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。     

Predictors of midterm high-grade restenosis after carotid revascularization in a multicenter national database

BackgroundRestenosis after carotid revascularization is clinically challenging. Several studies have looked into the management of recurrent restenosis; however, studies looking into factors associated with restenosis are limited. This study evaluated the predictors of restenosis after carotid artery stenting (CAS) and carotid endarterectomy (CEA) using a large national database.MethodsPatients undergoing CEA or CAS in the Vascular Quality Initiative data set (2003-2016) were analyzed. Patients with no follow-up (33%) and those who had prior ipsilateral CEA or CAS were excluded. Significant restenosis was defined as ≥70% diameter-reducing stenosis, target artery occlusion or peak systolic velocity ≥300 cm/s, or repeated revascularization. Kaplan-Meier survival analysis and bootstrapped Cox regression models with stepwise forward and backward selection were used.ResultsA total of 35,720 procedures were included (CEA, 31,329; CAS, 4391). No significant difference in restenosis rates was seen between CEA and CAS at 2 years (7.7% vs 9.4% [P = .09]; hazard ratio [HR], 0.99; 95% confidence interval [CI], 0.79-1.25; P = .97). However, after adjustment for age, sex, and symptomatic status at the time of the index operation, CAS patients who had postoperative restenosis were more likely to have a symptomatic presentation (odds ratio, 2.2; 95% CI, 1.2-4.0; P = .01) and to undergo repeated revascularization at 2 years (HR, 1.75; 95% CI, 1.3-2.4; P < .001) compared with patients who had restenosis after CEA. Predictors of restenosis after CAS included a common carotid artery lesion (HR, 1.65; 95% CI,1.06-2.57; P = .03), whereas age (HR, 0.91; 95% CI, 0.84-0.99; P = .03) and dilation after stent placement (HR, 0.53; 95% CI, 0.39-0.72; P < .001) were associated with decreased restenosis at 2 years. Predictors of restenosis after CEA included female sex (HR, 1.55; 95% CI, 1.38-1.74; P < .001), prior neck irradiation (HR, 2.35; 95% CI, 1.66-3.30; P < .001), and prior bypass surgery (HR, 1.29; 95% CI, 1.01-1.65; P = .04). On the other hand, factors associated with decreased restenosis after CEA included age (HR, 0.95; 95% CI, 0.92-0.98; P < .001), black race (HR, 0.57; 95% CI, 0.37-0.89; P = .01), patching (HR, 0.61; 95% CI, 0.47-0.79; P < .001), and completion imaging (HR, 0.70; 95% CI, 0.52-0.95; P = .02).ConclusionsOur results show no significant difference in restenosis rates at 2 years between CEA and CAS. Restenosis after CAS is more likely to be manifested with symptoms and to undergo repeated revascularization compared with that after CEA. Poststent ballooning after CAS and completion imaging and patching after CEA are associated with decreased hazard of restenosis; however, further research is needed to assess longer term outcomes and to balance the risks vs benefits of certain practices, such as poststent ballooning.     

化瘀通脉颗粒干预经皮腔内冠状动脉介入治疗术后再狭窄的临床研究

目的观察化瘀通脉颗粒干预冠心病经皮腔内冠状动脉介入治疗(PCI)术后再狭窄的临床效果。方法将60例冠心病经PCI治疗患者随机分为对照组和治疗组,治疗组31例,对照组29例。对照组按照常规治疗方法治疗,治疗组在对照组药物基础上加服化瘀通脉颗粒治疗。两组疗程均为6个月。结果治疗组总有效率为83.87%,明显高于对照组的62.07%(P0.05)。治疗组中医症状积分降低较对照组更加明显(P0.05)。治疗组心绞痛和临床再狭窄人数明显少于对照组(P0.05);冠脉CTA再狭窄发生人数治疗组也少于对照组(P0.05)。结论化瘀通脉颗粒具有预防PCI术后再狭窄的作用。     

MMP_2和MMP_9在损伤血管中的原位表达

目的探讨基质金属蛋白酶在血管损伤后的改变及可能作用。方法在大鼠胸主动脉球囊损伤的模型上，应用原位杂交的方法，观察了MMP2、MMP9在血管损伤后不同时间的表达情况。结果MMP2在球囊损伤后第三天开始表达，第7天达高峰，第14天未见表达，MMP9从第3天开始表达，并一直持续到14天，但第14天只有新生内膜部位有少量表达。结论MMP2、MMP9在血管损伤后，异常表达，可能与平滑肌细胞迁移、新生内膜形成及血管重塑有关。     

组织型纤溶酶原激活剂基因导入犬血管壁预防血管成形术后再狭窄

目的：组织型纤溶酶原激活剂（ｔ－ＰＡ）基因治疗，为防治血栓性疾病提供了一个可能全新的方法与前景。探索ｔ－ＰＡ基因转移至犬血管壁后基因表达持续的时限以及预防血管成行术后再狭窄的价值。方法：１８条家犬，其中对照组６条，另１２条在形成再狭窄模型时随机分为３０天、６０天和９０天３个观察亚组，每组４条犬，并用多孔球囊输注导管将携带ｔ－ＰＡ基因的逆转录病毒载体直接高压注入冠状动脉及股动脉壁。结果：经过３０天、６０天和９０天不同时间的观察，发现在脱氧核糖核酸（ＤＮＡ）水平（原位杂交、ＤＮＡ印迹）、转录水平［（信使核糖核酸（ｍＲＮＡ）点杂交］及产物水平（免疫组化）等方面均证实ｔ－ＰＡ基因的存在和活性产物表达，而且发现再狭窄组３个月时基因治疗组比对照组的百分狭窄面积小２２．２％。结论：ｔ－ＰＡ基因治疗有一定的预防血管成形术后再狭窄的作用     

Proliferation and C-myc Gene Expression of Smooth Muscle Cells in Rabbit Carotid Artery after Stenting

Objectives To investigate the proliferation of smooth muscle cells (VSMCs) and the expression of c-myc gene in rabbit carotid arteries after stenting. Methods Platinium-Iridium stent were implanted into the fight carotid arteries of 16 rabbits under vision. 7,14,30 and 90 days after the stenting procedure, morphological changes of VSMCs were observed under light and transmission electron microscope. The c-myc gene expression was detected by insitu hybridization (ISH) and immunohistochemical staining. Results 7 days after stenting, the phenotype of VSMCs changed from contractile to synthetic phenotype; there were a number of proliferative VSMCs in the neointima. At 14 and 30 days, there were synthetic and transitive VSMCs. At 90 days, the phenotype of VSMCs recovered to contractile phenotype. The ultrastructure of typical synthetic phenotype of VSMCs were round, containing a large amount of rough endoplasmic reticulum and mitochondria. Cmyc expression were positive both by ISH and im-munohistochemical staining. Conclusions C-myc gene expression increases and closely relates to VSMCs proliferation after stenting. It may play an important role in the in-stent restenosis.     

Transitioning from 16-slice to 64-slice multidetector computed tomography for the assessment of coronary artery disease: Are we really making progress?

BACKGROUND:

Multidetector computed tomography (MDCT) has demonstrated promise in the noninvasive evaluation of coronary artery disease.

OBJECTIVE:

To systematically review the literature regarding the improved diagnostic accuracy of 64-slice MDCT.

METHODS:

An EMBASE, OVID, PubMed and Cochrane Library database search was performed using the key words ‘computed tomography’ matched with the terms ‘coronary artery’ or ‘coronary angiography’ to identify English-language articles examining MDCT cardiac imaging. Studies that compared 16-slice or 64-slice MDCT with catheter-based coronary angiography for the detection of coronary artery disease in non-revascularized, poststent and post-coronary artery bypass graft patients were included. Data were pooled to obtain a weighted sensitivity, specificity and diagnostic accuracy for MDCT. Negative and positive predictive values, and likelihood ratios were calculated based on sensitivity and specificity.

RESULTS:

Currently, 15 studies involving 1008 patients have examined the efficacy of 64-slice MDCT in the assessment of coronary artery stenosis (more than 50% luminal narrowing). In these studies, 64-slice MDCT has demonstrated a sensitivity (89%), specificity (96%) and diagnostic accuracy (95%) similar to that of 16-slice MDCT. However, 64-slice MDCT was able to assess 5% more coronary artery segments than 16-slice MDCT. In revascularized patients, MDCT can accurately assess both bypass graft occlusion and stenosis. The 64-slice MDCT is also capable of adequately detecting in-stent restenosis. Improvements in spatial and temporal resolution with 64-slice technology have decreased the occurrence of high attenuation and motion artefacts that plagued the previous generation of MDCT scanners.

CONCLUSION:

MDCT offers an accurate assessment of the coronary arteries, stented arteries and bypass grafts. The improved accuracy and safety of MDCT may reduce the need for catheter-based coronary angiography.     

Late and very late catch-up after 90Sr/90Y beta-irradiation for the treatment of coronary in-stent restenosis

Since late vessel failure has been speculated as a significant limitation of vascular brachytherapy (VBT), we conducted a prospective clinical evaluation at 6, 12, 24, 36 and 60 months follow-up after irradiation with ⁹⁰Sr/⁹⁰Y for in-stent restenosis (ISR) regardless of the patient's symptomatic status. Complete five-year follow-up is reported for 104 consecutive patients. The cumulative rate of death was 13.5% (6 months: 0.96%; 12 months: 2.88%; 24 months: 4.81%; 36 months: 7.69%), of acute myocardial infarction 4.81% (2.88%; 4.81%; 4.81%; 4.81%), of late thrombotic occlusion 4.81% (3.85%; 4.81%; 4.81%; 4.81%), of target lesion revascularization (TLR) 27.9% (8.65%; 12.5%; 17.3%; 21.2%), of target vessel revascularization (TVR) 43.3% (12.5%; 19.2%; 22.1%; 29.8%), and of all major adverse cardiovascular events (MACE) 61.5% (16.3%; 26.9%; 31.7%; 42.3%), respectively. Considered that the annual incidence of TVR after the first year following drug-eluting stenting for in-stent restenosis has been reported as approximately 3% per year, an incidence of 5.8% per year following VBT of our study population clearly indicates a more pronounced, delayed and, even in the fifth year after the index procedure, ongoing restenotic process following beta-irradiation of in-stent restenotic |lesions associated with clinically relevant adverse cardiovascular events.     

Efficiency of Dispatch ® and Infiltrator ® Cardiac Infusion Catheters in Arterial Localization of Nanoparticles in a Porcine Coronary Model of Restenosis

Localized intramural delivery of sustained release biodegradable nanoparticles containing an antiproliferative agent could provide prolonged drug effect at the site of vascular injury that could inhibit the proliferation of smooth muscle cells and hence restenosis. The efficiency of arterial localization of nanoparticles is crucial in maximizing the drug effect in the target tissue. Therefore, the objective of the present study was to determine the comparative efficiency of the Dispatch ® and the Infiltrator ® cardiac infusion catheters to localize nanoparticles in the arterial wall. Following a standard balloon angioplasty procedure on the left anterior descending artery (LAD) in a porcine coronary model of restenosis, a suspension of nanoparticles containing a fluorescent marker was infused at the site of injury using either the Dispatch ® or the Infiltrator ® catheter. One hour following the infusion, animals were sacrificed and the nanoparticle levels in the LAD and other tissue were analyzed. The Dispatch ® catheter resulted in 3.3 folds greater efficiency of nanoparticle localization in the LAD than the Infiltrator ® catheter (309 ± 124 vs. 93 ± 43 μ g/g of tissue, n =6 for Dispatch ® and n =5 for Infiltrator ®, p =0.082, t -test). It is estimated that about 2% of the arterial volume can be displaced with the nanoparticle infusion. Fluorescence microscopy of the cross-sections of the LAD revealed greater fluorescence activity in the intimal layer with both the catheters, however the arteries infused using the Dispatch ® catheter demonstrated relatively higher degree of fluorescence activity in the medial and adventitial layers. The transmission electron microscopy of the arterial sections demonstrated infiltration of nanoparticles in the arterial wall and the histological analysis of the sections demonstrated no apparent damage to the endothelium due to the infusion of nanoparticles.