雷帕霉素-巴曲酶复合药物涂层支架预防支架内再狭窄的实验研究

目的评价雷帕霉素-巴曲酶复合药物涂层支架对再狭窄和支架内血栓的防治作用及安全性,减少术后抗血小板药物的应用及并发症的发生率。方法采用随机、双盲试验在16头微型猪的冠状动脉前降支或左旋支分别置入支架1枚,其中雷帕霉素涂层支架（每枚支架药物剂量1.2μg/mm2）共8枚,为对照组;雷帕霉素-巴曲酶复合药物涂层支架（每枚支架含雷帕霉素1.2μg/mm2、巴曲酶0.3μg/mm2）共8枚,为实验组。对照组术前3 d起每天口服氯吡格雷75 mg和阿司匹林0.3 g直至28 d处死;实验组术前3 d至术后7 d每天口服氯吡格雷75 mg和阿司匹林0.3 g,此后改为每天口服阿司匹林0.3 g,直至28 d处死。28 d时进行冠状动脉造影随访,术后处死动物,取出支架血管,进行组织学分析。结果再狭窄率:对照组为0,实验组为0。管腔丢失率:对照组为（7±5）%,实验组为（4±3）%。新生内膜面积:对照组为（1.0±0.8）mm2,实验组为（0.9±0.7）mm2。结论雷帕霉素-巴曲酶复合药物涂层支架与单纯雷帕霉素涂层支架比较可以减少支架置入术后的口服氯吡格雷总量及用药时间。     

雷帕霉素-替罗非班复合药物涂层支架预防支架内血栓和再狭窄的实验研究

目的探讨雷帕霉素-替罗非班复合药物涂层支架预防支架内血栓和再狭窄的疗效及机制。方法8只小型猪随机分为单纯雷帕霉素涂层支架（RES）组和雷帕霉素-替罗非班复合药物涂层支架（RTES）组,每只动物于冠状动脉中置入支架2枚。术后RES组服用阿司匹林300 mg/d和氯吡格雷75 mg/d,3个月;RTES组服用阿司匹林300 mg/d,3个月,氯吡格雷75 mg/d,1个月。实验期间对动物行为学和出凝血障碍等并发症进行观察。3月后复查冠状动脉造影,处死动物,取出支架血管段,行组织病理学分析。结果①两组均未发现急性、亚急性和远期血栓,无出凝血等并发症发生。②支架部位血管腔面积:雷帕霉素涂层支架组为（4.89±0.46）mm2,雷帕霉素-替罗非班复合涂层支架组为（4.96±0.35）mm2;新生内膜面积:雷帕霉素涂层支架组为（1.05±0.09）mm2,雷帕霉素-替罗非班复合涂层支架组为（1.12±0.10）mm2;管腔面积丢失率:雷帕霉素涂层支架组为（21±7）%,雷帕霉素-替罗非班复合药物涂层支架组为（19±9）%。结论①雷帕霉素-替罗非班复合药物涂层支架可有效预防PC I术后支架内血栓形成。②雷帕霉素-替罗非班复合药物涂层支架防治支架内再狭窄的疗效与单纯雷帕霉素支架无差异。     

应用雷帕霉素药物涂层支架治疗冠脉支架内再狭窄研究

目的 :评价雷帕霉素药物涂层支架 (CYPHERCordis)治疗冠脉支架内再狭窄的临床效果。方法 :我院在 2 0 0 2年 10月至 2 0 0 3年 10月对 2 1例冠心病冠脉支架内再狭窄患者置入CYPHERTM支架(Cordis)治疗 ,对 16例前降支支架内再狭窄患者置入CYPHER支架 16个 ,4例右冠支架内再狭窄患者置入CYPHER支架 4个 ,1例回旋支支架内再狭窄患者置入CYPHER支架 1个。观察药物涂层支架的手术成功率 ,术中并发症 ,住院期间及 2 14个月随防期间的心绞痛、心肌梗塞、猝死 ,再次血运重建等发生情况。结果 :手术即刻成功率 10 0 % ,术后造影病变残余狭窄率为 5 %± 3 5 % ,支架完全覆盖病变 ,支架近远段无新夹层 ,血流TIMI3级 ,临床随访 2～ 14个月 2 1例心绞痛消失 ,其中 12例 6～9个月 ,复查冠脉造影 ,无支架内再狭窄发生。结论 :雷帕霉素药物涂层支架 (CYPHER) ,治疗冠脉支架内再狭窄是安全有效的 ,短期临床随访结果明显优于单纯再次扩张及首次置入普通支架的临床效果     

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。     

雷帕霉素-缬沙坦复方药物洗释支架预防支架内再狭窄的实验研究

目的　探讨雷帕霉素 -缬纱坦复方药物洗释支架 (复方药物洗释支架 )对支架植入术后再狭窄的预防作用。方法　对 2 2只雄性新西兰白兔进行腹主动脉拉伤后分别植入复方药物洗释支架 (复方组 )和普通支架 (裸支架组 )各 11只。两组均在术后 8周行血管内超声检查和腹主动脉行造影检查。结果　支架部位血管腔面积裸支架组小于复方组 (P <0 0 1)、支架内增生内膜面积及内膜增生程度裸支架组大于复方组 (P <0 0 0 1)。结论　复方药物洗释支架在动物实验中具有明显预防支架内再狭窄的作用     

雷帕霉素和甲氨蝶呤涂层支架预防支架内再狭窄的实验研究

目的　评价雷帕霉素涂层支架、甲氨蝶呤涂层支架以及雷帕霉素和甲氨蝶呤混合涂层支架抑制血管新生内膜的作用和预防支架内再狭窄的有效性。方法　本实验采用随机、双盲试验 ,在2 5头微型猪的冠状动脉前降支或左旋支分别置入支架 1枚 ,其中金属裸支架 8枚、甲氨蝶呤涂层支架(每枚支架药物剂量 2 5 0～ 30 0 μg) 5枚、雷帕霉素涂层支架 (每枚支架药物剂量 6 8～ 96 μg) 7枚、雷帕霉素和甲氨蝶呤混合涂层支架 (每枚支架含雷帕霉素 5 8～ 81μg、甲氨蝶呤 12 0～ 170 μg) 5枚。 2 8d后进行冠状动脉造影随访 ,术后处死动物 ,取出支架血管 ,进行组织学分析。结果　再狭窄率 :对照组为2 5 % ( 2 8) ,甲氨蝶呤组为 80 % ( 4 5 ) ,其余 2组为 0。平均狭窄程度 :对照组为 31%± 2 2 % ,甲氨蝶呤涂层支架组为 6 4 %± 2 5 % (P <0 0 5 ) ,雷帕霉素涂层支架组为 8%± 17% (P <0 0 5 ) ,雷帕霉素和甲氨蝶呤混合涂层支架组为 3%± 4 % (P <0 0 5 )。新生内膜面积 :对照组为 ( 2 18± 1 0 3)mm2 ,甲氨蝶呤涂层支架组为 ( 3 93± 1 4 8)mm2 (P =0 0 6 9) ;雷帕霉素涂层支架组为 ( 0 94± 0 88)mm2 (P <0 0 5 ) ,雷帕霉素和甲氨蝶呤混合涂层支架组为 ( 0 4 7± 0 2 4 )mm2 (P <0 0 5 )。结论　在本实验中     

雷帕霉素涂层支架对支架内早期再狭窄的预防

目的 :评价乳酸和乙醇酸聚合物携带雷帕霉素并以支架为载体抑制血管新生内膜的作用和预防支架内再狭窄的有效性。方法 :采用随机、双盲试验 ,在 2 0头微型猪的冠状动脉前降支或左旋支分别置入支架 1枚 ,其中金属裸支架 8枚 ;雷帕霉素涂层支架 12枚。涂层材料选用乳酸和乙醇酸聚合物 ,根据两种材料比例将涂层支架分为雷帕霉素缓慢释放涂层支架 (药物剂量 6 5～ 90 μg/支架 ,5枚 )和雷帕霉素快速释放涂层支架 (药物剂量 6 8～ 96 μg/支架 ,7枚 )。2 8d后进行冠状动脉造影 ,术后处死动物 ,取出支架血管 ,进行组织学分析。 结果 :对照组的再狭窄率为 2 5 .0 % (2 /8) ;两组雷帕霉素涂层支架均为 0 %。平均狭窄程度 :对照组为 (31± 2 2 ) % ,雷帕霉素缓慢释放涂层支架组减少了 2 8% (P <0 .0 5 ) ;雷帕霉素快速释放涂层支架组减少了 2 3% (P <0 .0 5 ) ;新生内膜面积 :对照组 (2 .18± 1.0 3)mm2 ;雷帕霉素缓慢释放涂层支架组减少了 1.0 9mm2 (P <0 .0 5 ) ;雷帕霉素快速释放涂层支架组减少了 1.2 4mm2 (P <0 .0 5 )。结论 :乳酸和乙醇酸聚合物携带雷帕霉素涂层支架可以降低支架内的狭窄程度 ,有效地减少血管内新生内膜面积 ,预防支架内的狭窄     

雷帕霉素涂层支架预防血管内再狭窄的研究进展

如何防治冠状动脉介入治疗术后再狭窄形成已成为当今介入心脏学界面临的一大挑战 ,近年来的研究表明雷帕霉素涂层支架可有效预防再狭窄形成 ,为解决这一难题提供了新的治疗手段。本文就目前雷帕霉素涂层支架在临床防治再狭窄研究的最新进展作一综述。     

抗增殖药物涂层支架预防和治疗支架内再狭窄的临床研究进展

支架内再狭窄是介入治疗中的难题。新近多个有关雷帕霉素、紫杉醇涂层支架的临床试验显示药物涂层支架能有效预防支架内再狭窄。其对复杂病变的疗效有待于进一步研究。     

雷帕霉素涂层支架预防再狭窄的进展

冠状动脉内支架植入术在经皮治疗冠状动脉粥样硬化性心脏病中已成为最普遍的技术，其数量在世界范围内已超过整个经皮冠状动脉内手术的75％。尽管支架植入比球囊成形可降低再狭窄的发生，但仍有15％～35％的病例发生支架内再狭窄…。所以，需要一个有效的预防和治疗手段来防治支架内再狭窄。     

Stent design-related coronary artery remodeling and patterns of neointima formation following self-expanding and balloon-expandable stent implantation.

The self-expanding Wallstent (WS) and balloon-expandable Palmaz-Schatz stents (PS) display different mechanical and dynamical stent properties. We analyzed the impact of the respective stent design on coronary wall geometry using quantitative coronary angiography (QCA) and intracoronary ultrasound (ICUS) measurements. Serial measurements were performed within the stent and within reference segments of 50 patients (25 WS, 25 PS). Relative changes for each parameter in both stent designs were calculated (Mann-Whitney U-test; 95% CI). The luminal net gain in WS was not significantly higher in WS compared with PS (1.63 +/- 1.11 vs. 1.44 +/- 0.63 mm; P = 0.2554). The respective loss indexes were also similar (0.38 +/- 0.42 vs. 0.36 +/- 0.23; P = 0.8578). The WS segments showed significant postinterventional stent expansion with positive vessel remodeling. The neointima formation was significantly higher in WS segments (4.23 +/- 2.07 vs. 2.22 +/- 2.22 mm(2)). The coronary wall morphology and stent geometry after 6.5 +/- 1.2 months are related to the stent design. In WS segments, the neointima formation was balanced by postinterventional stent expansion, resulting in a comparable relative lumen loss in both stent types. The respective stent design had no impact on the vessel reference segments.     

The genous™ endothelial progenitor cell capture stent accelerates stent re‐endothelialization but does not affect intimal hyperplasia in porcine coronary arteries

Objectives : To study the effect of endothelial progenitor cell (EPC) capture on the vascular response to coronary stenting. Background : The introduction of drug‐eluting stents has reduced the need for target lesion revascularization, but their effect on delayed healing, inflammation, and vascular dysfunction has emphasized the need to design strategies that improve current DES. One such strategy is to improve endothelialization by capturing CD34‐positive cells (EPC) by the stent surface. The first human clinical trial using coronary EPC capture stents showed stent safety but neointimal thickness (NIT) was not reduced compared to bare metal stents (BMS). To understand these responses we studied the coronary response to the EPC capture stent in swine. Methods and Results : The stent, coated with murine antihuman monoclonal CD34 antibodies, was assessed with QCA guided stent implantation in normal swine coronary arteries for early endothelialization at 2 and 5 days, and NIT at 28 and 90 days in comparison to control stents carrying a non‐specific murine antibody or to BMS. The main finding was that while the EPC capture stent significantly improved early endothelialization it did not reduce NIT at 28 and 90 days. Conclusions : The EPC capture stent improves early endothelialization in swine but this does not affect neointimal thickness as compared to control stents at 28 and 90 days. © 2011 Wiley Periodicals, Inc.     

Stent-based tempamine delivery on neointimal formation in a porcine coronary model

BACKGROUND: Tempamine is one of new class of antioxidant agents, the nitroxides, which have shown a wide range of biological effects like suppressing free radical driven reactions to maintain cell functions. The objectives of this study were to evaluate the effect of a biodegradable polymer coated stent loaded with tempamine on in-stent neointimal formation. METHODS: Stainless steel stents were dip coated in biodegradable elastomeric poly (ester-amide) (co-PEA) or in polymer solution mixed with 50% (wt%) and 100% (wt%) tempamine. One group 100% (wt%) tempamine loaded stents were further dip coated in co-PEA polymer to form a top layer. Stainless steel bare, polymer-only, and different doses tempanine coated stents were implanted into porcine coronary arteries with a stent to artery ratio 1.2:1. Histomorphometric analysis was performed at 5 days and 6 weeks respectively. RESULTS: Histomorphometric analysis showed that the bare, polymer-only and tempamine-coated stents elicited a similar tissue response at 5 days. At 6 weeks, the peri-strut inflammation and neointimal hyperplasia of polymer-only stents were comparable to the bare stents. Compared to the bare stents, 50% tempanine coated stents had a trend to decrease the arterial injury (0.62 +/- 0.41 versus 0.34 +/- 0.18, P = 0.075) and neointimal hyperplasia (1.80 +/- 0.77 versus 1.27 +/- 0.39 mm2, P = 0.085). However, 100% tempanine coated showed significantly increased inflammatory response and neointimal formation. CONCLUSION: These co-PEA polymer coatings showed a biocompatible performance. Loaded with 50% tempamine had a trend to decrease neointimal hyperplasia. The 100% tempamine for stent-based delivery may have potential cytotoxic effects to arterial wall. Using a co-PEA polymer topcoat could effectively abolish these side effects.     

Estrogen-eluting, phosphorylcholine-coated stent implantation is associated with reduced neointimal formation but no delay in vascular repair in a porcine coronary model.

Estrogen can inhibit intimal proliferation and accelerate endothelial regeneration after angioplasty. This suggests that estrogen may prevent in-stent restenosis. Unlike other therapies to prevent restenosis, estrogen may also not delay endothelial regrowth, thereby avoiding the risk of late stent thrombosis. The purpose of this work was to determine the effect of a 17beta-estradiol-eluting stent on neointimal formation in a porcine model. Each artery of six pigs was randomized to either a control, low-dose, or high-dose 17beta-estradiol-eluting stent. All animals were sacrificed at 30 days for histopathological analysis. There was a 40% reduction in intimal area in the high-dose stents compared with control stents (2.54 +/- 1.0 vs. 4.13 +/- 1.1 mm(2), for high dose vs. control, respectively; P < 0.05). There was complete endothelial regeneration at 30 days and similar inflammatory response to stenting on histopathology in all the stent groups. This is the first study to show that 17beta-estradiol-eluting stents are associated with reduced neointimal formation without affecting endothelial regeneration in the pig model of in-stent restenosis. Estrogen-coated stents may have a potential benefit in the prevention and treatment of in-stent restenosis.     

Neointimal response following rotational atherectomy compared to balloon angioplasty in a porcine model of coronary in-stent restenosis

In-stent restenosis remains a clinical therapeutic challenge. Rotational atherectomy (RA) is an attractive treatment option as it may cause less vascular injury than balloon angioplasty (BA) and, therefore, limit further neointimal response. In an animal model of coronary in-stent restenosis, thermal injury and stenting created neointima (old NI). The treatment of in-stent restenosis with either BA (n = 9) or RA (n = 11) also generated neointima (new NI). The average areas (mm²) of old NI in the BA and RA groups were similar (3.77 ± 0.40 vs. 3.67 ± 0.53; P = 0.32). However, new NI formed after treatment of in-stent restenosis was significantly less in the RA as compared to the BA group (0.33 ± 0.12 vs. 0.73 ± 36, P < 0.01). In this porcine coronary artery model of in-stent restenosis, treatment with rotational atherectomy resulted in significantly less recurrent neointimal hyperplasia than balloon angioplasty. This animal study, thus, provides a rationale for the clinical use of rotablation in the treatment of in-stent restenosis. Cathet. Cardiovasc. Diagn. 45:332–336, 1998. © 1998 Wiley-Liss, Inc.     

一种新型可降解聚合物涂层-雷帕霉素洗脱支架对猪冠状动脉新生内膜增生的影响

目的:评价可降解高分子材料聚丙交酯-乙交酯(PLGA)作为支架药物载体的可行性及携带雷帕霉素的PLGA涂层支架的抗内膜增生作用。方法:在14头微型猪的3支冠状动脉分别植入钴铬合金裸支架(CoCr-BMS)、不载药的PLGA涂层支架(PCOS)和PLGA涂层雷帕霉素洗脱支架(PLGA-SES)。分别在支架植入后1个月和3个月时,复查冠状动脉造影,然后分离支架段血管行组织病理学分析。结果:共有12头动物存活,其余2头动物可能因麻醉剂相关的呼吸抑制而死亡。支架植入后1个月和3个月,不载药的PLGA涂层支架新生内膜面积和晚期管腔丢失与CoCr-BMS组相近,而PLGA-SES组则明显低于CoCr-BMS组。组织形态学示3组支架段血管损伤积分、炎症积分及再内皮化积分差异无统计学意义。结论:在猪冠状动脉支架模型中,PLGA涂层的支架设计具有良好的生物相容性和安全性;携带雷帕霉素的这种支架可抑制新生内膜形成,预防支架再狭窄的发生。     

Comparative study of tacrolimus and paclitaxel stent coating in the porcine coronary model

SummaryBackground Tacrolimus is a potent antiproliferative and immunosuppressive agent allowing for improved endothelial regeneration. The aim of our study was the preclinical evaluation of tacrolimus in a drug eluting nonerodable polymer stent system and its comparison with paclitaxel.Methods and results A total of 40 domestic pigs and 10 mini-pigs underwent coronary stenting with a follow-up time between 6 hours and 3 months. Stents were implanted in coronary arteries with an overstretch ratio of 1.2. After 3 days, a 1.73 μg/mm² coating produced tacrolimus tissue levels of 20 μmol/l in the coronary artery wall. Effective tissue concentrations were sustained for 28 days. Based on histomorphometric analysis, tacrolimus stent treated vessels had a reduced extent of neointima formation compared with controls at 28 days (–51% compared to control) but not at 3 months. High dose paclitaxel stent coating (1.44 μg/mm²) was complicated by unexpected deaths of pigs and thrombotic stent occlusion at control angiography. Long-term porcine data showed no persistent inhibition of neointimal growth by paclitaxel and tacrolimus stent coating.Conclusions Similar to paclitaxel, tacrolimus stent coating reduces neointimal proliferation in the porcine coronary model. However, dosing and long-term efficacy remains a critical issue in stent-based local drug delivery.