High-performance self-expanding stent graft: development and application to experimental aneurysms

Large or giant aneurysms in the craniocervical area with broad necks are of concern and are treated surgically, endovascularly, or in both ways. Surgically, their treatment is difficult, with relatively high risks. For their embolization, we have been developing a high-performance stent graft that has three characteristics: a thin and expandable segmented polyurethane (SPU) membrane, micropores formed by the excimer laser ablation technique, and a drug delivery system at the membrane. Stent grafts were fabricated using commercially available self-expanding stents. These stents were covered with a thin SPU membrane by the dip-coating method. Micropores were then formed by the excimer laser ablation technique and an argatroban coating was added. We tested the effectiveness of this new stent graft by treating experimental canine aneurysms. Experimental aneurysms were made in the bilateral carotid arteries of four female beagles by end-toside anastomosis using an autologous venous pouch. One month after aneurysm formation, the experimental aneurysm in one of the carotid arteries was covered with our self-expanding stent graft and the aneurysm in the other artery was covered with a bare self-expanding stent. On angiograms 1 month after stenting, the aneurysms treated with our stent graft were completely occluded without significant parent artery stenosis, but the aneurysms treated with the original bare stent were still open. Our high-performance self-expanding stent graft was easily applied to the experimental aneurysms and accomplished complete occlusion of aneurysms in beagles. Further study should be performed for the goal of clinical use. This work was presented in part at the 45th Annual Meeting of the Japanese society for Artificial Organs in Osaka     

Tissue Responses to Endovascular Stent Grafts for Saccular Abdominal Aortic Aneurysms in a Canine Model

We investigated tissue responses to endoskeleton stent grafts for saccular abdominal aortic aneurysms (AAAs) in canines. Saccular AAAs were made with Dacron patch in 8 dogs, and were excluded by endoskeleton stent grafts composed of nitinol stent and expanded polytetrafluoroethylene graft. Animals were sacrificed at 2 months (Group 1; n = 3) or 6 months (Group 2; n = 5) after the placement, respectively. The aortas embedding stent grafts were excised en bloc for gross inspection and sliced at 5 to 8 mm intervals for histopathologic evaluation. Stent grafts were patent in all except a dog showing a thrombotic occlusion in Group 2. In the 7 dogs with patent lumen, the graft overhanging the saccular aneurysm was covered by thick or thin thrombi with no endothelial layer, and the graft over the aortic wall was completely covered by neointima with an endothelial layer. Transgraft cell migration was less active at an aneurysm than at adjacent normal aorta. In conclusion, endoskeleton stent grafts over saccular aneurysms show no endothelial coverage and poor transgraft cell migration in a canine model.     

Neutrophil-derived cathelicidin protects from neointimal hyperplasia

Percutaneous transluminal angioplasty with stent implantation is used to dilate arteries narrowed by atherosclerotic plaques and to revascularize coronary arteries occluded by atherothrombosis in myocardial infarction. Commonly applied drug-eluting stents release antiproliferative or anti-inflammatory agents to reduce the incidence of in-stent stenosis. However, these stents may still lead to in-stent stenosis; they also show increased rates of late stent thrombosis, an obstacle to optimal revascularization possibly related to endothelial recovery. Here, we examined the contribution of neutrophils and neutrophilic granule proteins to arterial healing after injury. We found that neutrophil-borne cathelicidin (mouse CRAMP, human LL-37) promoted reendothelization and thereby limited neointima formation after stent implantation. We then translated these findings to an animal model using a neutrophil-instructing, biofunctionalized, miniaturized Nitinol stent coated with LL-37. This stent reduced in-stent stenosis in a mouse model of atherosclerosis, suggesting that LL-37 may promote vascular healing after interventional therapy.     

颅内宽颈动脉瘤合并载瘤血管重度狭窄的血管内治疗

目的:探讨颅内宽颈动脉瘤合并载瘤动脉重度狭窄血管内治疗的安全性及疗效。方法:回顾性研究。纳入郑州大学人民医院脑血管病科2017年1月—2019年12月采用血管内治疗颅内宽颈动脉瘤合并载瘤血管重度狭窄的患者14例,共14个动脉瘤。14例中,男5例、女9例,年龄45～76(61.07±10.43)岁;8例为破裂动脉瘤,6例...     

局麻下颅内动脉狭窄支架置入术的可行性研究

目的：探讨在清醒状态下颅内动脉狭窄支架置入术的可行性及临床意义。方法：2007年2月到2008年1月,在局麻下应用血管内支架置入术治疗颅内动脉狭窄患者12例,其中颈内动脉系狭窄7例,椎-基底动脉系狭窄5例。结果：本组12例均成功接受了血管内支架置入,术中患者清醒,配合良好,无不良反应。术后6个月复查DSA提示,颅内动脉狭窄程度由原来的67．5％±9．5％下降至9．5％±2．8％（P〈0．01）。随访12～23个月,12例患者症状均改善,无卒中发生。结论：局麻下行血管内支架置入术治疗颅内动脉狭窄,可将重要并发症的危险性降到最低;颅内动脉痛觉神经并不敏感,完全可以承受介入支架置入操作。     

颅内动脉狭窄支架置入与植入材料的生物相容性

背景：颅内动脉狭窄支架按照结构和材质可将血管内支架分为金属支架、聚合物支架、涂层支架等类型。那么哪一种支架更具临床应用价值呢？ 目的：对颅内动脉狭窄支架置入治疗的理论、应用、并发症及疗效进行评定,并分析植入材料的生物相容性。 方法：应用计算机应用计算机检索PubMed数据库及西文生物医学期刊文献数据库(EMCC)2000-01/2010-10 期间的相关文章,检索词为“Intracranial arterial stenosis,stent Implantation”,并限定文章语言种类为English。同时计算机检索中国期刊全文数据库(CNKI)等2000-01/2010-10期间的相关文章,检索词为“颅内动脉狭窄,支架置入”,并限定文章语言种类为中文。此外还手工查阅相关专著数部。纳入不同材料支架置入治疗颅内动脉狭窄的研究,包括基础研究、临床应用、并发症及材料的生物相容性评定。初检得到151篇文献,根据纳入标准选择33篇文章进行分析。 结果与结论：颅内动脉狭窄的支架置入治疗较单纯药物治疗有明显的优势。近年来,随着冠脉支架及Wingspan支架的运用,支架治疗颅内动脉狭窄已成为一种安全有效的方法。虽然支架置入治疗后会发生不同并发症如再狭窄、脑出血高灌注综合征、缺血性脑卒中等,但支架治疗颅内动脉狭窄在短期及中期有很好的疗效,同时远期疗效还有待进一步研究。提示,支架置入治疗颅内动脉狭窄是一种安全的方法,短、中期内有效,但远期疗效有待进一步研究。药物涂层支架和Wingspan 支架与人体的生物相容性并没有显著差异,尚待进一步论证。     

血管支架对颅内动脉瘤血液动力学的数值模拟

血管支架作为治疗颅内动脉瘤的新方法被广泛运用到临床中,而且越来越普遍。但由于某些支架植入后不能满足力学要求或对瘤内血液动力学无明显影响,反而更易形成血栓,造成动脉瘤破裂。本研究首先通过结构静力学分析比较矩形截面网格状支架和网丝编织成的圆形截面螺旋形支架的弯曲变形能力及扭转变形能力;然后将网格支架植入实际脑动脉瘤模型,进行流－固耦合模拟仿真,分析血流速度、壁面压力及壁面剪切力变化。结果表明：两种支架能够在不损失径向支撑力的情况下,提供良好的轴向顺应性,且网格状支架的变形能力高于螺旋状支架;支架植入后血液动力学各项指标明显降低。血管支架对颅内动脉瘤血液动力学有很大影响,可为临床治疗动脉瘤提供理论依据。     

支架介入治疗颈内动脉狭窄和动脉瘤对动脉瘤壁面压力的影响

目的研究当狭窄与动脉瘤毗邻时,使用支架介入治疗后对动脉瘤壁面压力产生的影响。方法使用计算流体动力学分析的方法对动脉瘤模型及狭窄和动脉瘤毗邻的模型进行对比研究。构建3个模型(M1、M2、M3)对压力变化进行分析比较。M1是颈内动脉瘤模型(无狭窄、无支架),在M1中的动脉瘤前构造一段狭窄动脉形成M2,在M2的动脉瘤部位植入支架后形成M3。结果 M2、M1两个模型相比较,轻度狭窄(50%)引起的动脉瘤部位的压力增加约为1.369 9 kPa(10.3 mmHg)(收缩期的峰值时刻),一个心动周期内动脉瘤部位的平均压力增加约为0.572 kPa(4.3 mmHg)。M3、M2两个模型相比较,动脉瘤部位的压力增加大约为1.037 kPa(7.8 mmHg)(收缩期的峰值时刻),一个心动周期内动脉瘤部位的平均压力增加大约为0.399 kPa(3 mmHg)。结论当使用支架治疗狭窄与弯曲颅内动脉瘤毗邻的患者时,轻度狭窄不会导致显著压力增加。载瘤动脉的形状、动脉瘤或动脉狭窄疾病确实对动脉瘤部位压力变化有影响。     

颅内自膨式支架Enterprise治疗缺血性脑卒中颈内动脉狭窄的远期效果：随机对照临床试验方案

BACKGROUND: The Enterprise stent system is a closed-loop, recoverable self-expanding stent that is effective in the treatment of intracranial aneurysm. However, most studies on the treatment of intracranial aneurysm after ischemic stroke are case series or case reports. OBJECTIVE: To assess the efficacy of the Enterprise stent system for the treatment of carotid artery stenosis in patients with atherosclerotic ischemic stroke. METHODS: We will perform a single-center, double-blind, randomized parallel-controlled trial at the Department of Neurology, Beijing Chao-yang Hospital, Capital Medical University, China. A cohort of 100 patients with atherosclerotic ischemic stroke will be included after obtaining written informed consent from participants or their guardians, and then randomly allocated to undergo either Enterprise self-expanding intracranial stent implantation in combination with antiplatelet medication (stent implantation group, n= 50) or only antiplatelet medication (drug group, n= 50) for treatment of carotid artery stenosis. Four time points (0.5, 1, 2, and 3 years after stent implantation or antiplatelet medication) will be selected for outcome observation and evaluation. The primary outcome will be the National Institutes of Health Stroke Scale score, which is used to evaluate neurologic deficits. The secondary outcomes will be the Barthel index and carotid stenosis rate. The study protocol has been approved by the Ethics Committee of Beijing Chao-yang Hospital, Captical Medical University, China (approval number: GJCY16012) and will be performed in accordance with the guidelines of the Declaration of Helsinki, formulated by the World Medical Association. This trial was registered at ClinicalTrial.gov (NCT02802072). DISCUSSION: There is a lack of randomized controlled studies addressing the long-term effects of the Enterprise self-expanding intracranial stent system for carotid artery stenosis in patients with ischemic stroke. This study will investigate and further confirm the clinical significance of the Enterprise stent system in the treatment of carotid artery stenosis in patients with ischemic stroke.     

血流导向装置在颅内复杂动脉瘤介入治疗中的应用

目的:探讨血流导向装置(FD)在颅内复杂动脉瘤介入治疗中的应用价值。方法:回顾性研究。纳入北京大学国际医院2016年3月—2020年5月采用FD治疗的颅内复杂动脉瘤患者89例,其中男34例、女55例,年龄28～75岁(平均53.08岁)。患者术前均行数字减影血管造影(DSA)检查确诊为颅内复杂动脉瘤,其中大型或巨大动脉...     

Wingspan Stenting for Symptomatic Severe In-Stent Stenosis of a Closed-Cell Stent after Stent-Assisted Coiling of a Ruptured Intracranial Aneurysm

We report the 3-year follow-up result of Wingspan intracranial stenting for symptomatic severe in-stent stenosis after stent-assisted coiling (SAC) for a ruptured left distal internal carotid artery (ICA) aneurysm. A middle-aged male patient visited our hospital for in-stent stenosis of a stent that was placed to treat a ruptured ICA aneurysm. Routine follow-up cerebral angiography, 1 year after SAC, showed in-stent stenosis around the distal markers of the inserted stent at the left M1 proximal segment. Six months later, he developed right dysesthesia. We performed intracranial stenting with Wingspan stent for the in-stent stenosis. Follow-up digital subtraction angiography performed 1 year after the Wingspan stenting showed good patency of the ICA and middle cerebral artery flow without evidence of restenosis. At 3-year follow-up, magnetic resonance angiography showed sufficient middle cerebral artery flow although the stenting segment could not be visualized clearly. Wingspan stenting might be a feasible option in patients with iatrogenic intracranial stenosis resulting from in-stent stenosis who experience the progression of intracranial stenosis with manifestation of neurological symptoms despite dual anti-platelet therapy.     

The efficacy of apolipoprotein E deficiency in cerebral aneurysm formation

Subarachnoid hemorrhage due to the rupture of a cerebral aneurysm is a life-threatening disease. Despite this, the detailed mechanisms underlying the initiation and progression of cerebral aneurysm are unclear. The relation of hypercholesterolemia and apolipoprotein E (ApoE) to cerebral aneurysm formation, has been unclear until now. We used, in the present study, a previously established cerebral aneurysm model of rats and mice whose histological features were closely similar to human cerebral aneurysms. ApoE protein was expressed mainly in the endothelial cells of arterial walls both in control arteries and cerebral aneurysms. The expression of ApoE was reduced during aneurysm formation in the immunohistochemistry. The mRNA expression of ApoE in arterial walls was not different between the controls and cerebral aneurysms. Owing to the deficiency of ApoE, mice presented marked hypercholesterolemia, but there was no difference in cerebral aneurysm formation. In the present study, we clarified that ApoE was not responsible for cerebral aneurysm formation.     

Investigation of intracranial aneurysm hemodynamics following flow diverter stent treatment

Flow diverters (FDs) are high density meshed stents designed to reduce blood flow into intra-cranial aneurysms. Though the FD is one of many intracranial aneurysm (IA) treatments, FD implantation may also result in the growth and rupture of residual aneurysms. The purpose of this research is to investigate the effect of FD implantation on IA hemodynamics. Computational fluid dynamics (CFD) was conducted to analyze dynamic and resistance forces after FD deployment. Simulation results for the successful case (patient A) showed that FD flow resistance force was higher than dynamic force. This indicated that the FD provided sufficient resistance to reduce flow into the aneurysm. As a result, flow velocity magnitude at the aneurysm neck was reduced by 95%. On the other hand, the flow velocity magnitude at the aneurysm neck was reduced by about 50% for the unsuccessful case (patient B). The reason was that the flow resistance force at the aneurysm neck section was calculated to be lower than the flow driving force. In order to completely occlude the aneurysm, a higher resistance FD stent is to be required to suppress the dynamic forces. Patient-specific hemodynamic simulations offer means of quantitative estimation FD treatment outcomes.     

覆膜支架在颅颈血管病变治疗中的应用

背景：随着微导管技术的不断完善和栓塞材料的改进,血管内介入治疗已成为治疗颅颈血管病变的首选方法,主要包括可脱球囊、弹簧圈、液体栓塞剂、覆膜支架。与其他血管内栓塞治疗技术相比,覆膜支架有2个突出优点：有较高的完全闭塞率和较低的再通率。 目的：介绍国内主要应用的几种覆膜支架,以及覆膜支架治疗颅颈动脉瘤和颈内动脉海绵窦瘘的临床效果。 方法：以“覆膜支架,生物相容性,动脉瘤,颈动脉海绵窦瘘”为关键词,采用计算机检索万方数据网1998-01/2010-12相关文章。纳入覆膜支架治疗颅颈血管病变方面的文献,排除重复研究或Mata分析类文章。 结果与结论：现在神经外科临床应用的覆膜支架,主要采用的是美国Abbott公司推出的Jostent覆膜支架和上海微创公司生产的Willis覆膜支架。Jostent覆膜支架优点是生物相容性和扩展性较好,其多微孔结构可减少细胞扩散,阻止血小板聚集、炎性细胞移动,从而降低了继发性血栓及血管狭窄的概率;其缺点是在颅内动脉中应用的范围比较狭窄,动脉不能过于迂曲,弯曲角度不能过于锐利,病变附近不能有不可闭塞的穿支或分支。专为颅内血管设计的Willis覆膜支架的应用,彻底改变了颅内动脉瘤血管内治疗的传统理念,整个支架系统具有一定的柔顺性,有助于其通过颅内弯曲的血管系统,尤其是颈内动脉虹吸段,由于其操作简单,效果满意,为血管内治疗技术的发展提供了新的方向。     

LVIS支架在辅助弹簧圈栓塞颅内宽颈动脉瘤的应用分析

目的 通过分析LVIS支架在辅助弹簧圈栓塞颅内宽颈动脉瘤的临床病例,探讨其有效性及安全性。方法 收集本院神经外科2014年9月~2015年9月应用LVIS支架栓塞颅内宽颈动脉瘤22例,根据Raymond分级评价术中动脉瘤填塞程度,再根据格拉斯哥预后评分评估其疗效。结果 22例宽颈动脉瘤患者均成功施行LVIS支架辅助介入栓塞术,术后即刻Raymond Ⅰ级栓塞,有效栓塞率为100.00%。缺血并发症2例（9.10%）,随访6~24个月,预后良好组有19例（86.40%）。结论 应用LVIS支架在辅助弹簧圈栓塞颅内宽颈动脉瘤是安全有效的,短期随访效果佳,长期疗效有待进一步随访。术后出血并发症未见增加,术中、术后缺血发生率相应增加,与支架金属覆盖率高、展开位置不理想、贴壁不良有关。     

Fabrication of endothelial progenitor cell (EPC)-seeded intravascular stent devices and in vitro endothelialization on hybrid vascular tissue

Rapid re-endothelialization at an atherosclerotic lesion after balloon inflation or stent deployment may be essential for reducing or preventing local thrombus formation and restenosis. In order to prevent these complications via enhanced rapid re-endothelialization, we fabricated two types of endothelial progenitor cell (EPC)-seeded intravascular stent devices. One was a photocured gelatin-coated metallic stent, and the other was a microporous thin segmented polyurethane (SPU) film-covered stent on which photocured gelatin was coated. Both devices were seeded with ex vivo expanded EPCs obtained from canine peripheral blood. Seeded EPCs formed confluent monolayers onto surfaces of both photocured gelatin-coated stent struts and SPU film, and a majority of cells remained on surfaces of stents after stent expansion. The EPC-seeded stent was expanded in a tubular hybrid vascular medial tissue composed of vascular smooth muscle cells and collagen as an arterial media mimic. After 7-day culture, EPCs, which migrated from the stent struts, proliferated and endothelialized the luminal surfaces of the hybrid vascular medial tissue. This in vitro pilot study prior to in vivo experiments suggests that on-stent cell delivery of EPCs may be novel therapeutic devices for re-endothelialization or endothelium lining or paving at an atherosclerotic arterial wall, resulting in the prevention of on-stent thrombus formation and in-stent restenosis, as well as the rapid formation of normal tissue architecture.     

Solitaire支架在颅内宽颈动脉瘤血管内治疗中的应用

目的：探讨应用Solitaire支架结合弹簧圈治疗颅内宽颈动脉瘤的安全性与有效性。方法：回顾性分析Solitaire支架结合弹簧圈治疗的8例颅内宽颈动脉瘤患者的临床资料。结果：本组8例,所有患者术中支架均顺利到位,放置满意,术中无操作相关并发症发生。术后获随访6。24个月（平均12．9个月）,随访期间患者无一例死亡,无再出血及栓塞等症状。术后6个月按GOS评分评定远期生活质量,患者恢复良好率或轻残率为87．5％（7／8）。术后1a复查血管造影结果显示,所有患者载瘤动脉及毗邻的血管均保持通畅,无支架或弹簧圈移位发生;7例患者动脉瘤完全闭塞;1例患者动脉瘤残留或复发。影像学治愈率87．5％（7／8）。结论：血管内Solitaire支架植入结合弹簧圈治疗颅内宽颈动脉瘤是一种安全、有效的治疗手段。     

Histological analysis of clipped human intracranial aneurysms and parent arteries with short-term follow-up

BackgroundSurgical clipping of intracranial aneurysms is the gold standard for the prevention of rupture. However, the biological processes that occur following clipping are poorly understood. To better understand these effects, retrieved and clipped human intracranial aneurysms were examined histologically.MethodsAt autopsy, 17 aneurysms from 10 patients were retrieved 3–21 days after clipping. The tissues were embedded in paraffin, and microtome sections were stained using hematoxylin–eosin and Movat pentachrome. Using light microscopy, clip placement relative to the internal elastic lamina of the parent artery, endothelialization of the aneurysm neck, thrombus organization inside the aneurysm sac, inflammation in the sac, wall, and parent artery, and atherosclerotic changes were determined.ResultsDespite complete reconstruction of the artery with the clip, diseased vessel wall was frequently observed outside the clip. By 10 days postsurgery, the beginnings of endothelialization and neointima formation were observed at the neck. However, the neck coverage was variable and incomplete at these early time points. Thrombus organization inside the aneurysm sac was rarely observed, and inflammatory cells were not present inside the aneurysm sac. Inflammatory cells were commonly observed in the aneurysm wall, and atherosclerotic change was present in each sample.ConclusionsComplete aneurysm exclusion and apposition of healthy arterial wall occurred infrequently in our series. Endothelialization and neointima formation at the aneurysm neck take some time to complete and are often incomplete. The effectiveness of aneurysm clipping is related to the mechanics of aneurysm exclusion rather than the processes of endothelialization and neointima formation.SummaryComplete aneurysm exclusion and apposition of healthy arterial wall occurred infrequently in our series. Endothelialization and neointima formation at the aneurysm neck take some time to complete and are often incomplete. The effectiveness of aneurysm clipping is related to the mechanics of aneurysm exclusion rather than the processes of endothelialization and neointima formation.     

Development of nanofiber-covered stents using electrospinning: in vitro and acute phase in vivo experiments

There are some technical difficulties in treating for a broad necked aneurysm and a higher incidence of recurrence. Because of these drawbacks, more innovative techniques for superior endovascular reconstructive treatment are required. We developed a novel covered stent employing electrospinning to deposit fine polyurethane (PU) fibers onto stents. An in vitro water leak test was designed and applied prior to animal testing to estimate the performance of covered stents and to determine the appropriate amount of PU fibers on a stent. Two tenths of a milligram of PU fibers proved to be sufficient to prevent water leakage. Then, the efficacy of the covered stents to that of bare stents was compared using 10 rabbits in which model aneurysms had been formed at the right common carotid artery by the elastase method. Angiographic evaluation on day 1 posttreatment (acute phase) revealed complete occlusion of the aneurysms and the patency of the parent arteries in animals treated with covered stents. At 10 days poststenting (subacute phase), the aneurysm neck was completely covered with neointimal layer as shown by scanning electron microscopic examination. The PU-covered stent holds promise as a device for treating cerebral aneurysms.     

Segmental arterial mediolysis: course,sequelae, prognosis,and pathologic–radiologic correlation

BackgroundSegmental arterial mediolysis is a vascular disease of putative vasospastic origin that causes massive hemorrhages. Although once considered rare, awareness of this disease has resulted in increased reports in the pathology and radiology literature. Despite this, uncertainties concerning pathologic and radiologic correlations, the course of this disease, and aspects of its prognosis exist. This article addresses these issues.MethodsThirteen radiologic reports of segmental arterial mediolysis are analyzed, and slides of 25 cases of segmental arterial mediolysis are searched for lesions analogous to the radiologic findings.ResultsSix angiographic presentations are identified: (a) arterial dilatation, (b) single aneurysm, (c) multiple aneurysms, (d) dissecting hematomas, (e) arterial stenosis, and (f) arterial occlusions. Pathologic correlations reveal that lytic loss of medial muscle causes arterial dilatation, dilated arterial gaps form aneurysms, dissections develop at arterial–medial gap junctions or from reparative granulation tissue and reparative alterations, and thrombi cause stenosis and occlusions. The most common radiologic findings at onset are aneurysms, arterial dilatation, and occlusions, while dissections and stenotic lesions often are delayed. These images correlate with the histologic evolution of segmental arterial mediolysis.ConclusionsSegmental arterial mediolysis is an acute limited disease. Sequelae recognized radiologically include aneurysms, dissecting hematomas, arterial stenosis, and occlusions. Generally, these persist, become smaller, or resolve, but symptomatic dissections with delayed onset occur. Sequelae of subclinical forms of segmental arterial mediolysis may cause isolated idiopathic aneurysms or may evolve into arterial lesions indistinguishable from fibromuscular dysplasia.