聚乳酸聚碳酸酯共聚物涂层紫杉醇洗脱支架预防小型猪血管支架内再狭窄的实验研究

目的评价生物可降解聚乳酸聚碳酸酯共聚物(PTDLA)涂层紫杉醇洗脱支架预防小型猪血管支架内再狭窄的有效性与安全性。方法 27只小型猪以体质量编号随机分入裸支架(BMS)组、单纯PTDLA涂层支架(POLY)组和PTDLA涂层紫杉醇洗脱支架(PACL)组。各组均包括1、3个月和6个月观察终点的小型猪各3只。每只小型猪于双侧股动脉各置入同种支架1枚。至观察终点,复查血管造影并处死取材,通过组织病理形态学观察内膜增生及炎症情况。结果共54枚支架成功置入27只小型猪股动脉,术后均健康存活。术后即刻及处死前血管造影示各相关动脉均通畅,无支架内血栓、移位及其他并发症。1个月时,3组中PACL组内膜厚度最小[(133±26)μm比(280±54)μm和(284±46)μm,P<0.05];管腔面积最大[(3.92±0.32)mm~2比(2.86±0.24)mm~2和(2.78±0.22)mm~2,P<0.05]。3个月时,3组反映内膜增生的各项指标均加重,仍以PACL组内膜厚度最小[(190±21)μm比(374±40)μm和(334±30)μm,P<0.01],管腔面积最大[(3.68±0.30)mm~2比(2.40±0.20)mm~2和(2.55±0.23)mm~2,P<0.01]。6个月时,3组内膜增生均进一步加重,PACL组内膜厚度最小,但3组间差异无统计学意义[(328±28)μm比(440±45)μm和(408±39)μm,P=0.13];剩余管腔面积最大,但差异亦无统计学意义[(2.83±0.25)mm~2比(2.17±0.23)mm~2和(2.30±0.18)mm~2,P=0.12]。结论采用可降解PTDLA涂层的紫杉醇洗脱支架可以安全有效地抑制健康小型猪血管支架置入术后1个月和3个月时的内膜增生,保持管腔面积,预防血管支架内再狭窄。     

缬沙坦涂层支架对支架术后再狭窄中胶原沉积的影响

目的评价缬沙坦涂层支架对支架置入后新生内膜中胶原沉积的影响及其预防支架内再狭窄的可行性。方法18只新西兰大白兔分为裸支架组,载体涂层支架组,缬沙坦涂层支架组3组。采用多层涂布技术制备缬沙坦涂层支架和载体涂层支架。分别将裸支架、载体涂层支架及缬沙坦涂层支架置入兔腹主动脉。术前、术后及支架置入3个月后分别行定量腹主动脉造影(QCA)测量血管直径。3个月后处死实验兔,分别测定3组支架血管段的管腔面积,内外弹力膜围绕面积,新生内膜面积及最大内膜厚度并做比较。将支架血管段进行MASSON染色,观察胶原沉积情况,天狼星红-苦味酸染色进一步观察胶原的类型。结果裸支架组(n=8),载体涂层支架组(n=8),缬沙坦涂层支架组(n=10),QCA测量的术前、术后及3个月后腹主动脉直径相似。缬沙坦组管腔面积最大,新生内膜面积最小,裸支架组、载体涂层支架组、缬沙坦涂层支架组平均管腔面积分别为(4345548±125822)μm2,(4302061±167952)μm2,(5016269±207934)μm2,平均新生内膜面积分别为(1119635±163503)μm2,(1135636±136555)μm2,(441577±74099)μm2,平均最大内膜厚度分别为(240±30)μm,(192±21)μm,(116±12)μm。MASSON染色可见新生内膜中主要是胶原沉积,天狼星红-苦味酸染色发现胶原沉积主要为Ⅲ型胶原,间或有Ⅰ型胶原。结论缬沙坦涂层支架主要是通过抑制胶原沉积抑制支架置入后血管内膜增生发挥其防治支架内再狭窄作用的。     

管形冠状动脉支架V-Flex~(TM)在猪冠状动脉和髂动脉支架模型上的实验评价

在猪的冠状动脉和周围血管支架模型上 ,通过血管造影和组织病理学检查评价一种新型的 316L不锈钢管型冠状动脉支架V -FlexTM的安全有效性。将 16个支架置入 16只猪的右冠状动脉 ,8只猪观察 6周 ,另 8只猪观察 12周。血管造影显示所有右冠状动脉通畅 ,6周时 16只猪的右冠状动脉造影定量分析显示直径狭窄平均为9% ;6周时 8只猪的组织病理学分析显示右冠状动脉内膜增生为 1.15± 0 .38mm2 ,12周时 8只猪的组织病理学分析显示内膜增生为 1.2 2± 0 .34mm2 。同Palmaz -Schatz冠状动脉支架在周围动脉上比较 ,V -FlexTM引起的内膜增生较轻 (6周 :1.11± 0 .37mm2 比 2 .40± 0 .36mm2 ;12周 :1.5 3± 0 .42mm2 比 2 .47± 0 .6 3mm2 ,P均 <0 .0 5 ) ,血管损伤、炎症反应及血栓反应亦较轻。研究结果表明 ,V -FlexTM冠状动脉支架在猪的冠状动脉和周围动脉上引起的新生内膜增生轻 ,血管损伤小 ,且炎症反应、血栓反应亦较轻 ,有较好的生物相容性     

血管内皮细胞生长因子基因涂布支架预防门腔静脉分流支架狭窄的实验研究

目的　通过转染人血管内皮细胞生长因子 (phVEGF)基因促使血管内支架处内皮细胞生长以预防支架内再狭窄的发生。方法　将 phVEGF基因局部涂布于由多聚赖氨酸包被的血管内支架上 ,采用介入方法经颈静脉插管至 6只狗的右肝静脉 ,同时以置入裸支架为对照组。结果　支架置入后第 1周 ,在转染 phVEGF基因组局部血管组织内 ,RT PCR法检测到 phVEGF的表达 ;荧光显微镜下观察到部分血管内皮细胞发出黄绿色荧光 ;扫描电镜显示支架腔内皮分化程度较对照组高。置入后第 8周 ,转染 phVEGF基因组 (n =6 )血管造影显示支架通畅 ,而对照组 (n =5 )则均发生再狭窄 ;支架端肝静脉血管平均新生内膜厚度 ,平均新生内膜面积 ,百分狭窄面积均明显小于对照组 [(0 .16 7± 0 .10 3)mm比 (1.96 5± 0 .72 5 )mm ,(2 .5 6 8± 1.5 2 6 )mm2 比 (17.5 96± 7.939)mm2 ,(11.46 2± 5 .42 3) %比 (6 8.5 0 5± 2 4.0 0 3) %,P <0 .0 5 ];免疫组化显示平滑肌细胞增殖程度 (PLI)也显著高于对照组 [(0 .0 30± 0 .0 0 2 )比 (0 .0 42± 0 .0 0 3) ,P <0 .0 5 ) ]。结论　phVEGF基因涂布支架可加速支架内皮化的形成 ,进而抑制血管内支架置入术后血栓形成和内膜增殖引起的再狭窄发生。     

巨细胞病毒感染与冠状动脉支架内新生内膜组织量的关系

目的　探讨巨细胞病毒 (CMV)感染对冠状动脉支架内内膜增生的影响。方法　 180例冠心病患者 ,于冠状动脉内支架置入术后 6个月复查冠状动脉造影和血管内超声检查。定量冠状动脉造影测定随访时的腔径减小 ,血管内超声测定支架内的平均新生内膜组织面积及其与支架横截面积之比。酶联免疫吸附法测定抗人CMVIgG抗体。 结果　CMV感染率达 5 1%。平均血管参考直径为 (2 94± 0 4 8)mm ,支架置入使平均最小腔内直径由 (0 99± 0 35 )mm上升至 (2 4 5± 0 4 2 )mm。 6个月随访时平均腔径减小 (0 74± 0 5 0 )mm ;平均新生内膜组织面积为 (3 8± 1 7)mm2 ,其与平均支架横截面积之比为 (4 5± 18) %。逐步多变量回归分析显示上述再狭窄指标与CMV感染无关联。结论　既往CMV感染与冠状动脉支架内新生内膜组织量无关。     

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。     

雌激素洗脱支架植入兔腹主动脉对内膜增生及内皮化的影响

目的评价雌激素洗脱支架对在体兔腹主动脉内膜增生及内皮化的影响。方法雄兔高脂喂养制成高脂血症模型后分三组,分别于腹主动脉植入裸金属支架、磷酸胆碱涂层支架和17β雌二醇洗脱支架,前两种支架作为对照。每组18只,各组于术后2、4及12周取出6只兔的支架段腹主动脉,测算支架处血管腔面积、新生内膜厚度和面积及管腔狭窄百分比以评价内膜增生程度。应用免疫组织化学染色法分析各时相支架段血管内膜Ⅷ因子阳性率以评估其再内皮化程度。结果3组不同支架植入后导致的血管损伤积分在各时相基本相同(2.17±0.22、2.18±0.21和2.17±0.19,P>0.05);各组支架植入2周时血管内膜已经增厚,在12周时管腔狭窄均<50%,但12周时雌二醇洗脱支架组新生内膜面积较裸金属支架组减少36%(P<0.01),磷酸胆碱涂层支架组与裸金属支架组相比无明显差别;2周与12周时新生内膜面积比在雌二醇洗脱支架组、磷酸胆碱涂层支架组、裸金属支架组分别为0.77、0.61和0.61(P<0.01)。2周时雌二醇洗脱支架组内皮化率明显高于裸金属支架组及磷酸胆碱涂层支架组(78.4%±2.3%比61.4%±3.4%及62.8%±2.9%,P<0.01),4周时各组血管内膜均接近完全内皮化。结论雌二醇洗脱支架可明显减少血管内支架植入后的内膜增生,加速支架段血管的再内皮化,具有良好的对抗再狭窄的应用前景。     

载Rapamycin多聚物涂层支架在猪冠状动脉模型预防再狭窄的实验研究

目的　评价载Rapamycin(RAP)新型可降解多聚物涂层支架在小型猪冠状动脉模型的可行性、安全性和预防再狭窄的疗效。方法　体外模拟测定从药物从膜释放的持续时间。支架多聚乳酸 /多聚羟基乙酸 (PLGA)涂层包埋RAP药物剂量为 4 0 0 μg(小剂量 )或 80 0 μg(大剂量 )。小型猪冠状动脉置入过大的裸支架、单PLGA涂层支架或含RAP涂层支架并形成冠状动脉损伤模型 ,术后第 5周重复定量冠状动脉造影术 (QCA)后处死动物 ,测定三组支架血管段的损伤积分、冠状动脉横断面积、管腔面积、内膜厚度和面积 ,并作比较。同时观察支架边缘段 5mm内血管组织。结果　药物从涂层膜释放时间达 30d。三组分别为裸支架组 (置入支架数n =5 ) ,单涂层组 (n =7)和RAP组 (n =8,其中小剂量为 3只 ,大剂量组为 5只 )。三组冠状动脉大小和血管损伤程度基本相同 ,裸支架组、单涂层组和RAP组的血管平均损伤积分分别为 1 84± 0 32 ,1 83± 0 35和 1 83± 0 2 6 (P =0 996 )。术后 5周 ,三组的管腔面积分别为 (6 7± 1 5 )mm2 ,(5 8± 4 0 )mm2 和 (9 7± 2 1)mm2 (P <0 0 5 ) ,RAP组最大。平均内膜厚度分别为 (0 5 1± 0 12 )mm ,(0 6 4± 0 46 )mm和 (0 2 0± 0 11)mm(P <0 0 5 ) ,RAP组最小。三组均未见支架边缘狭窄和     

冠状动脉内超声评价支架再狭窄

目的探讨冠状动脉内支架再狭窄的机制.方法50例确诊冠心病患者接受65个支架置入术,10个月后复查冠状动脉造影和血管内超声成像检查.根据冠状动脉造影结果将患者分为支架再狭窄组(26个支架)和无支架再狭窄组(39个支架),分别对其冠状动脉造影和血管内超声进行定量测量分析.同时观察支架内再狭窄的方式.结果血管内超声定量测量发现支架再狭窄组最小血管内膜腔面积和支架最小截面积[分别为(2.5±1.2)mm2和(4.2±1.8)mm2]明显小于无支架再狭窄组[分别为(5.2±1.4)mm2和(6.8±1.7)mm2](P分别＜0.001和＜0.01),但两组新生内膜截面积比较差异无显著性[分别为(1.7±1.0)mm2和(1.5±0.9)mm2,P＞O.05].支架内再狭窄以局灶性狭窄为多见(69.2%).结论支架扩张程度是决定支架内再狭窄的重要因素,而支架内内膜增生并不明显.支架内再狭窄以局灶性狭窄为多见.     

冠状动脉内置入国产支架的实验研究

目的　评价金新动脉支架置入小型猪正常冠状动脉内的可行性 ,观察支架置入后各时相支架段血管开通情况及血管内膜反应。方法　将 39枚国产冠状动脉内支架置入 2 0头小型猪冠状动脉内 ,每头小型猪的左前降支及左回旋支各被置入支架 1枚 ,观察置入 2 4h、1周、2周、4周、12周及 6个月血液动力学、肝功能、肾功能变化及冠状动脉造影随访结果 ,并对支架置入段血管进行光镜及电镜检查。结果　①该种冠状动脉内支架置入成功率为 97 5 % ,支架置入对血液动力学、肝功能、肾功能无影响。②冠状动脉造影随访示所有支架置入即刻和动物处死前支架段血管开通率10 0 %。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。未见与置入支架有关的心脏事件发生。③组织病理学形态分析显示新生内膜由不同排列的纤维组织和平滑肌细胞 (SMCs)组成 ,置入支架 1周开始有内膜覆盖支架丝 ,2周时可检测到光滑的新生内膜 ,置入支架后 1周、2周、4周、12周、2 4周支架小梁处新生内膜厚度分别为(5 6 17± 31 15 ) μm、(10 9 72± 4 1 6 1) μm、(348 2 5±5 6 78) μm、(2 5 6 2 5± 5 5 97) μm、(14 8 6 1± 39 82 ) μm。支架小梁间新生内膜厚度分别为 (37 2 1± 2 7 5 0 ) μm、(6 4 5 6±36 5 7) μm、(1     

Effectiveness of Biodegradable Magnesium Alloy Stents in Coronary Artery and Femoral Artery

Objectives

To access the biocompatibility, effectiveness, and safety of biodegradable magnesium (Mg) alloy stent (BMAS) in the coronary artery and femoral artery.

Background

Atherosclerosis is a lesion of cardiovascular system, including the diseases in heart and blood vessels.

Methods

The aluminum (Al) and zinc (Zn)‐based BMAS was designed by cold drawing methods. Forty healthy immunized mongrel dogs were randomly divided into 8 groups. Five dogs who have not been treated with stent were included in control group. The other dogs were implanted with an absorbable magnesium (Mg) alloy in the coronary and/or femoral artery, and their artery angiography were observed at 7 time points (1, 3, 5, 7, 14, 21, and 28 days; n = 5) follow‐up. Dogs from each cohort were sacrificed following angiography for pathology assessment. The histological response including inflammatory response, thrombosis, and intimal hyperplasia were analyzed by hematoxylin‐eosin staining. Lumen area (La), intimal hyperplasia area (IHa), and the ratio of IHa were calculated by image analysis software.

Results

The thin‐walled BMAS were designed and produced by cold‐drawing technology. Fifty‐one devices were implanted into coronary artery of 35 dogs successfully. During the follow‐up days, the angiography of coronary artery and femoral artery had confirmed that the lumen was clear and there were no elastic recoil and thrombosis. The stents were completely disappeared at 7 days after implantation. Moderate intimal hyperplasia was found at 14 days after implantation.

Conclusion

The BMAS stent proved to be of good biocompatibility, safety, and effectiveness. (J Interven Cardiol 2015;XXXX:XX–XX)

     

Safety and efficacy of bioabsorbable magnesium alloy stents in porcine coronary arteries.

OBJECTIVE: We aimed to determine the safety and efficacy of biobasorbable magnesium alloy stents in porcine coronary arteries. Bioabsorbable magnesium stents carry the potential to overcome the limitations posed by permanent metallic stents such as chronic inflammation, late stent thrombosis, prolonged antiplatelet therapy, and artifacts when imaged by multislice-computed tomography or magnetic resonance imaging. METHODS: Magnesium alloy stents or stainless steel stents were randomly deployed in coronary arteries of domestic or minipigs. Domestic pigs were sacrificed at 3 days (n = 2) or 28 days, and minipigs at 3 months. RESULTS: At 3 days, magnesium alloy stents were intact, but started to show signs of degradation by 28 days. There was no evidence of stent particle embolization, thrombosis, excess inflammation, or fibrin deposition. At 28 days and 3 months, neointimal area was significantly less in magnesium alloy stent segments (2.44 +/- 0.88 mm(2) and 1.16 +/- 0.19 mm(2)) as compared with the stainless steel stent segments (5.03 +/- 1.5 mm(2) and 1.72 +/- 0.68 mm(2), P < 0.001 and 0.02). Quantitative coronary analysis indicates that percentage area stenosis and percentage diameter stenosis in magnesium alloy stent segments improved significantly at 3 months as compared to 28 days. Despite decreased neointimal hyperplasia, lumen area of the magnesium alloy stented vessels did not improve significantly. CONCLUSION: Magnesium alloy stents are safe and are associated with less neointima formation; however, reduced neointima did not result in larger lumen.     

冠状动脉内置入国产支架的动物实验研究

目的　观察国产支架置入犬冠状动脉后的生物、血液相容性、支架开通率及其内皮化情况。方法　将16个国产支架置入8只犬的冠状动脉内,分别于1、2、3、6个月进行观察。结果　支架置入术后冠脉通畅,无明显狭窄。支架贴内膜良好,血管内腔表面光滑。术后2个月时支架覆盖的新生内膜最厚,其主要为平滑肌细胞和细胞外基质,未见明显炎性细胞浸润。支架置入1个月时,支架表面覆盖的内皮细胞排列不规则;置入2、3、6个月时,其沿血流方向排列规则。支架表面未见明显腐蚀。结论　该国产支架置入后有良好的生物和血液相容性,理化性能稳定,迅速重新内皮化,有良好的开通率。     

Short-term effects of biocorrodible iron stents in porcine coronary arteries

BACKGROUND: Biocorrodible iron stents carry the potential to overcome limitations, such as chronic inflammation and premature recoil, posed by biodegradable polymer and magnesium alloy stents. This study aimed to test the safety and efficacy of biocorrodible iron stents in porcine coronary arteries. METHODS: Iron stents and cobalt chromium stents were randomly deployed in the coronary arteries of juvenile domestic pigs. Animals were sacrificed at 28 days, and the vessels were fixed and processed for histochemistry. RESULTS: At 28 days, iron stents started to show signs of degradation without evidence of stent particle embolization or thrombosis without traces of excess inflammation, or fibrin deposition. At 28 days, the surface of the iron stent struts was black to brown and the vascular wall adjacent to the iron stent had a brownish tinge. There were no statistically significant differences in any of the measured parameters between segments implanted with iron and cobalt chromium stents. There were also no adverse effects in the persistent areas. CONCLUSION: The current study demonstrates that stents made of biocorrodible iron are safe. In some of the measured parameters, such as intimal thickness, intimal area, and percentage occlusion, there was a trend in favor of the iron stents.     

Low-energy gamma-emitting stents inhibit intimal hyperplasia with minimal "edge effects" in a pig coronary artery model.

PURPOSE: The objective of this study was to determine the effects of different doses of gamma-emitting radioactive stents on intimal hyperplasia in a porcine coronary stent model at 28 days. METHODS: Sixty-four bare stents and those coated with palladium-103 [activities of 0 (control), 0.5, 1.0, 2.0, and 4.0 mCi] were implanted in the coronary arteries of 32 pigs. Stented segments were evaluated by histomorphometry at 28 days. RESULTS: There was significantly more intima in the 0.5- and 1-mCi stents than in controls (4.27+/-0.52 and 4.71+/-1.13 vs. 1.71+/-0.61 mm(2); P<.0001). Neointimal formation in 2-mCi stents was similar to that in controls, while that in 4-mCi stents was reduced compared to that in controls (2.34+/-1.61 and 0.82+/-0.25 vs. 1.71+/-0.61 mm(2); P=NS and P<.05, respectively). Stent margin neointimal response was representative of that within the stent body, with nonsignficant modest increases in intimal area at adjacent nonstented segments in radioactive stent groups. There was a dose-dependent increase in inflammation scores. Radioactive stents had lower intimal smooth muscle and higher fibrin scores. There was an increase in adventitial fibrosis in 1- and 2-mCi stents versus controls (1.26+/-0.99, and 2.25+/-1.27 vs. 0.21+/-0.31; P<.001). CONCLUSION: Dose-response inhibition of in-stent hyperplasia with minimal "edge effects" occurs with low-energy gamma-emitting stents. An increased inflammatory response at higher doses in palladium-103 stents indicates that later follow-up studies are necessary.     

莪术组分涂层支架预防猪冠状动脉再狭窄的研究

目的通过中华实验用小型猪冠状动脉再狭窄模型,观察中药莪术组分涂层支架抑制内膜增殖的有效性。方法将18只小型猪随机分为莪术组分涂层支架组(ZES组)、雷帕霉素涂层支架组(SES组)及金属裸支架组(BMS组),每组6只,分别在左前降支、左回旋支及右冠状动脉置入同一种支架各1枚。术后30 d冠状动脉造影后将猪处死,观察支架血管段的病理形态及影像学变化。结果 30 d时,与BMS组比较,ZES组和SES组平均管腔直径和平均管腔面积均明显增大(P<0.05),直径狭窄率和面积狭窄率明显减小(P<0.05);与SES组比较,ZES组和BMS组炎症积分明显降低,内皮化积分明显升高(P<0.05);3组损伤积分比较,差异无统计学意义(P>0.05);光学相干断层扫描及扫描电镜观察,SES支架组30 d时可见部分支架节段内皮化不全及炎性细胞浸润。结论 ZES支架可有效地抑制血管内膜增殖,具有良好的生物相容性。     

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.     

Stents covered by an autologous arterial graft in porcine coronary arteries: feasibility, vascular injury and effect on neointimal hyperplasia.

OBJECTIVE: The use of stents has improved results after balloon coronary angioplasty. Several materials have been proposed for covering the metallic surface of the stent to reduce the rate of subacute thrombosis and restenosis. In our institution, an autologous arterial graft was used for covering the external surface of a conventional stent. The angiographic and histological response in a porcine coronary artery model was investigated. METHODS: An autologous arterial graft was removed from the femoral artery and carefully prepared. Subsequently, a conventional stent was covered externally by the arterial graft. Twenty-two covered stents and 22 uncovered regular stents were implanted alternatively in the coronary arteries of 22 pigs. One animal died immediately after the procedure, due to thrombus formation in the uncovered stent. Six animals were sacrificed at seven days and the remaining animals were sacrificed at two months. Before the sacrifice, coronary angiography was performed in all animals. RESULTS: Thrombosis was detected in two control segments and in one covered stented segment. After seven days, the luminal surface of the covered stents was covered by a new endothelial layer in contrast to partial endothelial cell appearance in the control group. The angiographic parameters were similar between the two groups. Histologically, the covered stents were associated with less vascular injury compared to uncovered stents. In covered stents a trend towards reduction of maximal intimal hyperplasia was detected (covered: 116.6 +/- 47.75 vs uncovered: 150.25 +/- 46.81 microns, p = 0.08); also the thickness of the arterial media was reduced (covered: 21.34 +/- 10.28 vs uncovered: 102.63 +/- 18.71 microns, p = 0.02). The luminal and vessel areas were similar in the two groups. CONCLUSIONS: The preparation and implantation of the autologous arterial graft-covered stent is technically safe and feasible. This type of covered stent results in accelerated endothelialization, less vascular injury, thinning of the arterial media and a trend to reduce the intimal hyperplasia in normal coronary arteries.     

Stent design related neointimal tissue proliferation in human coronary arteries; an intravascular ultrasound study.

AIMS: Histological restenosis models in animals have indicated that stent design has a significant impact on vessel trauma during stent implantation and on the amount of subsequent neointimal tissue proliferation. The impact of different stent designs on intimal hyperplasia in human atherosclerotic coronary arteries has not been determined. METHODS AND RESULTS: Angiographic and intravascular ultrasound studies were performed at the 6 month follow-up in 131 consecutive native coronary lesions of 131 patients treated with 50 Multi-Link stents, 40 InFlow stents and 41 Palmaz-Schatz stents. Lumen and stent cross-sectional areas (CSA) were measured at 1 mm axial increments. Mean intimal hyperplasia cross-sectional area (stent CSA-lumen CSA) and mean intimal hyperplasia thickness were calculated. Intravascular ultrasound demonstrated different levels of intimal hyperplasia proliferation for the three stents. Mean intimal hyperplasia thickness was 0.16+/-0.08 mm for Multi-Link stents, 0.26+/-0.19 mm for Palmaz-Schatz stents and 0.39+/-0.14 mm for Inflow stents (P<0.001). Multivariate analysis proved that stent type was the only independent predictor of intimal hyperplasia thickness at follow-up (P<0.001). CONCLUSION: Coronary stent design has a significant impact on subsequent intimal hyperplasia after implantation into atherosclerotic human coronary arteries. The corrugated ring design of the Multi-Link stent proved to result in less tissue proliferation at 6-month follow-up than the tubular slotted design of Palmaz-Schatz and InFlow stents.     

大蒜素包膜支架对犬冠状动脉损伤后再狭窄的影响

目的 :评价一种新型包膜支架携带和释放大蒜素的能力 ,并观察大蒜素包膜支架对术后再狭窄的影响。方法 :选取 6只犬 ,将大蒜素包膜支架和对照支架分别置入左回旋支的远端 (大蒜素支架组 ,n =6)和近端 (对照组 ,n =6) ,于支架置入术后 1个月行冠状动脉造影后处死 ,光镜下观察内膜增生情况。另选取 10只犬 ,分别于大蒜素包膜支架置入后 1h、1d、3d、10d和 2 8d处死 ,用高效液相色谱法测血管局部的大蒜素浓度。结果 :大蒜素包膜支架置入体内 1h、1d、3d、10d、2 8d时的血管壁浓度分别为 80 83、67 5 0、11 79、0 3 3、0 2 6ng/mg组织。术后 1个月 ,大蒜素支架组和对照组血管的损伤程度相同 ,大蒜素支架组的血管内膜增生和再狭窄程度明显低于对照组。结论 :血浆包膜支架可有效携带和释放药物 ,大蒜素包膜支架可抑制术后再狭窄发生。