High P-selectin expression and low CD36 occupancy on circulating platelets are strong predictors of restenosis after coronary stenting in patients with coronary artery disease

Recent studies have shown that circulating platelets play an important role in the development of restenosis early after coronary stent implantation. We investigated P-selectin expression and CD36 blockade on platelets by flow cytometry in 48 consecutive patients who underwent coronary stenting. P-selectin expression was significantly higher 1 day after stenting in patients who had restenosis (n = 15) than in those who had no restenosis (n = 28), and the odds ratio for restenosis in patients with high P-selectin levels (MFI > 6.5) was 11.67 (P < 0.001) as compared with patients who had intermediate and low P-selectin levels. CD36 blockade was assessed with the use of two anti-CD36 antibodies, OKM5 and GS95 (our new anti-CD36 antibody), the binding of which indicates total CD36 amount and free CD36 unoccupied by lipid-related ligands, respectively. Binding of OKM5 to platelets was similar before and after stenting in both groups. CD36 blockade on platelets was seen 1 day after stenting in the non-restenosis group, and the odds ratio for restenosis in patients without CD36 blockade [GS95 binding ratio >0.8 as compared with binding before stenting] on day 1 was 28.60 (P < 0.001). P-selectin expression and unoccupied CD36 on platelets shortly after stenting may be strong predictors of post-stent restenosis.     

Predicting neointimal hyperplasia in stented arteries using time-dependant computational fluid dynamics: A review

This paper reviews the recent literature regarding the time-dependant computational fluid dynamics (CFD) analyses of blood flow through implanted coronary stents. The in vivo processes which result in arterial restenosis are identified. The definition and range of the computationally predicted variables which are believed to stimulate the restenosis processes are evaluated. The reviewed literature is subdivided into effect-based in which the effects of altering the flow model are investigated and design-based in which different geometric stent configurations are compared. Finally, conclusions are made regarding the body of work reviewed and recommendations are provided for future work in this field.     

XS0601对猪冠脉球囊损伤后内膜细胞凋亡及bcl-2、p53基因表达的影响

目的观察XS0601(由川芎和赤芍的有效部位组成)对猪冠状动脉球囊损伤后细胞凋亡及相关基因bcl-2、野生型p53表达的影响.方法球囊扩张损伤猪冠状动脉左前降支(LAD)中段内膜的方法建立再狭窄(RS)模型.其中对照组不给予特殊药物治疗,各药物组于术前2天开始给药,持续至术后4周处死.原位杂交方法观察球囊损伤后内膜中bcl-2、p53mRNA表达,原位末端标记法(ISEL)检测内膜中的凋亡细胞,并研究药物对细胞凋亡的影响.结果损伤后4周动脉在内弹力板(IEL)断裂情况下,形成了明显的新生内膜.小剂量和大剂量XS0601均可增加内膜中的凋亡细胞,其凋亡细胞阳性表达面积率与对照组相比差异有显著性(P<0.01和P<0.05);并能减少内膜中的bcl-2阳性杂交颗粒,增加p53阳性杂交颗粒.结论猪冠状动脉球囊损伤后新生内膜中的细胞凋亡水平较低,凋亡抑制基因bcl-2的表达增加.XS0601可通过减少凋亡抑制基因bcl-2的表达,上调凋亡促进基因p53的表达,从而对猪冠状动脉球囊损伤后SMC增殖过程中较低的凋亡水平进行调控,诱导新生内膜中的细胞凋亡.     

Laser angioplasty versus balloon angioplasty: The need for imaging

The current state of clinical laser angioplasty is reviewed. Compared to balloon dilation at the beginning of the past decade, both peripheral and coronary laser angioplasty devices produce better results. Compared to current balloon angioplasty techniques, however, laser angioplasty does not seem to offer improved initial or long term results. Intravascular ultrasound imaging may help to improve laser ablation of atherosclerotic plaque. It remains to be established, however, whether precise debulking of the obstruction will result in a reduced restenosis rate compared to balloon angioplasty.     

Starplasty: an ideal method for correction of occluded external nares following burns.

Correction of any closed ostium following either burns or any other trauma by release and split skin grafting is not very successful in the long run because of restenosis of the ostium by contraction of the graft. It is very difficult to maintain the patency by any kind of prosthesis. For this reason we have devised a new technique called 'starplasty', which is simple and effective in opening occluded external nares without any chances of restenosis.     

可降解外支架预防高脂血症兔自体移植静脉再狭窄

目的探讨在高脂内环境下聚乙醇酸(PGA)可降解血管外支架对自体移植静脉(VG)再狭窄的防治作用。方法建立高脂血症(HLP)兔颈内静脉-颈动脉移植模型,实验组VG应用PGA外支架保护,而对照组VG无外支架保护;分别于术前和术后4、8、12、20周获取VG,比较两组VG的再狭窄率及其内皮型一氧化氮合酶(eNOS)蛋白表达、一氧化氮(NO)生成量和组织形态变化的差异。结果对照组有4支VG出现再狭窄,而实验组无再狭窄。术后实验组VG与对照组比较:eNOS蛋白表达、NO生成量显著升高(P<0.05),脂质沉积明显减轻,内皮完整性较好,术后12、20周内、中膜增厚显著减轻(P<0.05)。结论高脂内环境下PGA外支架可有效预防VG再狭窄,作用可持续至外支架降解后。其机制与外支架保护和改善内皮功能,抑制VG的非适应性重塑有关。     

Stented artery biomechanics and device design optimization

The deployment of a vascular stent aims to increase lumen diameter for the restoration of blood flow, but the accompanied alterations in the mechanical environment possibly affect the long-term patency of these devices. The primary aim of this investigation was to develop an algorithm to optimize stent design, allowing for consideration of competing solid mechanical concerns (wall stress, lumen gain, and cyclic deflection). Finite element modeling (FEM) was used to estimate artery wall stress and systolic/diastolic geometries, from which single parameter outputs were derived expressing stress, lumen gain, and cyclic artery wall deflection. An optimization scheme was developed using Lagrangian interpolation elements that sought to minimize the sum of these outputs, with weighting coefficients. Varying the weighting coefficients results in stent designs that prioritize one output over another. The accuracy of the algorithm was confirmed by evaluating the resulting outputs of the optimized geometries using FEM. The capacity of the optimization algorithm to identify optimal geometries and their resulting mechanical measures was retained over a wide range of weighting coefficients. The variety of stent designs identified provides general guidelines that have potential clinical use (i.e., lesion-specific stenting).     

生物可降解性血管内支架及药物释放支架的研制

目的探讨采用溶液中加入药物的方法制作雷帕霉素释放BES的可行性及载药量准确性;明确裸BES、雷帕霉素释放BES及ASODN涂层BES与金属支架在力学性能方面的差异。方法应用高分子材料PLLA制作生物可降解血管内支架;采用溶液中加入药物的方法制作生物可降解雷帕霉素释放支架;采用表面涂层方法制作生物可降解反义寡核苷酸涂层支架。应用HPLC法对雷帕霉素释放BES的载药量进行检测。对三种支架进行径向支撑力测试并与金属支架比较。结果制作出BES基杆直径为0.5mm,扩张后直径为4.5或5.0mm,长度均为15mm。三种BES外观无明显区别;雷帕霉素释放BES平均载药量为181.4μg,与支架制作过程中的设计载药量基本一致;支撑力测试结果表明:三种PLLA支架径向支撑力略低于金属支架;裸BES与涂层BES径向支撑力相似,略高于雷帕霉素BES。结论生物可降解材料PL-LA制作的裸支架、载药支架及涂层支架的径向支撑力均略低于金属支架,载药支架径向支撑力略低于裸支架及表面涂层支架。溶液中加入雷帕霉素的方法含量可靠,可以代替支架表面多孔构型的加工工艺。     

降钙素基因相关肽对大鼠主动脉内皮剥脱的保护作用

为研究降钙素基因相关肽在防止动脉内膜损伤后平滑肌细胞增殖所致再狭窄中的作用机制，采用内皮剥脱、血管条灌流和放射免疫测定法测定了环磷一酸尿苷、降钙素基因相关肽和内皮素水平。结果发现，内皮剥脱后两周，血浆及主动脉组织降钙素基因相关肽含量增加（前者对照组为9．2±1．7，去内皮组为14．1±2．0ng／L；后者对照组为7．4±1．4，去内皮组为12．2±2．0ng／g）。应用外源性降钙素基因相关肽（25μg/Kg）可明显改善损伤血管对乙酰胆碱的内皮依赖性舒张反应；促进去内皮血管壁一氧化氮的合成；增加主动脉组织内cGMP的含量（对照组4．4±0．5，去内皮组2．0±0．5，降钙素基因相关肽组3．3±0．5ng/g；P＜0．01），减少内皮素的生成（P＜0．01），抑制损伤部位的内膜过度憎生（P＜0．01）．提示外源性降钙素基因相关肽可通过促进内皮的修复、抑制内膜的过度增殖而防止剥脱血管的再狭窄。     

Can Aggressive Lipid Lowering Using Low-Density Lipoprotein Apheresis Prevent Restenosis After Percutaneous Transluminal Coronary Angioplasty in Patients with Normocholesterolemia?

Abstract: We examined whether aggressive lipid lowering using low-density lipoprotein (LDL) apheresis could prevent restenosis after percutaneous transluminal coronary angioplasty (PTCA). Fifteen patients with 17 lesions underwent LDL apheresis once within a week before and after PTCA and thereafter every 2 or 3 weeks (apheresis group) for about 4 months. The control group consisted of 17 patients with 17 lesions. No patients received additional lipid lowering drugs after PTCA. In the apheresis group, the time interval means of the total and LDL cholesterol levels were significantly lower than those in the control group whereas no significant differences were found between the 2 groups regarding the mean percent diameter stenosis or minimal lumen diameter before and after PTCA and at follow-up. The restenosis rate was 29.4% in the apheresis group and 47.1% in the control group. The restenosis rate tended to be slightly lower in the apheresis group. The overall results, however, indicated that aggressive lipid lowering does not prevent restenosis.