内皮祖细胞与冠状动脉支架置入术后再内皮化的研究进展

冠状动脉内支架置入术已成为目前冠状动脉粥样硬化治疗的最重要手段之一,支架内涂层药物能抑制平滑肌细胞的生长,降低血栓发生率,但也抑制了内皮细胞的爬行,延迟了再内皮化的进展.如何促进再内皮化已成为关注的焦点,内皮祖细胞的发现和不断的研究进展,为再内皮化打开了一条新道路.     

药物洗脱支架载药涂层研究进展

药物洗脱支架自2002年在欧洲面世以来极大地改变了心血管介入术,与裸支架单一的机械支撑作用相比,药物洗脱支架在病灶处释放的药物能显著地降低再狭窄率。支架表面涂层作为一种重要药物靶向输送载体,能够最大程度地降低药物对系统的毒副作用,同时在药物的控制释放方面发挥重要的调节作用。涂层材料和制备技术不仅影响支架表面的生物相容性和支架植入过程的表面完整性,也决定了药物的输送传递方式和释放速率。本文介绍了血管载药支架作为临床治疗器械类产品的结构、技术、应用现状及具体面临的问题,在此基础上,分析提炼了相关涂层设计原则,阐述了近年来涂层材料和覆膜技术的研究进展,并展望了该领域的发展前景。     

血流储备分数（ffr）在冠心病介入治疗中的应用

目的：分析血流储备分数（ffr）在冠状病介入治疗中的应用价值,供临床参考。方法以本院收治的36例冠心病患者作为研究对象,随机分为对照组、观察组18例,对照组行冠脉介入治疗,植入药物涂层支架;观察组行血流储备分数测定,于数值≤0.80的病变处植入药物涂层支架。对比组间手术时间、造影剂使用量及植入支架累计数;出院1个月后,对比心绞痛症状及心脏不良反应情况。结果观察组造影剂使用量及植入支架累计数均少于对照组;组间手术时间、心脏不良反应发生率、心绞痛患者比例差异均无统计学意义（P〉0.05）。结论血流储备分数（ffr）有效指导冠脉介入手术,可减少造影剂临床使用量及植入支架累计量,并评价患者植入支架的贴壁效果。     

Cypher支架治疗完全闭塞病变的应用体会

完全闭塞病变是目前心脏介入领域的难点，据统计PTCA术后的再狭窄高达60％。药物涂层支架的出现是介入心脏病学继球囊成形术和支架植入术后的第三次革命。已证明Cypher支架在A，B型病变的治疗中，再狭窄几乎为零。我料自2003年1月至今共对12例完全闭塞病变行Cypher支架植入，现报告如下。     

不同冠心病患者药物涂层支架置入术后双抗血小板疗程的Meta分析

目的：系统评价不同冠心病患者药物涂层支架置入术后双抗血小板疗程的有效性和安全性。方法：检索MEDLINE、EMBASE和Cochrane Library数据库,获得冠心病患者药物涂层支架置入术后不同疗程双抗血小板治疗的随机对照试验,采用RevMan 5.2软件分别对性别、年龄、冠心病类型、是否合并糖尿病及置入不同药物涂层支架患者短疗程相对长疗程双抗血小板治疗的有效性和安全性进行Meta分析。结果：共检索到文献4 322篇,最终纳入9个随机对照试验,共30 244例患者。Meta分析显示非老年患者[RR 1.42,95%CI（1.20~1.70）]、置入紫杉醇[RR 1.70,95%CI（1.26~2.29）]和西罗莫司药物涂层支架[RR 1.71,95%CI（1.07~2.74）]的患者短疗程相对长疗程可增加未合并出血的主要复合终点发生率,而不同性别、老年患者、冠心病类型、是否合并糖尿病及置入依维莫司和佐他莫司药物涂层支架的患者短疗程相对长疗程双抗血小板治疗的主要复合终点发生率无显著性差异。结论：临床在为冠心病患者制定药物涂层支架置入术后双抗血小板疗程时应结合患者个体情况进行综合评估,对于非老年患者、置入紫杉醇和西罗莫司药物涂层支架的患者可在指南推荐的基础上适当延长双抗血小板疗程。     

药物涂层球囊在复杂冠脉病变中的应用进展

冠心病是我国常见疾病,心血管死亡已是我国居民首位死亡原因。冠脉支架植入是治疗冠心病的主要手段,但支架植入会带来支架内血栓、支架内再狭窄等问题。药物涂层球囊是近年新出现的介入器械,在支架内再狭窄和小血管病变中已得到广泛应用。随着研究进展,发现药物涂层球囊在复杂冠脉病变中也有一定的应用价值。本文就药物涂层球囊在冠脉分叉病变、急性心梗病变、冠脉弥漫病变及慢性闭塞病变中的应用做简要综述。     

国产药物涂层支架植入治疗168例冠状动脉闭塞病变疗效分析

目的分析国产药物涂层支架植入治疗冠状动脉闭塞（OCA）病变疗效。方法选择168例冠心病自发或诱发心肌缺血、IRA闭塞远端已有侧支循环形成病例,行国产药物涂层支架（吉威医疗制品有限公司和北京乐普医疗器械有限公司生产）植入治疗。根据治疗结果分为OCA开通组（A组）及未开通组（B组）,比较治疗前后及随访期间（6～18个月）各种疗效指标。结果手术成功率95．4％,OCA开通率89．7％。A组术后前向血流明显优于术前及B组同期结果（P〈0．05—0．01）;随访资料比较中,A组的心绞痛分级和心脏主要不良事件发生率明显低于B组,而左室射血分数和无缺血症状生存率则明显高于B组（P〈0．05～0．01）。结论国产药物涂层支架植入治疗OCA塞病变疗效较好。     

心脏支架材料的比较应用研究

心脏支架冠状动脉植入术是治疗冠心病的重要方法之一。随着生物材料技术的进步,心脏支架材料的应用取得了快速发展。本文介绍了心脏支架从金属支架到药物洗脱支架再到可溶性支架的变化过程,阐述了新材料支架的应用是降低心血管再狭窄率的重要途径,并对支架材料的未来给予了展望。     

雷帕霉素药物涂层支架治疗冠心病疗效评价

目的评价雷帕霉素药物涂层支架(CYPHER,Cordis)对冠心病的早期治疗效果。方法2002年12月至2004年10月38例冠心病患者置入CYPHER支架(38枚,药物支架组),随机选择同期38例接受普通、非药物涂层支架治疗(40枚,裸支架组),比较两组支架置入情况及早期临床事件发生率。结果两组间临床资料、冠脉病变的程度和分型差异无统计学意义,两组支架平均长度相似,但药物支架组平均支架直径较裸支架组显著减少。两组手术成功率相似(100%∶99·0%,P>0·05)。平均随访(5·0±3·1)个月,随访率98·7%,药物支架组心绞痛复发率显著低于裸支架组(5·2%∶23·7%,P<0·01)。结论冠心病患者应用雷帕霉素药物涂层支架治疗早期临床效果优于普通标准支架。     

冠心病患者冠脉支架植入术前后白细胞介素18水平变化

<正>冠脉支架植入术治疗冠心病、冠脉狭窄被广泛应用于临床。为探讨冠脉支架植入对炎性细胞因子的影响,明确金属裸支架的再狭窄和药物涂层支架的血栓再形成是否与炎性细胞因子有关,笔者测定了冠心病患者冠脉支架植入术前后     

Do the benefits of new technology outweigh the costs?

Over the past decade, coronary stenting has been shown to reduce the rates of angiographic and clinical restenosis compared with conventional balloon angioplasty; however, the use of bare-metal stents remains limited by a high incidence of restenosis, leading to frequent repeat revascularization procedures and substantial economic burden. Antiproliferative drug-eluting stents have recently demonstrated dramatic reductions in in-stent restenosis compared with conventional bare-metal stenting; however, the high cost of drug-eluting stents has raised important questions about the clinical and economic benefits of this ‘disruptive technology’. Prospective economic evaluations conducted alongside two randomized clinical trials (SIRolImUS-eluting stent in de novo coronary lesions [SIRIUS] trial and the RAndomized study with the sirolimus-eluting VElocity? balloon-expandable stent in the treatment of patients with de novo native coronary artery Lesions [RAVEL]) comparing drug-eluting stents with conventional bare-metal stenting, as well as decision-analytic models, have examined the economic merit of using drug-eluting stents. Findings from these studies suggest that although the initial treatment costs with drug-eluting stents are substantially higher, much of the difference in initial costs could be offset by reductions in follow-up costs, mainly due to a reduced requirement for repeat revascularization procedures. Results from these studies show that the cost effectiveness of drug-eluting stents varies considerably with the underlying clinical and angiographic characteristics of the patient population. While drug-eluting stents should be reasonably cost effective for most patients who currently undergo percutaneous coronary intervention (and cost saving for a sizeable minority), for certain subgroups with very low expected clinical restenosis rates (e.g. 5–10%), the routine use of drug-eluting stents may be questioned, at least on economic grounds. In the future, lower incremental costs for drug-eluting stents should render this technology cost saving for a larger subgroup of patients with PCI, and broaden the ideal target population.     

Recently patented applications of homologous cellular and extracellular agents as therapeutics or targets for the prevention of restenosis post-angioplasty

Currently available drug-eluting stents have been shown to reduce the prevalence of in-stent restenosis. However, their use is limited by their enormous cost and unwanted side effects associated with both drugs, sirolimus and paclitaxel, presently used to coat most of the stents clinically available. Due to their lack of selectivity with respect to targeted cell types these drugs do not only inhibit vascular smooth muscle cell proliferation underlying neointima formation, they also compromise endothelial repair increasing the risk for subacute thrombosis following implantation of drug-eluting stents. Accordingly, there is need for new cost-effective agents capable to inhibit restenosis without clinically relevant, unwanted side effects. In the present paper a selection of the most important patent applications published within the last 3 years and claiming the use of homologous cellular and extracellular agents as therapeutics or targets to prevent restenosis are reviewed. Such agents include c-Jun, the focal adhesion kinase (FAK) and its inhibitor FAK-related non-kinase (FRNK), estrogen receptors, variants of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) as well as some so far poorly characterized factors supposedly involved in the control of cell proliferation, inflammation and apoptosis. Such agents promise to be cost-effective and, in some cases, potentially devoid of unwanted side effects. Clinical long-term studies have yet to support such notions.     

Healing arterial ulcers: Endothelial lining regeneration upon vascular denudation injury

Thrombosis and restenosis are the most prevalent late complications of coronary artery stenting. Current standards of clinical care focus on prevention of smooth muscle cell proliferation by the use of drug-eluting stents able to release anti-proliferative drugs. Unfortunately, these drugs also block endothelial cell proliferation and, in this manner, prevent recovery of endothelial cell coverage. Continued lack of endothelial repair leaves the root cause of thrombosis and restenosis unchanged, creating a vicious cycle where drug-mediated prevention of restenosis simultaneously implies promotion of thrombosis. In this issue of Vascular Pharmacology, Hussner and colleagues provide in vitro evidence and a mechanistic basis for the use of atorvastatin in stents as a way to bypass this roadblock. Here we review the pathological mechanisms and therapeutic approaches to restore flow in occluded arteries. We argue that rational design of drug eluting stents should focus on specific inhibition of smooth muscle cell proliferation with concurrent stimulation of endothelial regeneration. We comment on the current poor understanding of the cellular and molecular regulation of endothelial cell proliferation in the context of a functional artery, and on the pitfalls of extrapolating from the well-studied process of neovascularization by sprouting vessel formation.     

Drug delivery systems for stents

Drug-eluting stents have emerged as the single most promising therapeutic approach to prevent restenosis, a formidable limitation of percutaneous coronary revascularization. Stent-based drug delivery engenders a number of critical chemical, drug, polymer, and mechanical engineering challenges that must be addressed to develop an effective restenosis therapy. The challenges of stent-based delivery using potent antiproliferative compounds and polymeric surface coatings are easily apparent in the design and development of first-generation drug-eluting stents. Adverse clinical outcomes with potent cytotoxic stent-based therapies, such as dactinomycin and a high dose, slow release paclitaxel derivative, represents the dark-side of the drug-eluting stent, with early aggressive patterns of restenosis, increased stent thrombosis, and aneurysm formation. These adverse clinical outcomes with drug-eluting stents highlight the importance of understanding the interactions of the drug and polymer, as well as the role of the residual polymer coating in determining long-term clinical results. The ultimate fate, or the ‘healed arterial response’ to residual polymeric material, remains a controversial issue due to the limited availability of long-term clinical follow-up data for most drug-eluting stents.     

The implications of human stem cell differentiation to endothelial cell via fluid shear stress in cardiovascular regenerative medicine: a review

Stem cell therapy heralds a new chapter in cardiovascular regenerative medicine. Cardiovascular implants are often used in both surgery and interventional cardiology. Cardiovascular stents are utilized in percutaneous coronary interventions (PCI), and are classified as either bare metal stents (BMS) or drug-eluting stents (DES). Although DES might decrease the risk of vascular restenosis, there are complications (e.g. thrombosis) associated with it as well. Many new and novel composite materials are increasingly being developed along the premise of mobilizing and attracting endogenous stem cells to home-in and differentiate into a confluent layer of endothelial cell around the vessel wall. One of the main forces acting on cells in a blood vessel wall is fluid shear stress. Fluid shear stress is vital in establishing the vasculature of the embryo, and different shear stress patterns have been both implicated in maintaining vascular physiology, and also associated with certain pathological conditions. Recent evidence suggests that via a plethora of mechanosensors and mechanotransduction signaling pathways, stem cells differentiate into endothelial cells when exposed to fluid shear stress. Here we review the current knowledge pertaining to the roles that mechanosensors and mechanotransducers play in stem cell differentiation into endothelial cells via fluid shear stress, and its implications for pharmacological applications and cardiovascular implants in the realm of regenerative medicine.     

应用西罗莫司药物洗脱支架治疗老年冠心病的疗效观察

目的 探讨国产西罗莫司药物洗脱支架在老年冠心病患者中应用的疗效和安全性.方法 对在该院接受国产西罗莫司药物洗脱支架Firebird治疗的107例老年冠心病患者,观察术后即刻效果、住院期间并发症及6个月随访结果.结果 成功植入175个Firebird支架,支架植入即刻成功率98.9%,住院期间支架内血栓1例(0.9%)致死亡,随访6个月,无心肌梗死、死亡发生,复发心绞痛6例,支架再狭窄发生率为2.6%,6个月主要心脏不良事件(MACE)发生率为2.8%.结论 老年冠心病患者应用国产西罗莫司药物洗脱支架安全有效.     

应用西罗莫司药物洗脱支架治疗老年冠心病的疗效观察

目的 探讨国产西罗莫司药物洗脱支架在老年冠心病患者中应用的疗效和安全性.方法 对在该院接受国产西罗莫司药物洗脱支架Firebird治疗的107例老年冠心病患者,观察术后即刻效果、住院期间并发症及6个月随访结果.结果 成功植入175个Firebird支架,支架植入即刻成功率98.9%,住院期间支架内血栓1例（0.9%）致死亡,随访6个月,无心肌梗死、死亡发生,复发心绞痛6例,支架再狭窄发生率为2.6%,6个月主要心脏不良事件（MACE）发生率为2.8%.结论 老年冠心病患者应用国产西罗莫司药物洗脱支架安全有效.     

应用西罗莫司药物洗脱支架治疗老年冠心病的疗效观察

目的 探讨国产西罗莫司药物洗脱支架在老年冠心病患者中应用的疗效和安全性.方法 对在该院接受国产西罗莫司药物洗脱支架Firebird治疗的107例老年冠心病患者,观察术后即刻效果、住院期间并发症及6个月随访结果.结果 成功植入175个Firebird支架,支架植入即刻成功率98.9%,住院期间支架内血栓1例(0.9%)致死亡,随访6个月,无心肌梗死、死亡发生,复发心绞痛6例,支架再狭窄发生率为2.6%,6个月主要心脏不良事件(MACE)发生率为2.8%.结论 老年冠心病患者应用国产西罗莫司药物洗脱支架安全有效.     

药物洗脱支架置入对糖尿病并发冠心病患者不良心血管事件的影响

目的评价药物洗脱支架置人对糖尿病并发冠心病患者不良事件的影响。方法对600例行药物洗脱支架植入术的患者进行随访,其中糖尿病患者147例。通过随访术后主要不良心血管事件（包括死亡,非致死性心肌梗死,再次靶病变血运重建和再次靶血管血运重建）和支架内再狭窄的发生率评价药物洗脱支架在糖尿病患者中的疗效。结果糖尿病患者和非糖尿病患者术后的主要不良心血管事件（7．9％与4．9％,P=0．344）和支架内再狭窄（6．0％与4．9％,P=0．540）发生率之间差异元统计学意义。糖尿病患者植入Cypher和TAXUS支架后主要不良心血管事件（7．9％与4．9％,P=0．344）和支架内再狭窄（1．4％与1．9％,P=1．000）发生率之间差异无统计学意义。结论糖尿病患者使用药物洗脱支架是安全有效的,且Cypher和TAXUS两种支架在糖尿病患者中疗效差异无统计学意义。     

Clinical experience and applications of drug-eluting stents in the noncoronary vasculature, bile duct and esophagus

OBJECTIVE: To review the use of drug-eluting stents outside the coronary artery. FINDINGS: The vast majority of research and clinical data on drug-eluting stents are from their use in coronary artery atherosclerosis; however, these devices can be used outside the coronary circulation in both vascular and nonvascular structures. In noncoronary arteries the principle indication for drug-eluting vascular stents is the same as in the coronary circulation, prevention of restenosis. Human experience has been essentially limited to trials or compassionate use; two small controlled studies and a number of small observational single center reports have been published, and there are trials in progress. To date the data have not been as compelling as in the coronary circulation. The physical characteristics of each vascular bed such as external compressive forces, blood flow rates, wall thickness relative to lumen size, and vessel wall composition differ significantly from the coronary circulation and each presents unique challenges to local drug delivery. Outside the vascular bed, the principle expected use is the prevention of tissue ingrowth after stent insertion in tubular structures such as the trachea, esophagus or bile ducts. CONCLUSIONS: Considerable further study of drug-eluting stents will be required in each anatomic region to determine the ideal stent/drug combination and clinical appropriateness.