基质金属蛋白酶与支架内再狭窄研究进展

近年来,随着冠心病发病率逐渐升高,经皮冠状动脉介入治疗(PCI)已成为重要的治疗手段。但是PCI术后并发的支架内再狭窄(in-stent restenosis,ISR)使该技术受到一定的限制。在金属裸支架(BMS)时代,再狭窄率高达17%～32%。在药物洗脱支架(DES)时代,再狭窄率依然达10%左右[1]。ISR已成为PCI技术继续发展的难题。随着人们对ISR机制研究的不断深入,     

准分子激光冠状动脉斑块消融术治疗冠状动脉支架内重度狭窄伴消化道出血一例

正经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)是目前治疗冠状动脉粥样硬化性心脏病的主要手段之一,但PCI术后可能发生的支架内再狭窄(in-stent restenosis,ISR)仍然困扰着临床医生。虽然药物洗脱支架的问世极大地降低了ISR的发生率,但据统计再狭窄率仍高达5%~20%~([1-3])。目前ISR常用的处理方法包括支架内支架     

冠状动脉慢性完全闭塞病变经皮介入治疗术后支架内再狭窄的影响因素分析

目的:探讨冠状动脉慢性完全闭塞病变(chronic total occlusion,CTO)经皮介入治疗(percutaneous coronary interven-tion,PCI)术后发生支架内再狭窄(in-stent restenosis,ISR)的影响因素。方法:分析2004年1月—2009年12月接受冠状动脉造影(coronary angiography,CAG)并成功植入药物支架的129例CTO患者的临床资料。根据CAG随访是否出现再狭窄,将129例患者分为再狭窄组和非再狭窄组。采用单因素及Logistic多因素分析影响CTO病变PCI术后发生ISR的因素。结果:129例患者中,发生ISR者24例(18.6%)。与非再狭窄组比较,再狭窄组有既往心肌梗死病史患者比例较高(54.2%比31.4%,P=0.036),即时最小管腔直径(minimal lumen diameter,MLD)较小[(2.13±0.31)mm比(2.29±0.40)mm,P=0.038)]。Logistic多元回归分析显示,既往心肌梗死史(P=0.045,OR=3.268)、术后即时MLD(P=0.049,OR=0.071)为CTO病变植入药物洗脱支架后发生再狭窄的独立负性预测因素。结论:既往心肌梗死病史、术后即时MLD与CTO病变植入药物洗脱支架后发生再狭窄相关。     

药物洗脱支架:较强安全性和良好近远期效果之评价

目的:评价冠状动脉介入治疗中应用药物支架置入后的效果、安全性.方法:以"经皮冠状动脉成形术,药物血管支架,内膜增生,再狭窄,生物相容性"为关键词,采用计算机检索2000-01/2009-12相关文章.纳入与血管支架材料,血管支架材料改性相关的文章,排除重复研究或Mata分析类文章,以14篇为重点,讨论载药支架对血管内皮增生、再狭窄及生物相容性的影响.结果:药物支架具有在血管病变部位将药物自聚合物涂层中通过洗脱方式有控制的释放至心血管壁组织而发挥生物学效应的特点.以雷帕霉素洗脱支架为代表的药物支架在冠状动脉粥样硬化性心脏病(冠心病)的介入治疗中,有效降低了支架内再狭窄和心血管事件的发生率,对糖尿病患者、小血管病变、冠状动脉长病变和弥漫性复杂病变治疗方面也显示出良好的疗效.文献还显示国产雷帕霉素洗脱支架与进口雷帕霉素洗脱支架相比同样具有良好的安全性,但由于支架携带的药物本身和承载药物的涂层作用,是否会引起晚期支架内血栓引起了临床的重视,科研人员也在通过对支架晚期支架内血栓机制、可控血栓危险因素的干预策略和支架工艺技术的研究,积极探索新一代的既减少支架再狭窄又减少支架血栓更安全的药物洗脱支架.结论:以雷帕霉素洗脱支架为代表的药物支架在多种冠心病的介入治疗中,能有效降低支架置入后血管内再狭窄和心血管事件的发生率,有较强的安全性和良好的近远期疗效.     

药物洗脱球囊在冠状动脉支架术后再狭窄治疗中的应用效果

目的分析药物洗脱球囊(DEB)用于冠状动脉支架术后再狭窄治疗中的效果。方法选取济源市第二人民医院2017年6月至2018年6月收治的40例冠状动脉支架术后再狭窄患者为研究对象,随机分为对照组与研究组,每组20例。对照组给予紫杉醇药物洗脱支架治疗,研究组给予药物洗脱球囊(DEB)治疗。比较分析研究组与对照组患者术后心血管不良事件发生情况、管腔狭窄率及最小管腔长径等临床指标。结果术后12个月,研究组与对照组最小管腔长径分别为(2.60±0.43)mm与(2.57±0.42)mm,差异未见统计学意义(P>0.05)。两组患者术后心血管事件发生率、管腔狭窄率及冠状动脉支架术后再狭窄率比较,差异未见统计学意义(P>0.05)。结论DEB用于冠状动脉支架术后再狭窄治疗中的效果理想,安全性高,与药物洗脱支架治疗相比疗效并无显著差异,具有临床推广意义。     

金属裸支架与国产药物洗脱支架置入冠状动脉长病变后的血管重建及生物相容性效应

目的:对比国产雷帕霉素药物洗脱支架(firebird火鸟)和金属裸支架置入冠状动脉长病变血管后的安全性、生物相容性及血管重建作用.方法:选取2005-07/2007-07抚顺矿务局总医院行支架置入治疗冠状动脉长病变(单根血管病变长度≥20mm)患者215例为观察对象.置入药物洗脱支架134例,置入金属裸支架81例.支架均由微刨医疗器械(上海)有限公司提供.置入者为本科从事冠状动脉介入治疗≥10年的副丰任医师.根据病变血管近端及远端血管直径,按1:1比例选择支架,支架长度以超过病变两端3～5 mm为准,置入术中经动脉鞘管注入肝素5 000 U,术后腹壁皮下注射低分子肝素钙0.4 mg共3 d,大部分患者使用球囊进行预扩张.冠状动脉造影定量分析支架内或支架临近血管(5 mm)管腔直径狭窄程度＞50%为血管造影再狭窄.结果:共215例患者238处靶病变完成冠状动脉造影检查随访.①术后1个月复查血常规,凝血相检查,无一例出现造血系统细胞成份、数目、形态不良改变.②随访造影显示无一例支架松脱、移位;无一例血管局部增生反应.③对影响长病变支架再狭窄因素的logistic回归分析发现,支架类型是对长病变支架内再狭窄影响最大的危险因素.④置入后6个月随访置入药物洗脱支架组再狭窄率为15.49%,置入金属裸支架组再狭窄率为47.92%,两组比较差异有显著性意义(P＜0.001),药物洗脱支架组靶病变血管重建率、置入支架后扩张的比例要明显好于金属裸支架组(P＜0.001).结论:国产雷帕霉素药物洗脱支架(firebird火鸟)在置入冠状动脉长病变后无特殊生物相容性反应,在降低再狭窄率及血管重建方面优于金属裸支架.     

血管内支架表面生物涂层材料与血管内再狭窄

背景:心脏病是威胁人类健康的首要病因之一,现在全世界每年大约有1 500万例冠心病患者需要接受经皮穿刺冠状动脉(冠脉)成形治疗,但是大约10%发生急性或亚急性冠脉阻塞,6个月后再狭窄发生率高达20%~50%,再狭窄已成为制约经皮穿刺冠状动脉(冠脉)成形术发展的最主要因素.目的:探讨药物洗脱支架治疗支架内再狭窄的长期临床效果.方法:作者以"药物洗脱支架,阻塞,再狭窄"为检索词,在中国期刊全文数据库中,采用电子检索的方式进行文献检索.排除Meta分析及重复性研究,共检索到25篇文献,从支架置入治疗进展,不同材料及类型支架对开通率、开通时间的影响,以及预防支架狭窄等方面进行探讨.结果与结论:药物洗脱支架运用先进的支架载药及药物控制释放技术,在支架机械支撑病变血管的同时,具有抑制血管平滑肌细胞增生的药物从支架表面缓慢释放,作用于与支架接触的血管壁,解决了血管弹性回缩、重塑以及内膜的过度增生问题.随着冠状动脉介入治疗设备的改进和创新,药物涂层支架技术也在不断地成熟和发展.目前新出现的药物涂层支架设计理念是建立在药物筛选和可控释放系统基础上的.相信未来的药物涂层支架将能够应用于更多的血管复杂病变(尤其是静脉和多血管损伤)以及其他脏器疾病.     

国产微创冠状动脉药物洗脱支架的临床疗效

冠状动脉介入治疗已广泛用于冠心病的治疗,支架的应用明显降低了经皮冠状动脉腔内成形术（PTCA）引起的急性闭塞及再狭窄率.但支架同样面临再狭窄的问题,尤其是复杂病变及合并有糖尿病患者的病变血管,更易发生再狭窄.药物涂层支架可明显降低再狭窄的发生,这在国内外的一些文献中均有报道,且已在临床广为应用.我国当前在介入治疗中使用的药物洗脱支架多依赖进口技术,国产药物洗脱支架（Fire Bird、微创医疗器械一上海有限公司）在临床使用时间短,目前尚无关于其临床疗效的报道.我们对20例患者成功使用国产药物洗脱支架,并观察其临床疗效及安全性.     

改良Y型支架植入术治疗冠状动脉分叉病变的安全性和有效性探讨

药物洗脱支架在临床的广泛应用,显著降低了经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)术后的再狭窄率[1].介入治疗成为冠心病治疗的重要手段,但冠状动脉分叉病变的介入治疗始终是冠心病介入治疗的难题,随着介入技术的不断进步,冠状动脉分叉病变分支支架植入的即刻成功率也明显提高[2],但分支血管开口的再狭窄率仍然较高,考虑主要原因为分支开口未得到支架及药物的完全覆盖[3].经典的Crush技术能够保证有效的覆盖分支开口,但是由于最终球囊对吻成功率低,故支架内再狭窄及支架内血栓事件发生率仍较高[4],改良的Y型支架植入技术能够保证分支开口得到有效的覆盖,降低了分支支架内再狭窄率,本研究旨在通过与经典Crush技术比较来评价改良Y型支架植入技术的安全性及有效性.     

平滑肌细胞周期基因调控的研究进展

支架后再狭窄(in-stent restencois,ISR),被认为是腔内血管重建期间动脉损伤后的一种自我修复反应,其发生率高达5%～30%[1],已成为目前支架临床应用的主要受限因素.近年来,随着心脑血管疾病发病率的逐年增高,支架介入治疗因其强大的优势已成为治疗的首选方法之一,但ISR的发生束缚了其临床应用.为解决这一棘手问题,全球针对ISR展开了深入研究,各种药物洗脱支架相继应用于临床,但ISR的发生率仍未控制到满意水平.     

Local drug delivery for percutaneous coronary intervention

Since the first successful coronary angioplasty by Andreas Grüntzig in 1977, the field of percutaneous coronary intervention (PCI) has expanded rapidly. Rapid technological refinement has seen equipment and complementary pharmacotherapy to improve the outcome of PCI evolve dramatically, driven by clinical need and enormous market forces. The ideal intervention should expand the vessel lumen without inflicting endothelial injury, and provide local drug delivery to prevent subsequent acute thrombosis and neointimal hyperplasia. Drug eluting stents, once regarded as the "gold standard" in PCI, and established as the treatment of choice for nearly a decade, remain limited in their performance by important risks of in-stent restenosis and late stent thrombosis. In this review, we discuss need for local drug therapy as an adjunct to angioplasty and present exciting new technological advances to deliver local pharmacotherapy to the coronary artery, which will hopefully overcome some of the limitations of DES and may represent the way forward in coronary intervention.     

Prevention of coronary in-stent restenosis and vein graft failure: Does vascular gene therapy have a role?

Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI), including stent insertion, are established therapies in both acute coronary syndromes (ACS) and symptomatic chronic coronary artery disease refractory to pharmacological therapy. These continually advancing treatments remain limited by failure of conduit grafts in CABG and by restenosis or thrombosis of stented vessel segments in PCI caused by neointimal hyperplasia, impaired endothelialisation and accelerated atherosclerosis. While pharmacological and technological advancements have improved patient outcomes following both procedures, when grafts or stents fail these result in significant health burdens. In this review we discuss the pathophysiology of vein graft disease and in-stent restenosis, gene therapy vector development and design, and translation from pre-clinical animal models through human clinical trials. We identify the key issues that are currently preventing vascular gene therapy from interfacing with clinical use and introduce the areas of research attempting to overcome these.     

Overview of therapies for prevention of restenosis after coronary interventions

Coronary artery disease is a leading cause of morbidity and mortality in the United States and across the world. The economic impact of coronary artery disease is staggering and on the rise. Percutaneous transluminal coronary angioplasty is widely used to treat severe, symptomatic coronary stenosis. The Achilles heel of angioplasty is restenosis of those treated arteries. As a result, numerous therapies, including mechanical and pharmacological approaches, to prevent restenosis have been studied. A greater understanding of the pathophysiology of restenosis has enhanced the success of these therapeutic approaches. To date, the most important and successful approach to limit restenosis has been the use of coronary stents. Stents have reduced the rate of restenosis from approximately 50% down to 20-30%. However, in-stent restenosis presents a new and an even more challenging dilemma. The success of adjunctive drug therapy has been promising, but, as of yet, very limited. Antithrombotic agents have reduced acute thrombosis and many of the acute complications of angioplasty. New approaches and therapies are very encouraging, and provide great hope in the treatment of restenosis. Brachytherapy has shown success in the treatment of in-stent restenosis, and recently has been approved by the United States Food and Drug Administration for this indication. Drug-eluting stents using antiproliferative drugs are the most exciting new advance in preventing restenosis, currently in Phase III trials. Gene therapy, targeted drug delivery, and newer antithrombotic agents are also under investigation. We will review the pathophysiology of restenosis, animal models, pharmacological therapies, and mechanical approaches for the treatment of restenosis.     

冠脉支架术后患者支架内再狭窄原因的回顾性研究

目的 通过对冠脉支架植入术后复查冠脉造影患者的回顾性分析,研究引起支架内再狭窄(ISR)的可能原因.方法 入选2009年～2010年所有复查造影的冠心病支架治疗患者73例,将其分成支架内再狭窄组及无再狭窄组,分析两组间可能导致支架内再狭窄的因素间差异.结果 73例患者共植入177枚支架,其中有22枚支架发生再狭窄(支架内再狭窄定义为随访时造影提示支架内管腔内径损失≥50%).分析两组基本临床资料特征及支架长度、直径,是否为药物涂层支架等因素;支架内再狭窄组及无再狭窄组在吸烟、2型糖尿病、支架长度、直径和药物/非药物支架方面有显著差异(P ＜0.05).Cox比例风险回归模型显示仅支架长度(P=0.009)、直径(P=0.029)和药物/非药物支架(P=0.026)为冠心病介入患者发生ISR的预测因子.结论 冠脉支架植入后发生再狭窄的主要原因为支架长度、直径及是否为药物支架.     

急性冠脉综合征血管内超声检查的效益分析

目的评价血管内超声检查(IVUS)在急性冠脉综合征(ACS)患者中应用的意义和效益,为护理人员进行健康教育和医生动员病人接受检查提供量化依据。方法将50例ACS患者根据病人经济承受能力和意愿分为IVUS组及对照组,IVUS组(22例)患者行常规冠脉造影(CAG),IVUS指导经皮冠状动脉内介入治疗(PCI);对照组(28例)行常规CAG后直接行PCI。两组患者术后6个月复查。比较两组患者支架内再狭窄率及术后6个月内因心血管事件再住院率和医疗费用。结果术后6个月复查,IVUS组再狭窄率2.1%,对照组为35.3%,P<0.001;术后6个月内因心血管事件再住院率,IVUS组为9.1%,对照组为46.4%,P<0.01;两组患者医疗费用比较,IVUS组明显低于对照组,P<0.001。结论IVUS可准确判断血管狭窄程度指导支架置入达最佳状态,可降低冠脉再狭窄率和患者因心血管事件再住院率,在降低患者痛苦的同时明显降低患者承担的经济费用。     

基因学干预研究:血红素氧合酶1微卫星多态性表达水平上调的作用

背景人类血红素氧合酶1(Heme Oxygenase-1,HO-1)基因启动子区域有一双核苷酸(GT)n重复序列,有高度多态性,又称为微卫星多态性,体外实验表明通过测定GT重复次数可间接了解人体内HO-1的表达水平.目的探讨HO-1基因启动子双核苷酸GT n重复序列的微卫星多态性与冠状动脉支架术后再狭窄的关系.设计以接受冠状动脉支架置入术的冠心病患者为研究对象的病例对照研究.单位一所大学医院的心内科病房.对象研究对象为1996-04/2002-05北京大学第一医院心内科病房成功接受冠状动脉支架置入术的冠心病患者,共118例.纳入标准支架术后3个月以上行冠状动脉造影随访的冠心病患者;排除标准冠状动脉造影显示原靶病变管腔直径狭窄＜50%和冠状动脉造影随访时间＜3个月的冠心病患者.入选患者年龄(62±10)岁,男92例,女26例,所有患者均签署知情同意书.根据美国心肺血液协会的标准定义,将患者分为支架内再狭窄组与无再狭窄组,分别为68例和50例.方法提取患者外周血DNA,经PCR扩增HO-1微卫星序列后采用Spreadex凝胶电泳来进行基因分型.主要观察指标HO-1基因启动子微卫星基因型频率及其与再狭窄的关系. 结果携带GT重复＜25次等位基因患者的再狭窄率为47.5%,携带两条GT重复均≥25次等位基因患者的再狭窄率为68.4%(P＜0.05).经多元回归分析校正冠心病危险因素及介入治疗的相关影响因素后,两组患者的再狭窄率差异仍有显著性意义(OR=0.418,95%可信区间0.197～0.887,P＜0.05).结论HO-1基因启动子微卫星多态性与再狭窄相关,对冠心病患者冠状动脉支架置入术后的二级预防有十分重要的意义.     

双源CT冠状动脉成像对冠状动脉支架内再狭窄的评价

背景：化统的CT在冠心病介入治疗后随访中难以普及,寻找无创、有效的检查方法对支架内再狭带的评价就成了影像科医生非常关心的课题。目的：通过在不控制心率下双源CT冠状功脉成像与选择性冠状动脉造影对支架评估的对比,探讨双源CT冠状动脉成像对冠状动脉支架内再狭窄的诊断价值。方法：收集53例患者共75枚支架在不控制心率情况下同期行双源CT冠状动脉成像及冠状动脉造影检查的患者影像资料,分析双源CT冠状动脉成像诊断支架内再狭窄的敏感性等各项指标。     

经皮冠状动脉介入术后支架再狭窄因素临床评价

目的:分析冠心病患者经皮冠状动脉介入术后支架内再狭窄的影响因素,并探讨其规律。方法:回顾性分析本院行冠状动脉介入治疗术后再次行冠状动脉造影的167例患者临床资料,分析急性心肌梗死组和非心肌梗死组、有症状组和无症状组冠状动脉支架再狭窄的发生率。结果:急性心肌梗死组患者支架术后支架再狭窄率高于非心肌梗死组患者(P<0.05);合并糖尿病患者再狭窄率高于未合并糖尿病患者(P<0.05);术后有可疑心绞痛症状者支架内再狭窄率高于无症状定期随访者(P<0.05)。结论:(1)急性心肌梗死、糖尿病可能由于其本身的病变特征,易致冠状动脉介入治疗术后支架内再狭窄。(2)根据临床症状可以初步诊断支架内再狭窄。     

Is there a link between nickel allergy and coronary stent restenosis?

Although many patients with coronary artery disease are being treated by coronary stents, in-stent restenosis is the major limitation of percutaneous coronary stenting procedures. Most stents are made of stainless steel, and that, allergic reactions to nickel ions released from coronary stainless-steel stents may be one of the triggering mechanisms for in-stent restenosis. We aimed to evaluate the relationship between in-stent restenosis and nickel allergy in a prospective study. For this purpose, we applied epicutaneous patch test for nickel in 43 patients who had undergone elective intracoronary stent placement for stable angina pectoris in the day following stent placement and evaluated the presence of nickel allergy. Control angiography was performed at 6 months to determine in-stent restenosis. Three (6.9%) patients had allergic reaction to nickel and 16 (37%) patients had developed in-stent restenosis. One of the 3 patients with nickel allergy had diffuse in-stent restenosis and the others not. The present study therefore does not support the proposed relationship between nickel allergy and development of in-stent restenosis in patients having stainless steel stents. Large scale studies are needed to reach a final conclusion.     

Restenosis related to percutaneous coronary intervention has been solved?

Percutaneous coronary intervention (PCI) has become the most important revascularization method in the treatment of coronary artery disease. The major problem in PCI has been renarrowing of the dilated vessel after the procedure (restenosis). The best results in the prevention of restenosis have been obtained by covering the stent with drugs that inhibit cellular growth, thus limiting excessive scar formation inside of the stent. With drug-eluting stents, restenosis has been reduced to one-tenth compared with balloon angioplasty and to one-fourth compared to bare metal stents. Due to drug-eluting stents, PCI is an alternative to bypass surgery. However, restenosis will remain a challenge due to the increased number of procedures and more difficult disease treated with PCI.