全降解聚合物血管内支架植入后的力学微环境变化与MGF*

动脉粥样硬化作为一种主要的心血管疾病,威胁着全世界人类的健康. 全降解聚合物血管内支架是由生物可降解的高分子聚合物材料制作的用于治疗动脉粥样硬化病变变窄管腔的血管支架. 它克服了金属药物洗脱支架引起的慢性局部炎症反应、血管生理舒缩功能缺失和晚期支架内血栓形成以及未来可能在同一位置再次植入支架的缺陷. 但全降解聚合物支架由于各级降解产物的刺激引起炎症反应以及支架植入部位力学微环境的变化,从而引起支架内再狭窄和血栓形成,结合力生长因子(mechano growth factor, MGF)对力学刺激敏感的特性,MGF可能对心血管支架植入引起的局部力学变化作出响应. 因此本文对全降解聚合物支架植入后支架的降解特性与力学微环境变化引起的再狭窄、血栓形成等不良反应,以及MGF在其中的作用和研究进展进行了综述,以期为临床冠脉介入支架治疗提供参考.     

骨髓间充质干细胞捕获支架对犬冠状动脉再狭窄影响的研究

目的:观察骨髓间充质(MSCs)干细胞捕获支架能否预防和减少犬冠状动脉支架植入术后再狭窄.方法:①用乙基纤维素作为包被底物对支架进行包被,然后再包被骨髓间充质干细胞抗体.②以球囊损伤法建立犬冠状动脉狭窄模型,应用标准球囊导管技术,将包被有抗体的支架植入犬(n=20)冠状动脉前将支损伤段远端,再以相同方法在损伤段近端植入裸支架作为对照组(n=20).4w后处死动物,取出支架段血管行血管内超声(IVUS)及血管形态学检测分析血管管腔面积和内膜增生面积.结果:术后4周,骨髓间充质干细胞捕获支架组较裸支架组的最小管腔直径和新生内膜面积较明显减少(P<0.05),而最小管腔面积则明显增加(P<0.05).结论:骨髓间充质干细胞捕获支架能快速修复损伤的血管内膜,降低再狭窄的发生.     

血管内支架和支架内皮化

简要介绍了血管内支架产生的背景、发展进程及其应用于临床后出现的再狭窄问题,着重综述了十几年来内皮细胞种植血管内支架预防术后再狭窄的相关研究成果。血管内支架内皮化的最终实现可以使现行的血管支架具有正常血管内皮的生物相容性及生理功能,是控制支架植入术后再狭窄问题的很有前途的支架改进方法。     

血管内支架成形术治疗大脑中动脉狭窄

目的:探讨血管内支架成形术治疗大脑中动脉狭窄的疗效及安全性.方法:对22例大脑中动脉狭窄患者行血管内支架成形术,回顾性分析其临床特点、疗效及治疗经验.结果:22例患者共植入22枚支架,均获得成功.术后即刻造影狭窄率为(11.2±4.5)%,较术前(79±15)%明显改善.术后残余狭窄程度均小于20%.临床随访无TIA发作或脑卒中再发,DSA随访除1例外均无再狭窄发生.结论:血管内支架成形术治疗大脑中动脉狭窄安全有效,但远期疗效还需进一步观察.     

DES早期支架内血栓的形成和防治

目前,冠状动脉内支架植入术是冠心病血运重建的主要方法,支架置入可显著减少再狭窄和靶血管血运重建.虽然支架术后支架内血栓形成少见,但预后差,临床上可表现为急性心肌梗死或猝死.是药物洗脱支架的潜在危险,预防支架内血栓形成是冠状动脉粥样硬化性心脏病介入领域的研究热点和难点,因此,支架内血栓的形成、防治问题仍然值得我们关注与探讨.本文阐明了早期支架内血栓的影响因素,预防,观察方法及治疗措施.使用新一代的药物洗脱支架有望减少支架内血栓的发生.     

磷铵两性离子改性血管脱细胞支架可以有效体外抗血栓和内皮化

由于自体血管(由同一受体的血管用于血管移植材料)的有限可用性,以及非自体血管(人工制成的血管移植材料)的生长能力不足,组织工程血管越来越受到重视。文中构建了一种磷铵两性离子改性的血管脱细胞支架附以高度生物相容的骨髓源内皮祖细胞为内层的新型血管移植材料。通过一种简便的方法——共沉淀法改性血管脱细胞支架,评价其体外血小板粘附实验、溶血实验、复钙实验和细胞毒性等相关指标。磷铵两性离子改性后抗凝血活性提高,可以有效地促使类似于天然血管腔表面凹凸结构的脱细胞支架表面内皮祖细胞的附着。改性后的脱细胞支架具有与天然血管相似的力学性能,在体外可以有效地构建内皮化。研究结果为血管脱细胞支架通过改性实现体外抗血栓和内皮化方面进行了初步探索。     

冠状动脉支架血流动力学中的几个问题

由于冠状动脉支架介入治疗具有手术创伤小、操作简单、见效快、病人恢复时间短等诸多优点,在治疗心血管动脉粥样硬化或血栓堵塞方面,有逐渐替代外科搭桥手术的趋势。虽然血管支架技术在临床已经有广泛应用,治疗效果也有明显的改善,但是依然存在许多不足需要改进。本文首先回顾了血管支架的发展历程,然后针对血管支架研究中与血流动力学相关的几个待解决的问题进行了论述,以期从血流动力学的角度为血管支架的改进和发展提出建议。     

可吸收血管支架临床试用效果良好

血管支架是一种植入血管狭窄性病变区的金属丝网管状器械,用于治疗冠心病等血管性疾病,进行血管重建手术的植入器械,可支撑动脉血管开启的作用。目前应用的是裸金属支架和药物涂层支架,这两种支架都有导致血栓等风险的缺陷。     

孤立性肠系膜上动脉夹层介入血管腔内治疗的初步体会

目的:评价介入血管腔内治疗孤立性肠系膜上动脉夹层(ISMAD)的安全性和疗效.方法:5例患者均通过腹部CT及血管造影明确诊断ISMAD,本组病例确诊后行介入血管腔内治疗,术后继予抗凝抗血小板治疗,并术后1、3、6个月进行CTA或血管造影随访.结果:5例患者手术成功率100％,其中支架联合弹簧圈栓塞2例,双支架重叠技术3例,无并发症发生.全部患者术后3周内症状逐渐消失;术后3～6个月时肠系膜上动脉CTA及血管造影显示动脉瘤腔不显影,支架腔内血流通畅;随访3～12个月(平均7.8个月)夹层动脉瘤无复发.结论:介入血管腔内治疗是治疗ISMAD的安全有效的方法.     

形状记忆合金超弹性自扩张血管支架的优化设计

自扩张型镍钛合金血管支架由于其良好的生物相容性与超弹性,可以很好地解决支架植入后的再狭窄问题。利用有限元软件ANSYS对支架在血管中的自扩张行为进行模拟,并对支架的网格形状与尺寸进行优化设计。     

Fabrication and in vitro deployment of a laser-activated shape memory polymer vascular stent

Background

Vascular stents are small tubular scaffolds used in the treatment of arterial stenosis (narrowing of the vessel). Most vascular stents are metallic and are deployed either by balloon expansion or by self-expansion. A shape memory polymer (SMP) stent may enhance flexibility, compliance, and drug elution compared to its current metallic counterparts. The purpose of this study was to describe the fabrication of a laser-activated SMP stent and demonstrate photothermal expansion of the stent in an in vitro artery model.

Methods

A novel SMP stent was fabricated from thermoplastic polyurethane. A solid SMP tube formed by dip coating a stainless steel pin was laser-etched to create the mesh pattern of the finished stent. The stent was crimped over a fiber-optic cylindrical light diffuser coupled to an infrared diode laser. Photothermal actuation of the stent was performed in a water-filled mock artery.

Results

At a physiological flow rate, the stent did not fully expand at the maximum laser power (8.6 W) due to convective cooling. However, under zero flow, simulating the technique of endovascular flow occlusion, complete laser actuation was achieved in the mock artery at a laser power of ~8 W.

Conclusion

We have shown the design and fabrication of an SMP stent and a means of light delivery for photothermal actuation. Though further studies are required to optimize the device and assess thermal tissue damage, photothermal actuation of the SMP stent was demonstrated.     

Influence of plaque calcifications on coronary stent fracture: A numerical fatigue life analysis including cardiac wall movement

Coronary stent fracture is still an unresolved issue in the field of minimally invasive cardiovascular interventions due to its high rate of incidence and uncertain clinical consequences. Recent studies, based on clinical data, proved that there are several factors which can be identified as independently responsible of coronary stent fracture. Among these, calcifications, which increase the local stiffness and heterogeneity of atherosclerotic plaques, seem to play a major role. From a mechanical point of view, stent fracture in coronary arteries is triggered by the cyclic loading of pulsatile blood pressure combined with the movement of cardiac wall.     

Assessment of mechanical integrity for drug-eluting renal stent with micro-sized drug reservoirs

The drug-eluting stent (DES) has become the gold standard worldwide for the treatment of cardiovascular diseases. In recent years, an innovative variation of the DES with micro-sized drug reservoirs has been introduced. It allows programmable drug delivery with both spatial and temporal control and has several potential advantages over traditional DESs. However, creating such reservoirs on the stent struts may weaken the structure of the stent scaffolding and compromise its mechanical integrity. In this study, we propose to use this innovative stent concept in the renal indication for potential treatment of both renal artery stenosis (upstream) and its associated kidney diseases (downstream) at the same time. The effects of these micro-sized drug reservoirs on several key clinically relevant functional attributes of the drug-eluting renal stent were systematically and quantitatively investigated. Finite element models were developed to predict the mechanical integrity of a balloon-expandable stent at various stages. Results show that (1) creating drug reservoirs on a stent could impact the stent fatigue resistance to certain degrees; (2) drug reservoirs on the stent crowns lead to greater loss in all key stent attributes than reservoirs on either bar arms or connectors and (3) the proposed optimised depot stent was proven to be feasible and could triple drug capacity than the current DESs, with marginal trade-off in its key clinical attributes. These results can serve as the guidelines to help future stent designs to achieve the best combination of stent structural integrity and smart drug delivery in the future.     

A Murine Model of Stent Implantation in the Carotid Artery for the Study of Restenosis

Despite the considerable progress made in the stent development in the last decades, cardiovascular diseases remain the main cause of death in western countries. Beside the benefits offered by the development of different drug-eluting stents, the coronary revascularization bears also the life-threatening risks of in-stent thrombosis and restenosis. Research on new therapeutic strategies is impaired by the lack of appropriate methods to study stent implantation and restenosis processes. Here, we describe a rapid and accessible procedure of stent implantation in mouse carotid artery, which offers the possibility to study in a convenient way the molecular mechanisms of vessel remodeling and the effects of different drug coatings.     

Lowering Cardiovascular Disease Risk for People with Severe Mental Illnesses in Primary Care: A Focus Group Study

Background

People with severe mental illnesses die early from cardiovascular disease. Evidence is lacking regarding effective primary care based interventions to tackle this problem.

Aim

To identify current procedures for, barriers to, and facilitators of the delivery of primary care based interventions for lowering cardiovascular risk for people with severe mental illnesses.

Method

75 GPs, practice nurses, service users, community mental health staff and carers in UK GP practice or community mental health settings were interviewed in 14 focus groups which were audio-recorded, transcribed and analysed using Framework Analysis.

Results

Five barriers to delivering primary care based interventions for lowering cardiovascular risk in people with severe mental illnesses were identified by the groups: negative perceptions of people with severe mental illnesses amongst some health professionals, difficulties accessing GP and community-based services, difficulties in managing a healthy lifestyle, not attending appointments, and a lack of awareness of increased cardiovascular risk in people with severe mental illnesses by some health professionals. Identified facilitators included involving supportive others, improving patient engagement with services, continuity of care, providing positive feedback in consultations and goal setting.

Conclusion

We identified a range of factors which can be incorporated in to the design, delivery and evaluation of services to reduce cardiovascular risk for people with severe mental illnesses in primary care. The next step is determining the clinical and cost effectiveness of primary care based interventions for lowering cardiovascular risk in people with severe mental illnesses, and evaluating the most important components of such interventions.     

Salt intake and mental distress among rural community-dwelling Japanese men

Background

Activated mineralocorticoid receptors influence the association between daily salt intake and blood pressure. A relatively low mineralocorticoid receptor function is reported to be a risk for mental distress such as depression. Since mental distress is also a known risk for hypertension and cardiovascular disease, understanding of the association between estimated daily salt intake and mental distress contributing to hypertension is important for risk estimation for cardiovascular disease. However, no single study has reported this association.

Methods

We conducted a cross-sectional study of 1014 Japanese men undergoing general health check-ups. Mental distress was diagnosed as a Kessler 6 scale score ≥5. We also classified mental distress by levels of hypertension. Estimated daily salt intake was calculated from a causal urine specimen.

Results

Independent from classical cardiovascular risk factors and thyroid disease, we found a significant inverse association between estimated daily salt intake and mental distress. When we analyzed for mental distress and hypertension, we also found a significant association. With the reference group being the lowest tertiles of estimated daily salt intake, the multivariable odds ratios (ORs) of mental distress and mental distress with hypertension for the highest tertiles were 0.50 (0.29–0.88) and 0.46 (0.22–0.96).

Conclusions

Lower estimated daily salt intake is a significant risk of mental distress for rural community-dwelling Japanese men. Since depression is reported to be associated with cardiovascular disease, risk estimation for the lower intake of salt on mental distress, especially for mental distress with hypertension, may become an important tool to prevent cardiovascular disease.     

Stent‐mediated gene and drug delivery for cardiovascular disease and cancer: A brief insight

This review concisely recapitulates the different existing modes of stent‐mediated gene/drug delivery, their considerable advancement in clinical trials and a rationale for other merging new technologies such as nanotechnology and microRNA‐based therapeutics, in addition to addressing the limitations in each of these perpetual stent platforms. Over the past decade, stent‐mediated gene/drug delivery has materialized as a hopeful alternative for cardiovascular disease and cancer in contrast to routine conventional treatment modalities. Regardless of the phenomenal recent developments achieved by coronary interventions and cancer therapies that employ gene and drug‐eluting stents, practical hurdles still remain a challenge. The present review highlights the limitations that each of the existing stent‐based gene/drug delivery system encompasses and therefore provides a vision for the future with respect to discovering an ideal stent therapeutic platform that would circumvent all the practical hurdles witnessed with the existing technology. Further study of the improvisation of next‐generation drug‐eluting stents has helped to overcome the issue of restenosis to some extent. However, current stent formulations fall short of the anticipated clinically meaningful outcomes and there is an explicit need for more randomized trials aiming to further evaluate stent platforms in favour of enhanced safety and clinical value. Gene‐eluting stents may hold promise in contributing new ideas for stent‐based prevention of in‐stent restenosis through genetic interventions by capitalizing on a wide variety of molecular targets. Therefore, the central consideration directs us toward finding an ideal stent therapeutic platform that would tackle all of the gaps in the existing technology.     

Optimization of cardiovascular stent design using computational fluid dynamics

Coronary stent design affects the spatial distribution of wall shear stress (WSS), which can influence the progression of endothelialization, neointimal hyperplasia, and restenosis. Previous computational fluid dynamics (CFD) studies have only examined a small number of possible geometries to identify stent designs that reduce alterations in near-wall hemodynamics. Based on a previously described framework for optimizing cardiovascular geometries, we developed a methodology that couples CFD and three-dimensional shape-optimization for use in stent design. The optimization procedure was fully-automated, such that solid model construction, anisotropic mesh generation, CFD simulation, and WSS quantification did not require user intervention. We applied the method to determine the optimal number of circumferentially repeating stent cells (N(C)) for slotted-tube stents with various diameters and intrastrut areas. Optimal stent designs were defined as those minimizing the area of low intrastrut time-averaged WSS. Interestingly, we determined that the optimal value of N(C) was dependent on the intrastrut angle with respect to the primary flow direction. Further investigation indicated that stent designs with an intrastrut angle of approximately 40 deg minimized the area of low time-averaged WSS regardless of vessel size or intrastrut area. Future application of this optimization method to commercially available stent designs may lead to stents with superior hemodynamic performance and the potential for improved clinical outcomes.     

Analyses and design of expansion mechanisms of balloon expandable vascular stents

Vascular stents are expanded in blood vessels with lumens larger than their cardiac counterparts. Extreme radial expansion significantly reduces the expanded length of some designs, resulting in insufficient lesion coverage and inaccurate placement. It is hypothesized that expansion mechanisms of a balloon-expandable stent, driven by plastic hinges, are controlled by the cell topology. This hypothesis is first tested for stent expansion using kinematic and kinetic analyses, followed by more detailed finite element (FE) calculations. Three balloon-expandable stent designs are laser micro-machined for experimental verification of the length–diameter relations predicted by the analytical and FE models. It is found that stent designs with positive, negative, or zero foreshortening over expansion phase can be designed by tailoring unit cell geometries and hence obtain desired length–diameter and pressure–diameter characteristics.