P<0.05);新生内膜面积分别为(1.09±0.24)mm2和(2.44±1.59)mm2(P<0.05)。上述多项参数在Mytroliums洗脱支架组均显著少于裸支架组。Mytrolimus组新生内膜面积比裸支架组少了55.33%,且Mytrolimus组无一例再狭窄。结论Mytrolimus洗脱支架在置入小型猪冠状动脉4周时可有效抑制内膜增生、预防冠状动脉实验性支架内再狭窄。     

Atorvastatin stent coating does not reduce neointimal proliferation after coronary stenting

PURPOSE: Statins seem to be suitable for restenosis prevention via reduction of smooth muscle cell proliferation, anti-inflammatory effects, and improvement of endothelial function. The aim of the present study was to test the efficacy of an atorvastatin stent coating for restenosis inhibition in the porcine coronary stent model. METHODS AND RESULTS: Twenty stents (BiodivYsio Matrix LO, uncoated or with 56 microg atorvastatin load) were implanted in LAD and CX coronary arteries of 10 domestic pigs with an over stretch ratio of 1.25. Quantitative angiography and histomorphometry of the stented arteries asserted statistic equality of the baseline parameters between the control and treatment group. After 28 days, there was no significant difference in parameters describing in-stent restenosis (neointimal area 3.14 +/- 1.13 mm(2) [control] vs. 3.12 +/- 1.07 mm(2) [atorvastatin stent]; p = 0.978). However, there was a trend towards a lower degree of inflammation in the atorvastatin stent group. CONCLUSION: Atorvastatin stent coating showed a trend towards reduced local inflammation near the stent struts, but could not reduce neointimal formation in the porcine coronary over stretch model.     

Advanced c-myc antisense (AVI-4126)-eluting phosphorylcholine-coated stent implantation is associated with complete vascular healing and reduced neointimal formation in the porcine coronary restenosis model.

An advanced six-ring morpholino backbone c-myc antisense (AVI-4126) was shown to inhibit c-myc expression and intimal hyperplasia after local catheter delivery in a porcine balloon injury model. The purpose of this study was to investigate the effects of an AVI-4126-eluting phosphorylcholine-coated (PC) stent on c-myc expression restenosis and vascular healing after stent implantation in porcine coronary arteries. PC stents were loaded with AVI-4126 using soak trap. Nine pigs underwent AVI-4126 PC coronary stent implantation (two stents/animal). Two to six hours postprocedure, three pigs were sacrificed and stented segments were analyzed by Western blot for c-myc expression. In chronic experiments, six pigs (12 stent sites) were sacrificed at 28 days following intervention and vessels were perfusion-fixed. High-performance liquid chromatography analysis of plasma samples showed minimal presence of the antisense. Western blot analysis of the stented vessels demonstrated inhibition of c-myc expression at 2 and 6 hr after procedure. Quantitative histologic morphometry showed that the neointimal area was significantly reduced (by 40%) in the antisense-coated group compared with control (2.3 +/- 0.7 vs. 3.9 +/- 0.8 mm(2), respectively; P = 0.0077). Immunostaining and electron microscopy demonstrated complete endothelialization, without fibrin deposition, thrombosis, or necrosis in all implanted stents. In the porcine coronary model, an advanced c-myc-eluting PC stent blocked c-myc expression and significantly inhibited myointimal hyperplasia and allowed complete reendothelialization and healing response.     

Stent Deployment Pressure Defines the Stent/Vessel Wall Relationship and has Important Implications for Early and Late Outcome

OBJECTIVE: This study evaluates the effect of stent deployment pressure on stent deployment, coronary vessel injury, subacute reclosure and foreign body reaction in a porcine coronary model. METHODS: Stainless steel coil stents were deployed in the right coronary artery of 30 pigs either using a deployment pressure of 4 atm (group I), 8 atm (group II), or 14 atm (group III). Serial quantitative angiographic studies together with morphometric analysis of the stented vessels were performed. RESULTS: Three pigs died within 48 hours due to subacute thrombosis (group I: n = 1, group II: n = 0, group III: n = 2). Another 4 stents were found occluded at day 7 (group I: n = 3, group II: n = 0, group III: n = 1). Imperfect stent alignment was found in 8 coronary arteries (group I: n = 7, group II: n = 1, group III: n = 0). Deep protrusion of stent filaments was found in 7 coronary arteries (group I: n = 0, group II: n = 1, group III: n = 6). Area stenosis at 6 weeks of the patent vessels was as follows: 75.7 +/- 15.2% in group I, 31.8 +/- 12.3% in group II, and 66.9 +/- 21.4% in group III, p < 0.001). CONCLUSION: In a porcine coronary model, stent deployment pressure resulting in an optimal alignment and a minimal coronary vessel injury leads to minimal neointimal hyperplasia.     

Novel site-specific systemic delivery of Rapamycin with perfluorobutane gas microbubble carrier reduced neointimal formation in a porcine coronary restenosis model.

Earlier studies demonstrated that perfluorobutane gas microbubble carrier (PGMC) adheres to injured arteries and enhances the drug uptake specifically into the cells of the denuded vessel segment. The purpose of this study was to investigate the effect of PGMC-based systemic delivery of Rapamycin on expression of p27 in vascular tissue and restenosis in porcine coronary arteries after stent implantation. Eight pigs underwent coronary stent implantation (three stents per animal). Five pigs were treated with i.v. injection of PGMC with 2 mg of Rapamycin and three animals served as control. Four hours postprocedure, three pigs were sacrificed and stented segments were analyzed by high-performance liquid chromatography (HPLC) and Western blot. In chronic experiments, five pigs (15 stent sites) were sacrificed at 28 days following intervention and vessels were perfusion-fixed. HPLC of the treated arteries demonstrated high drug concentration in the vessel tissue, and Western blot analysis showed elevated expression of p27 at 4 hr postprocedure. Histomorphometry revealed significantly reduced (by 40%) neointimal formation in the PGMC/Rapamycin group compared with controls (1.84 +/- 0.84 vs. 4.77 +/- 1.71 mm2, respectively; P < 0.001). In the porcine coronary model, site-specific systemic delivery of Rapamycin utilizing PGMC resulted in overexpression of p27 and a significant reduction of neointimal formation within the stented segments.     

Paclitaxel-coated Gianturco-Roubin II (GR II) stents reduce neointimal hyperplasia in a porcine coronary in-stent restenosis model.

BACKGROUND: Drug-coated stents may treat both mechanisms of restenosis, namely, geometric remodeling and neointimal hyperplasia. Paclitaxel, an antimicrotubule agent, has been shown to inhibit smooth muscle cell proliferation and migration, and may be an excellent candidate for local elution from a stent platform. METHODS: To study the antirestenosis effects of drug-coated stents, we impregnated paclitaxel (175-200 microg/stent with programmed elution over 6 months) on Gianturco-Roubin II (GR II) stents. These stents and control stents without drugs were implanted in porcine coronary arteries (stent/artery approx. 1.1) and evaluated 4 weeks later. RESULTS: The vessel size and the stent-to-artery ratio were similar between the groups. However, at 4 weeks, the paclitaxel group had significantly reduced in-stent restenosis compared with the controls (51 +/- 27 versus 27 +/- 27% diameter stenosis, P < 0.05 and 669 +/- 357 versus 403 +/- 197 microm neointimal thickness, P < 0.05). This study further confirmed the biocompatibility of the polymer, with no foreign body reaction in any of the groups. CONCLUSIONS: This study shows that the paclitaxel-coated stents significantly reduced in-stent restenosis without eliciting inflammation.     

Experimental Evaluation of a New Single Wire Tantalum Coil Coronary Stent (Wiktor-iª)

To improve scaffolding properties, a new more densely woven Wiktor stent, the Wiktor-ia stent, was developed. Although the metal coverage remains still low compared to other stents, increased metal/vessel area raises the concern of increased thrombogenicity and neointimal hyperplasia. In this study we evaluated the Wiktor-i stent in a porcine peripheral and coronary model and compared the thrombogenicity and neointimal hyperplasia with the Wiktor-GX coronary stent. In a first study, a Wiktor-i and a Wiktor-GX coronary stent were implanted symmetrically in a preselected side branch of the right and left iliac artery of 10 healthy pigs. Quantitative vessel analysis showed comparable data before, immediately after and at follow-up. Hyperplasia measured by morphometry was also comparable in both groups (Wiktor-GX: 1.43 mm2 vs. Wiktor-i: 1.17 mm2, NS). Also, area stenosis was very similar (Wiktor-GX: 32% vs. Wiktor-i: 29%, NS). In a second study, 20 Wiktor (Wiktor-i: n=10, Wiktor-GX: n=10) coronary stents were implanted in the right coronary artery of 20 healthy pigs. Quantitative coronary analysis before, immediately after and at follow-up was comparable in both stents. The hyperplasia measured morphometrically was also comparable in both stents. (Wiktor-GX: 1.51 +/- 0.47 mm2 vs. Wiktor-i: 1.46 +/- 0.66 mm2, NS). Also the area stenosis was not significantly different (Wiktor-GX: 31% vs. Wiktor-i: 35%). In conclusion, this study shows that the increased metal/vessel area of the Wiktor-i stent does not result in an increased neointimal hyperplasia. Both stents show to be very biocompatible when implanted in porcine coronary and peripheral vessels.     

Intravascular ultrasound and quantitative coronary angiography assessment of late in-stent restenosis: in vivo human correlation and methodological implications.

Quantitative coronary angiography (QCA) is routinely used for assessment of strategies aimed at reducing in-stent restenosis. Yet QCA enables only the measurement of luminal variation of stented segments and, unlike intravascular ultrasound (IVUS), provides only an indirect estimation of late in-stent neointimal formation, which has a key role in the process of in-stent restenosis. The aims of the present study were to correlate the IVUS measurement of in-stent intimal hyperplasia (IH) with QCA indexes of restenosis, to find out whether QCA is an adequate surrogate of IVUS, and, using either QCA and IVUS data, to define the sample sizes needed to demonstrate the effectiveness of strategies to reduce in-stent restenosis. The database of the European Imaging Laboratory was used to screen 154 stents implanted between 1997 and 2001 and studied by IVUS at 6 +/- 1 months of follow-up. All cases underwent serial QCA assessment (preintervention, postintervention, and follow-up). Only 131 cases with single stent implantation in native coronary arteries were included in the study. Stent restenosis, defined as percent diameter stenosis (DS) > 50%, was present at QCA in 69 out of 131 cases (53%). Linear regression analyses were performed to correlate the amount of IH, calculated by IVUS as the average of all cross-section areas (CSA; mean % IH CSA) and QCA indexes of restenosis (late loss and % DS). A positive significant correlation was found between IVUS mean % IH CSA and QCA % DS (r = 0.74; P < 0.0001) and between IVUS mean % IH CSA and QCA late loss (r = 0.72; P < 0.0001). Based on IVUS measurements of mean % IH CSA, a total sample size of 74 stents would be required in a two-arm comparison to have 0.80 power to detect at 0.05 significant level a 30% difference between two compared groups. Alternatively, adopting the QCA late loss, 230 stents would be required. QCA measurements of late in-stent restenosis are well correlated with IVUS calculation of in-stent neointimal formation. IVUS assessment of IH allows smaller sample sizes than QCA to document significant reductions of in-stent restenosis. Therefore, the use of IVUS should be encouraged in comparison studies aimed at revealing significant neointimal differences in small sample size populations.     

A novel platinum-iridium, potentially gamma radioactive stent: evaluation in a porcine model.

In-stent restenosis (ISR) is a major problem within stented arteries. Surface treatment of stents with platinum and gold were found to have the maximum charge with least neointima formation (NF). This study was designed to evaluate platinum (maximum electrical charge) as a material to make stents to reduce NF. Iridium was added to make an alloy suitable for stent manufacture, with the potential to make the stent radioactive. We implanted the novel platinum-iridium (PI) stent in 10 porcine coronaries and compared to the Palmaz-Schatz (PS) stent implanted in 8 coronary arteries. Six weeks after implantation, angiography of the stented vessel was performed before sacrifice. The coronaries were perfusion-fixed and stained, and vessel parameters were analyzed by computer-aided histomorphometry. The thrombus formation and the inflammatory response was less in the PI stent (0.04 +/- 0.1 vs. 0.24 +/- 0.2, P = 0.005; and 1.1 +/- 0.5 vs. 2.4 +/- 0.3, P < 0.001). The NF from PI-stented arteries was smaller in size than the PS controls (1.9 +/- 0.6 mm(2) vs. 2.4 +/- 0.4 mm(2), P = 0.06). However, PI stents presented with higher recoil than the PS stent (16% vs. 5%, P < 0.001). Platinum-iridium is a highly biocompatible material with high performance, low inflammatory response with small NF. This stent does not lead to thrombus formation and has the potential (due to the presence of iridium) to be irradiated to form a gamma radioactive stent. Cathet. Cardiovasc. Intervent. 51:364-368, 2000.     

Effects of beta-radiation using a holmium-166 coated balloon on neointimal hyperplasia in a porcine coronary stent restenosis model.

Brachytherapy is a promising method of preventing and treating coronary stent restenosis. The present study was designed to observe the therapeutic effects of a radioactive balloon loaded with Holmium-166 ((166)Ho) in a porcine coronary stent restenosis model. A radioisotope of (166)Ho was coated onto the balloon surface using polyurethane (20 Gy at 0.5 mm depth). Stent overdilation injuries were induced in 2 coronary arteries in each pig (n=8). Four weeks after the injury, control balloon dilation was performed in one coronary artery (Group I) and radiation therapy using the (166)Ho coated balloon in the other coronary artery (Group II) in each pig. Follow-up coronary angiography and histopathologic assessment were performed at 4 weeks after the radiation therapy or the control balloon dilations. With regard to complete blood cell counts, liver function tests, lipid profiles and coagulation tests, there were no differences between the baseline and after radiation. On quantitative coronary angiographic analysis, reference and target artery diameter showed no differences between the 2 groups before, or 4 and 8 weeks after stenting. On histopathologic analysis of groups I and II, the injury score was 1.34+/-0.09 and 1.32+/-0.10, the area of internal elastic lamina was 4.99+/-0.17 mm(2) and 4.82+/-0.20 mm(2), and the luminal area was 3.20+/-0.10 mm(2) and 3.45+/-0.14 mm(2), respectively (p=NS). The neointimal area was 1.78+/-0.11 mm(2) in group I and 1.36+/-0.12 mm(2) in group II (p=0.017), and the histopathologic area of stenosis was 35.1+/-1.6% in group I and 27.6+/-1.9% in group II (p=0.005). In conclusion, beta-radiation of the stented porcine coronary artery using a radioactive (166)Ho coated balloon inhibited stent restenosis without any side effects.     

Particle debris from a nanoporous stent coating obscures potential antiproliferative effects of tacrolimus-eluting stents in a porcine model of restenosis.

Polymer stent coatings may not be suitable for drug elution because of inherent proinflammatory effects. A previous study suggested a beneficial effect of a stent eluting tacrolimus from a nanoporous ceramic aluminum oxide coating in a rabbit restenosis model. We investigated whether this stent is effective in preventing in-stent restenosis in a porcine restenosis model. Thirty-four juvenile swine underwent balloon overstretch injury and were subjected to implantation of either stainless steel (bare) stents, bare stents coated with nanoporous aluminum oxide alone, and coated stents eluting 50 and 180 mug of tacrolimus (FK506). In-stent restenosis was quantified at 1 and 3 months after stent placement by histomorphometry. A significant increase of neointimal hyperplasia was noted with the stents coated with aluminum oxide alone compared with bare stents (2.92 +/- 1.02 and 1.38 +/- 0.51 mm(2), respectively; P < 0.02). In all arteries containing coated stents, particle debris was found in the media and neointima, resulting in augmented vascular inflammation. In the group of stents coated with aluminum oxide, FK506 elution at a dose 180 mug reduced neointimal hyperplasia vs. no drug elution (1.66 +/- 0.49 vs. 2.92 +/- 1.02 mm(2); 180 mug vs. ceramic alone; P < 0.03). At a dose of 50 mug stent-based delivery of FK506, no reduction of neointimal hyperplasia was found (2.88 +/- 1.31 and 2.92 +/- 1.02 mm(2), respectively; P = NS; FK506 vs. ceramic alone). In summary, particle debris shed from a drug-eluting aluminum oxide coating of a stainless steel stent counteracts potential antiproliferative effects of stent-based tacrolimus delivery in a porcine model of restenosis. We propose that stent coatings eluting drugs need to be routinely tested for being tightly anchored into the stent surface. Alternatively, omission of any coating used as a drug reservoir may eliminate inflammatory particle debris after placement of drug-eluting stents.     

Zotarolimus-eluting stents reduce experimental coronary artery neointimal hyperplasia after 4 weeks.

AIMS: The addition of drug elution to coronary stents plays an integral role in coronary restenosis prevention. The present study was undertaken to determine the mechanism of action and the in vitro and in vivo efficacy of zotarolimus, a new chemical entity designed specifically for elution from phosphorylcholine (PC)-coated stents, for the reduction of neointimal hyperplasia in porcine coronary arteries. METHODS AND RESULTS: In vitro studies of Zotarolimus bound to FKBP-12 potently inhibited smooth muscle cells (SMCs) and endothelial cell (EC) proliferation. Twenty PC-only and 20 stents eluting zotarolimus 10 microg/mm were implanted in the coronary arteries of 20 domestic juvenile swine. After 28 days, zotarolimus stents exhibited less area stenosis (22.4+/-8.6 vs. 35.7+/-13%, P = 0.01), less neointimal area (1.69+/-0.55 vs. 2.78+/-1.07 mm(2), P = 0.01), less neointimal thickness (0.25+/-0.07 vs. 0.38+/-0.13 mm, P = 0.01), and greater lumen area (6.07+/-1.39 vs. 5.02+/-1.3 mm2, P = 0.01). All arteries in both the polymer-only and polymer/drug stent showed near-complete healing and minimal toxicity. Zotarolimus did not affect the extrastent segments nor alter the overall artery size (external elastic lamina cross-sectional area 9.18+/-1.19 vs. 9.06+/-1.28 mm2, P = 0.7). CONCLUSION: Zotarolimus binds to FKBP-12 and in vitro inhibits SMC and EC proliferation. Zotarolimus applied to PC-coated stents reduces neointima in the swine coronary model after 28 days. These results suggest potentially promising human clinical application for coronary stenting with this polymer/drug combination.     

Immediate changes in stenosis geometry following stent implantation: comparison between a self-expanding and a balloon-expandable stent

The immediate changes in stenosis geometry following Wallstent and Wiktor stent implantation in native coronary arteries were compared in 92 patients (46 in each group) using automated edge detection. Patients with comparable baseline stenosis characteristics were selected. Lesions were matched for lesion site, reference diameter, and minimal luminal diameter. In both groups, the stented coronary artery was the left anterior descending artery in 27 patients (59%), the left circumflex artery in four patients (9%), and the right coronary artery in 15 patients (33%). The baseline reference diameter was 2.86 +/- 0.39 mm and 2.87 +/- 0.42 mm in the Wallstent and Wiktor stent study group, respectively (NS). The baseline minimal luminal diameter was identical in both groups (1.13 +/- 0.24 mm). The nominal size (mean +/- SD) of the unconstrained Wallstent was 3.5 +/- 0.3 mm and 3.3 +/- 0.3 mm for the Wiktor stent (P less than 0.05). Both types of stents resulted in a similar increase in minimal luminal diameter immediately following implantation (Wallstent: 2.34 +/- 0.38 mm, Wiktor stent: 2.43 +/- 0.27 mm, NS). Furthermore, there was a similar decrease in diameter stenosis and increase in minimal luminal cross-section area following implantation of both stents. These morphological changes were associated with a normalization of the hemodynamic parameters in both groups. It is concluded that, although the Wallstent and Wiktor stent are different in design and mechanical characteristics, there is a similar immediate improvement in stenosis geometry following implantation of both devices.     

Heparin-coated Wiktor stents in human coronary arteries (MENTOR trial). MENTOR Trial Investigators

The purpose of this study was to determine the feasibility, safety, and efficacy of elective stenting with heparin-coated Wiktor stents in patients with coronary artery disease. In experimental studies, heparin coating has been shown to prevent subacute thrombosis and restenosis. Recently, a new method of heparin coating was developed, resulting in a more stable and predictable heparin layer on stent devices. This trial constitutes the first in-human use of this coating procedure, applied on the well-known Wiktor stent device. Heparin-coated Wiktor stent implantation was performed in 132 consecutive patients (132 lesions) in a multicenter international trial from September 1996 to February 1997. Forty-three percent of patients had unstable angina, 33% had previous myocardial infarction, and 10% had diabetes mellitus. Patients were followed for 12 months for occurrence of major adverse cardiovascular events, and 96% of the eligible patients underwent quantitative angiographic control at 6 months. Stent deployment was successful in 95.5% of lesions. Minimal lumen diameter increased by 1.67 +/- 0.48 mm (from 1.02 +/- 0.38 mm before to 2.69 +/- 0.37 mm after the stent implantation). Mean percent diameter stenosis decreased from 67.4 +/- 11.3% before to 18.9 +/- 7.7% after the intervention. A successful intervention (<50% diameter stenosis and no major adverse cardiac events within 30 days) occurred in 97% of the patients. The subacute thrombosis rate was 0.8%, which compares favorably with historical controls of this stent, and a low incidence of postprocedural increase in creatine kinase-MB was noted. At 6 months, event-free survival was 85% and angiographic restenosis rate was 22% with late loss of 0.78 +/- 0.69 mm and a loss index of 0.48 +/- 0.44. Heparin-coated Wiktor stents appeared to be an efficacious device to treat Benestent-like lesions, yielding angiographic and clinical results comparable to a heparin-coated Palmaz-Schatz stent. Despite its use in more complex lesions, the incidence of subacute thrombosis appeared to be lower than historical controls with a similar noncoated stent.     

Experimental Evaluation of a New Tubular Coronary Stent (V-Flexª)

The safety, efficacy, angiographic and histological effects of a new 316 L, SS seamless stainless steel tubular stent (V-Flexa, Global Therapeutics, Broomfield, Colorado) was evaluated in a porcine coronary and peripheral artery model. Implantation in the right coronary artery was successful in all 16 pigs. Eight pigs were angiographically controlled after 6 weeks and then sacrificed for morphometric analysis. All stented coronary vessels were widely patent at this moment and morphometric analysis showed only a mild fibromuscular neointimal hyperplasia resulting in a neointimal hyperplasia of 1.15 +/- 0.38 mm2. The remaining 8 pigs were controlled and sacrificed at 12 weeks. At that time, all stented vessels were patent and neointimal hyperplasia was 1.22 +/- 0.34 mm2. Comparison with the Palmaz-Schatza coronary stent (Cordis, Miami, Florida) in a porcine peripheral artery model demonstrated significantly less neointimal hyperplasia at 6 weeks (1.11 +/- 0.73 vs. 2.40 +/- 0.36, p = 0.001) and at 12 weeks (1.53 +/- 0.42 vs. 2.47 +/- 0.63, p = 0.003) for the V-Flex stent. In conclusion, V-Flex coronary stent implantation in a porcine coronary and peripheral arteries results in a high procedural success rate without subacute thrombotic occlusions, despite no further anticoagulation nor antiplatelet therapy. Six and 12 week histopathological and morphometric evaluation demonstrated only a mild fibromuscular neointimal hyperplasia. Comparison with the Palmaz-Schatz coronary stent in a peripheral artery model showed significantly less neointimal hyperplasia in the V-Flex stent.     

Effect of amlodipine on vascular responses after coronary stenting compared with an angiotensin-converting enzyme inhibitor.

BACKGROUND: Prevention of restenosis after coronary stenting is clinically important. We compared amlodipine and quinapril to determine which is more effective in preventing restenosis after stenting. METHODS AND RESULTS: Immediately after successful coronary stenting of 101 lesions in 63 consecutive patients, the patients were randomly divided into 2 groups: 32 patients with 48 lesions were administered amlodipine 5 mg/day (group A), and 31 patients with 53 lesions were administered quinapril 10 mg/day (group Q). Lesions were assessed by quantitative coronary angiography (QCA) before and immediately after stenting and in the follow-up phase. Intravascular ultrasound (IVUS) could only be performed on 20 lesions in group A and 16 lesions in group Q throughout the follow-up period. We analyzed each lesion at 5 sites. In the follow-up phase, the minimal lumen diameter in group A was significantly larger than that in group Q (1.88 +/- 0.64 mm vs 1.52 +/- 0.53 mm, p<0.01). In the follow-up phase, the neointimal area (stent area-lumen area) in group A was significantly smaller than that in group Q (1.9 +/- 0.5 mm2 vs 2.7 +/- 0.8 mm2 at the middle portion of stent, p<0.01). CONCLUSION: These QCA and IVUS findings suggest that amlodipine has beneficial effects in inhibiting neointimal hyperplasia in stented lesions compared with quinapril.     

Histopathological findings of new in-stent lesions developed beyond five years.

We analyzed 14 cases of new lesions inside implanted bare-metal stents. In every case, there was no angiographic restenosis within 3 years, but a new lesion was observed inside a stented segment at long-term follow-up (>5 years). Fourteen cases were evaluated: 9 with Wiktor stents, 2 with Palmaz-Schatz stents, and 3 with ACS Multilink stents. The interval from stent implantation to follow-up angiography was 63-147 months (89 +/- 23). Thirteen lesions were treated by percutaneous coronary intervention (PCI) and stenotic tissue was obtained by directional coronary atherectomy (DCA) in 10 cases. All retrieved samples were composed of newly developed atherosclerosis facing the healed neointimal layer, and four samples showed histopathological findings of acute coronary syndrome. Stent struts were retrieved in four cases and no inflammation was observed surrounding them. Qualitative and quantitative analysis of stent struts was performed in two cases that showed no metal corrosion. These findings suggest that new atherosclerotic progression occurred inside the implanted stent without peristrut inflammation.     

The clinical results of a platelet glycoprotein IIb/IIIa receptor blocker (abciximab: ReoPro)-coated stent in acute myocardial infarction.

OBJECTIVES: This study is a prospective randomized trial investigating clinical outcomes of patients with acute myocardial infarction (AMI) treated with abciximab (ReoPro)-coated stents. BACKGROUND: Recently we have demonstrated that abciximab-coated stents have inhibitory effects in the prevention of coronary restenosis. METHODS: Ninety-six patients with AMI were randomly allocated into two groups; group I received abciximab-coated stents (n = 48, 57.1 +/- 12.0 years), and group II received bare metal control stents (n = 48, 58.4 +/- 11.6 years). RESULTS: At baseline, clinical characteristics, percent diameter stenosis, and minimal luminal diameter were no different between the two groups. One patient in group II had reinfarction and target lesion reintervention during hospital stay. Follow-up coronary angiography was obtained in 77.1% (37 of 48) in group I and 75.0% (36 of 48) in group II. Percent diameter stenosis and late loss were significantly lower in group I than group II (18.9 +/- 5.54% vs. 37.9 +/- 6.25%, p = 0.008; and 0.39 +/- 0.29 mm vs. 0.88 +/- 0.45 mm; p = 0.008, respectively). At follow-up intravascular ultrasound, intrastent lumen area and intrastent neointimal hyperplasia (NIH) area were 5.4 +/- 1.8 mm2 and 2.2 +/- 1.5 mm2, respectively, in group I and 4.3 +/- 1.6 mm2 and 3.4 +/- 1.8 mm2, respectively, in group II (p = 0.045). And, in-stent restenosis rate was lower in group I than group II (p = 0.011 and p = 0.008, respectively). During 1-year follow-up, two patients in group II (4.1%) had AMI, whereas no patient in group I suffered AMI. Target lesion revascularization and total major adverse cardiac events rates were relatively lower in group I compared with those in group II (10.4% [5 of 48] vs. 20.8% [10 of 48], p = 0.261, and 10.4% vs. 25.0%, p = 0.107, respectively). CONCLUSIONS: Abciximab-coated stent implantation was safe and effective without stent thrombosis in AMI patients.     

Restenosis after stenting of matched occluded and non-occluded coronary arteries. Should there be a difference?

AIMS: It is not known whether the higher restenosis rates reported after balloon angioplasty of occluded as opposed to non-occluded coronary arteries are still found after placement of coronary stents in lesions matched for factors known to affect late angiographic outcome. METHODS AND RESULTS: In a retrospective analysis of 1276 patients who had undergone coronary stent placement and in whom 6-month angiographic follow-up was available, we identified 144 patients with a total coronary occlusion which matched a non-occluded coronary lesion in another 144 patients. Matching lesion pairs were of the same type (de novo or restenotic), were supplied with the same type of stent, had reference vessel diameters identical within 0.3 mm and stented vessel segment lengths identical within 8 mm, and were located in corresponding target vessels. After stenting, statistically identical minimal lumen diameters had been achieved in both groups (occluded: 2.74+/-0.35 mm, non-occluded: 2. 77+/-0.32 mm, P = 0.45). At follow-up, minimal lumen diameters were not different (occluded: 1.65+/-0.77 mm, non-occluded: 1.76+/-0.76 mm, P = 0.24), reflecting an identical late lumen loss for occlusions (1.09+/-0.76 mm) and non-occluded lesions (1.01+/-0.70 mm, P = 0.38). Because of the significantly larger acute gain, the loss index was significantly lower for occluded vessels (0.40+/-0.27 vs 0. 51+/-0.35, P = 0.003). Corresponding restenosis rates were 33% (occluded) and 28% (non-occluded;P = 0.44). For stented vessel segment lengths >18 mm, restenosis rates were markedly higher (occluded: 42%, non-occluded: 36%) than for stented vessel segment lengths 相似文献   

Experimental efficacy of an everolimus eluting cobalt chromium stent.

INTRODUCTION: Rapamycin and its analogs are now being coated on different stent platforms, using different polymer matrices to prevent restenosis by impairing vascular smooth muscle cell proliferation and neointimal formation. METHODS: We evaluated the feasibility and compared the efficacy of biostable polymeric everolimus and sirolimus (CYPHER, Cordis) eluting stents in a porcine coronary model. Cobalt chromium balloon expandable stents (ML VISION, Guidant) were coated with a polymer containing everolimus (190 mug/cm(2)). Twelve pigs underwent placement of 36 oversized sirolimus (n = 12), everolimus (n = 12), and bare metal (cobalt chromium, n = 12) stents in the coronary arteries. RESULTS: At day 28, vessel injury scores were low (<0.25) and similar between each of the three test groups. The mean neointimal thickness was significantly lower in the everolimus- (0.13 +/- 0.07 mm, P = 0.02) and sirolimus-eluting stents (0.13 +/- 0.08 mm, P = 0.04) versus the bare metal stents (0.20 +/- 0.07 mm). The mean percent area stenosis was similar for the everolimus-eluting stents [(20.8 +/- 6.9)%] and the sirolimus-eluting stents [(20.8 +/- 7.6)%], and each was significantly less than that of bare metal stents [(26.1 +/- 7.8)%, P = 0.05]. CONCLUSION: Stent-based delivery of sirolimus and everolimus delivered via durable polymeric matrices are equally effective in the suppression of neointimal formation at day 28 in the porcine coronary model. Further study is necessary to document dose response and long-term comparative effects of these drug-eluting stents.