大蒜素包被支架术后冠状动脉管壁原癌基因c-fos表达的变化

目的：探讨大蒜素（DT）包被支架置入后对血管内膜增生及管壁原癌基因c-fos表达的影响。方法：直接支架置入术建立犬冠状动脉内膜损伤模型，观察血管形态学变化，并用RT-PCR方法检测不同时点冠状动脉壁内c-fos基因的表达丰度。结果：单纯蛋白包被支架置入后4周管壁内膜明显增生，DT包被支架明显抑制内膜增生。对照组c-fos基因在术后1 d有大量的表达，7 d达高峰，以后随时间的推移表达逐渐下降,28 d仍可检出。与对照组相比，各时点DT包被支架均显著抑制c-fos mRNA的表达。结论：DT包被支架具有抑制c-fos基因的表达与内膜增生的作用。     

Suppression of post-angioplasty restenosis with an Akt1 siRNA-embedded coronary stent in a rabbit model

Restenosis is the formation of blockages occurring at the site of angioplasty or stent placement. In order to avoid such blockages, the suppression of smooth muscle cells near the implanted stent is required. The Akt1 protein is known to be responsible for cellular proliferation, and specific inhibition of Akt1 gene expression results in the retardation of cell growth. To take advantage of these benefits, we developed a new delivery technique for Akt1 siRNA nanoparticles from a hyaluronic acid (HA)-coated stent surface. For this purpose, the disulfide cross-linked low molecular polyethyleneimine (PEI) (ssPEI) was used as a gene delivery carrier because disulfide bonds are stable in an oxidative extracellular environment but degrade rapidly in reductive intracellular environments. In this study, Akt1 siRNA showed efficient ionic interaction with the ssPEI carrier, which was confirmed by polyacrylamide gel electrophoresis. Akt1 siRNA/ssPEI nanoparticles (ASNs) were immobilized on the HA-coated stent surface and exhibited stable binding and localization, followed by time-dependent sustained release for intracellular uptake. Cellular viability on the nanoparticle-immobilized surface was assessed using A10 vascular smooth muscle cells, and the results revealed that immobilized ASNs exhibited negligible cytotoxicity against the adhering A10 cells. Transfection efficiency was quantified using a luciferase assay; the transgene expression of Akt1 suppression through the delivered Akt1 siRNA was measured using RT-PCR and western blot, demonstrating higher gene silencing efficiency when compared to other carriers. ASN coated on HA stents were deployed in the balloon-injured external iliac artery in rabbits in?vivo. It was shown that the Akt1 released from the stent suppressed the growth of the smooth muscle at the peri-stent implantation area, resulting in the prevention of restenosis in the post-implantation phase.     

新型生物全降解药物支架置入小型猪冠状动脉的安全性

背景：目前冠状动脉支架的主要研究方向是高生物相容性的全降解生物材料及药物控释体系。 目的：评价2种新型生物全降解药物支架置入小型猪冠状动脉后的安全性。 方法：普通生物全降解支架为在聚左旋乳酸本体中融入抗增殖药物紫杉醇,新型生物全降解支架为在聚左旋乳酸及紫杉醇的基础上融入一种新型纳米材料无定形磷酸钙。①将普通生物全降解支架和新型生物全降解支架各5枚在冠状动脉造影下分别随机置入小型猪的冠状动脉,每种支架5头。于置入前和置入后28 d行血生化及C-反应蛋白水平检测;术后28 d冠状动脉造影观察支架置入段管腔通畅情况。②在微创显微镜辅助下于兔右髂外动脉分别置入普通生物全降解支架和新型生物全降解支架管状半成品(材料成分与上述支架一致),每种支架7只,在术前和术后28 d检测血尿素氮及肌酐水平。 结果与结论：置入后28 d两组猪谷丙转氨酶、谷草转氨酶、三酰甘油、总胆固醇、低密度脂蛋白及C-反应蛋白水平与置入前相比均无明显变化,但尿素氮、肌酐水平均明显高于置入前(P < 0.05);两组支架置入段血管均血流通畅、无血栓迹象和狭窄形成。支架置入前后两组兔肌酐和尿素氮水平无明显变化。表明新型生物全降解药物支架置入健康小型猪冠状动脉后是相对安全的,并且支架具有良好的组织相容性。     

Simulation of longitudinal stent deformation in a patient-specific coronary artery

In percutaneous coronary intervention (PCI), stent malapposition is a common complication often leading to stent thrombosis (ST). More recently, it has also been associated with longitudinal stent deformation (LSD) normally occurring through contact of a post balloon catheter tip and the protruding malapposed stent struts.The aim of this study was to assess the longitudinal integrity of first and second generation drug eluting stents in a patient specific coronary artery segment and to compare the range of variation of applied loads with those reported elsewhere. We successfully validated computational models of three drug-eluting stent designs when assessed for longitudinal deformation. We then reconstructed a patient specific stenosed right coronary artery segment by fusing angiographic and intravascular ultrasound (IVUS) images from a real case. Within this model the mechanical behaviour of the same stents along with a modified device was compared. Specifically, after the deployment of each device, a compressive point load of 0.3 N was applied on the most malapposed strut proximally to the models. Results indicate that predicted stent longitudinal strength (i) is significantly different between the stent platforms in a manner consistent with physical testing in a laboratory environment, (ii) shows a smaller range of variation for simulations of in vivo performance relative to models of in vitro experiments, and (iii) the modified stent design demonstrated considerably higher longitudinal integrity. Interestingly, stent longitudinal stability may differ drastically after a localised in vivo force compared to a distributed in vitro force.     

樟芝三萜类化合物的抗炎作用

<正>炎症是许多病理状态中机体对有害刺激的应答。例如,一些肿瘤在发生前或发生时常有慢性炎症。据报道,慢性炎症与1/4以上的肿瘤发生相关,相当于全世界每年约320多万人罹患炎症相关的肿瘤[1]。如石棉吸入与间皮瘤,二氧化硅吸入、吸烟、支气管哮喘与支气管癌,宫颈炎、HPV感染与宫颈癌,盆腔炎及卵巢上皮炎症与卵巢癌,EB病毒感染与鼻咽癌,HIV感染与卡西波肉瘤,返流性食管炎与食管癌,幽门螺旋杆菌感染相关性胃炎与胃癌,慢性     

Short-, mid-, and long-term effects of a polymer-free tacrolimus-eluting stent in a porcine coronary model

Stent-based delivery of tacrolimus has shown neointimal hyperplasia and restenosis reduction; FK506 is a water insoluble macrolide immunosuppressant. The purpose of this study was to evaluate acute and chronic tissue response to a polymer-free FK506 drug-eluting stent implantation in a porcine coronary artery model. Seventy-eight nonatherosclerotic minipigs underwent successful placement of 134 stents (control n = 56; FK506 (1.5 microg/mm(2)) n = 44; FK506 (2.6 microg/mm(2)) n = 34) at 7, 15, 30, 90, or 180 days. Endothelialisation was almost complete at 7 days, complete at 15 days. At 30 and 90 days, mean neointimal thickness, neointimal area, and % stenosis was significantly less for drug-eluting stents compared with controls. At 180 days, histomorphometric values were similar for eluting and control stents. The FK506-eluting stent allows for a complete re-endothelialisation at 15 days and favorably moderate neointimal hyperplasia at 30 and 90 days in the porcine coronary model. Because of a possible limited bioavailability of FK506, long-term inhibition of neointimal formation was not sustained at the considered follow-up.     

New stent surface materials: The impact of polymer-dependent interactions of human endothelial cells,smooth muscle cells,and platelets

Despite the development of new coronary stent technologies, in-stent restenosis and stent thrombosis are still clinically relevant. Interactions of blood and tissue cells with the implanted material may represent an important cause of these side effects. We hypothesize material-dependent interaction of blood and tissue cells. The aim of this study is accordingly to investigate the impact of vascular endothelial cells, smooth muscle cells and platelets with various biodegradable polymers to identify a stent coating or platform material that demonstrates excellent endothelial-cell-supportive and non-thrombogenic properties. Human umbilical venous endothelial cells, human coronary arterial endothelial cells and human coronary arterial smooth muscle cells were cultivated on the surfaces of two established biostable polymers used for drug-eluting stents, namely poly(ethylene-co-vinylacetate) (PEVA) and poly(butyl methacrylate) (PBMA). We compared these polymers to new biodegradable polyesters poly(l-lactide) (PLLA), poly(3-hydroxybutyrate) (P(3HB)), poly(4-hydroxybutyrate) (P(4HB)) and a polymeric blend of PLLA/P(4HB) in a ratio of 78/22% (w/w). Biocompatibility tests were performed under static and dynamic conditions. Measurement of cell proliferation, viability, glycocalix width, eNOS and PECAM-1 mRNA expression revealed strong material dependency among the six polymer samples investigated. Only the polymeric blend of PLLA/P(4HB) achieved excellent endothelial markers of biocompatibility. Data show that PLLA and P(4HB) tend to a more thrombotic response, whereas the polymer blend is characterized by a lower thrombotic potential. These data demonstrate material-dependent endothelialization, smooth muscle cell growth and thrombogenicity. Although polymers such as PEVA and PBMA are already commonly used for vascular implants, they did not sufficiently meet the criteria for biocompatibility. The investigated biodegradable polymeric blend PLLA/P(4HB) evidently represents a promising material for vascular stents and stent coatings.     

In vitro investigations with a new method for continuous and quantitative measurements of platelet aggregates in flowing blood

Summary Heparinized dog's blood in vitro is sucked at a constant rate by a syringe pump through a glass capillary which lies in the axial stream of a perfused plexiglass chamber. The capillary is projected with a microscope onto a screen at a magnification of 175x. Changes of light intensity due to the streaming blood are monitored by two photocells covering the diameter of the image of the capillary. Because of their higher transparency platelet aggregates are differing from the surrounding suspension of red blood cells. The photocells thereby produce voltage peaks of high amplitude which after their transformation into standardized signals can be counted electronically. By the use of this technique the kinetics of platelet aggregation can be followed continuously. In addition, a correlation between platelet count in the blood and the number of aggregates counted after ADP can be demonstrated.Partially presented at the 37. Tagung der Deutschen Physiologischen Gesellschaft, Erlangen 1970.     

冠状动脉支架置入患者血清炎症因子表达及血管再狭窄

目的：评价冠状动脉支架置入后血清炎症因子对再狭窄形成的影响。 方法：以“冠状动脉疾病,冠状动脉支架置入,炎症介导,支架材料”为检索词,检索中国期刊文数据库及Medline数据库2001/2010相关文献。纳入研究对象为冠状动脉粥样硬化性心脏病需要支架置入治疗的患者;经冠状动脉造影检查证实为冠心病的患者;不限定患者的年龄、性别、种族及地域,且同意行冠状动脉支架置入治疗;检测指标为炎症因子表达。排除感染性疾病、出血性疾病、白血病、严重肝病、严重肾功能不全及肿瘤者。重点对23条文献进行探讨。 结果：支架置入后随着血清可溶性细胞间黏附分子1浓度增加sCD40L浓度也增加。支架置入后血清可溶性细胞间黏附分子1、基质金属蛋白酶9浓度均明显升高,并上调了黏附因子血清可溶性细胞间黏附分子1、基质金属蛋白酶9的表达;对血清白细胞介素18及C-反应蛋白的水平有明显影响。 结论：结果说明在支架置入过程中,球囊扩张、支架置入等一系列挤压斑块因素, 促进了炎症因子释放,增加了血清炎症因子的水平。冠脉血管损伤后血管重构及再灌注也是促其增高的原因,而升高幅度与冠脉病变程度密切相关。     

Anti-inflammatory and anti-allergic effects of kefir in a mouse asthma model

Kefir is a microbial symbiont mixture that produces jelly-like grains. As a widely used neutraceutical, however, the therapeutic applicability of kefir is not certain. In order to investigate the pharmacological effects of kefir, we used a mouse asthma model, in which airway inflammation and airway remodeling was produced by ovalbumin sensitization and challenge. BALB/c mice sensitized and challenged to ovalbumin, were treated with kefir (50mg/kg administered by intra-gastric mode) 1h before the ovalbumin challenge. Kefir significantly suppressed ovalbumin-induced airway hyper-responsiveness (AHR) to inhaled methacholine. Intra-gastric administration of kefir significantly inhibited the increase in the total inflammatory cell count induced by ovalbumin, and the eosinophil count in bronchoalveolar lavage fluid (BALF). Type 2 helper T cell (Th2) cytokines, such as interleukin-4 and interleukin-13, and total immunoglobulin E (Ig E) levels, were also reduced to normal levels in bronchoalveolar lavage fluid. Histological studies demonstrate that kefir substantially inhibited ovalbumin-induced eosinophilia in lung tissue and mucus hyper-secretion by goblet cells in the airway. Kefir displayed anti-inflammatory and anti-allergic effects in a mouse asthma model and may possess new therapeutic potential for the treatment of allergic bronchial asthma.     

Very late stent thrombosis after drug-eluting stent implantation in a patient without aspirin and clopidogrel resistance

Very late stent thrombosis (VLST) after implantation of drug-eluting stent is rare, but very fatal complication after percutaneous coronary intervention. We report a case of VLST of a sirolimus-eluting Cypher stent (Cordis, Johnson and Johnson) presenting as acute ST elevation myocardial infarction at 26 months after deployment with continued combined dual antiplatelet medication of aspirin and clopidogrel. The patient did not show anti-platelet resistance.     

支架置入前脑动脉瘤血流场的特性分析

BACKGROUND: Cerebral aneurysm is a kind of mortal hemangioma, and its treatments such as endovascular embolization and clipping both cause high postoperative recurrence rate and mortality. So the stent implantation for cerebral aneurysm is coming into being. OBJECTTVE: To evaluate the hemodynamic parameters after stent implantation into cerebral aneurysm and to provide a novel feasible strategy for clinical treatment. METHODS: A retrospective analysis was preformed based on the CT image data of 11 patients with cerebral aneurysm from the Affiliated Hospital of Xinjiang Medical University. Firstly, the flexible and solid model of cerebral aneurysm was established by the MIMICS and reverse engineering. Secondly, the matching stent model was implanted into the cerebral aneurysm, and then the blood flow structure of cerebral aneurysm was analyzed by the fluid dynamics theory and the Fluent with the method of two-way flow solid coupling. Finally, comparative analysis of the kinetic parameters of cerebral aneurysm before and after implantation, including wall pressure, blood velocity, path line of the blood flow, wall shear stress, wall deformation was conducted, and blood flow characteristics after stent implantation were analyzed under different entrance velocity. RESULTS AND CONCLUSION: After implantation, the wall surface pressure was reduced about 61.1%; the blood flow velocity around the stent and the inside of the cerebral aneurysm was decelerated obviously; under setting 2 000 lines of blood flow, the number of path line of blood flow into the cerebral aneurysm reduced about 75.0%, the maximum wall shear stress decreased about 79.3%, and the maximum wall deformation reduced to a lower level. The entrance velocity was respectively v1=0.1 m/s, v2=0.2 m/s, v3=0.3 m/s and the wall pressure was in a gradient ascent; the wall shear stress increased with the velocity, meanwhile, τzou (left neck of aneurysm) <τzhong (aneurysm )< τyou (right neck of aneurysm). The path lines of blood flow mainly concentrated in the top of the aneurysm, and the blood velocity markedly affected the surface deformation. These results indicate that main hemodynamic parameters are obviously improved after stent implantation into cerebral aneurysm, and the blood velocity should never be neglectful in the treatment process.     

血流作用下冠脉支架的疲劳寿命优化

目的评估血流作用下冠脉支架的疲劳寿命,并在此基础上对支架的疲劳寿命进行优化设计。方法采用Pro/Engineer建立包含植入支架、血液、血栓以及动脉壁的简化组合模型,使用ANSYS有限元分析程序,利用有限元法模拟支架在动脉壁中受血流的周期性作用,并根据支架内的血流动力学分析结果对评估支架的疲劳寿命。以支架的几何参数作为设计变量,通过拉丁超立方抽样方法选取样本点并得到对应的响应值,建立Kriging代理模型,对冠脉支架的疲劳寿命进行优化。结果 Goodman图显示优化后支架是安全的;累积损伤法表明支架最大损伤点处于支架血流流入端的第2交叉面上,优化后支架的疲劳寿命提高30.55%。结论有限元法可对冠脉支架疲劳寿命进行有效的评估,建立Kriging代理模型对支架进行优化设计可以有效地提高支架的使用寿命。     

Local delivery of nitric oxide from an eluting stent to inhibit neointimal thickening in a porcine coronary injury model

To assess the effect of a NO-eluting stent on reducing neointimal thickening in a porcine coronary artery stent injury model, sodium nitroprusside (SNP), a NO donor, was incorporated into polyurethane (PU) polymer and coated onto metallic coil stents, and two types of stents with thin and thick barrier coatings were characterized. In vivo biological activity of the NO-eluting stents was assessed by measurement of coronary arterial cGMP levels in 32 pigs/64 arteries at days 1, 2, 7 and 14. Morphometric analyses were performed in 16 pigs to determine the effect of NO-eluting stents on neointimal hyperplasia 28 days following arterial injury. The SNP-coated stents released NO in a controlled manner for up to 4 weeks in the in vitro experiments and an increase in local tissue cGMP levels was demonstrated for up to 14 days. The neointimal area at 28 days was not diminished, however, by NO eluded from either stents of thin or thick barriers (control bare stent - 0.66 mm2, control PU stent - 0.68 mm2, SNP-PU thin coating stent - 0.78 mm2, SNP-PU thick coating stent - 0.85 mm2; all p=NS). In conclusion, the SNP-coated polymer stent exerted a local biological effect on the arterial wall, with sustained elevation of cGMP level. Although local delivery of NO from this device did not reduce neointimal hyperplasia in this porcine model, this polymer-coated stent might be a promising tool for administration of other agents that may modify the reparative tissue responses leading to restenosis.     

X-ray micro-tomography of a coronary stent deployed in a model artery

Coronary stents are small scaffolds routinely implanted during angioplasty procedures to re-open coronary arteries which have become narrowed by an atherosclerotic plaque. Despite the advent of drug-eluting stents to reduce restenosis (re-narrowing) after the procedure, complications still arise and mechanical factors may be partly the cause. Stents are being used in increasingly complex cases, so new forms of pre-clinical testing may be helpful in evaluating stent designs and deployment techniques. With this in mind, an in vitro experiment was conducted to evaluate the use of X-ray micro-tomography to image stents at various stages of deployment. A stent was deployed in an artificial artery while using a synchrotron X-ray source to obtain the tomography scans. A volume element (voxel) size of 5.3 μm was achieved, with a vertical field of view of 4.5 mm. The imaging of the stent and artificial artery materials was better than expected, despite some attenuation artifacts and the high monochromatic beam energy used (25 keV). Experimental problems are discussed, together with recommendations for improving the technique. It is intended that this technique will be of interest to engineers and clinicians as a pre-clinical test.     

Polymerized degradable hyaluronan--a platform for stent coating with inherent inhibitory effects on neointimal formation in a porcine coronary model

Biodegradable hyaluronan (hyaluronic acid, HA) made insoluble by self-cross-linking in the presence of N-(3-dimethylaminopropyl)-N'-ethyl carbodiimide (EDC) has been used to cover stents. The maximum polymer-mass on a 16-mm stainless steel stent is approximately 2 mg. During manual crimping and simulated application, the loss of polymerized HA is negligible. The insoluble HA coating has an advantageous inherent antiproliferative effect regarding neointimal formation after local vessel wall injury (overstretch model) and leads to a reduced inflammatory response compared to uncoated stainless-steel stents, used as control, in undiseased pig coronary arteries, over a follow-up period of four weeks. Thus, cross-linked HA stent coating warrants further research as an interactive degradable biomaterial with an inherent inhibitory effect on neointimal formation as a possible biomatrix for local drug delivery to reduce restenosis rate.     

Platelet transfusion in adults: An update

Many patients worldwide receive platelet components (PCs) through the transfusion of diverse types of blood components. PC transfusions are essential for the treatment of central thrombocytopenia of diverse causes, and such treatment is beneficial in patients at risk of severe bleeding. PC transfusions account for almost 10% of all the blood components supplied by blood services, but they are associated with about 3.25 times as many severe reactions (attributable to transfusion) than red blood cell transfusions after stringent in-process leukoreduction to less than 10⁶ residual cells per blood component. PCs are not homogeneous, due to the considerable differences between donors. Furthermore, the modes of PC collection and preparation, the safety precautions taken to limit either the most common (allergic-type reactions and febrile non-hemolytic reactions) or the most severe (bacterial contamination, pulmonary lesions) adverse reactions, and storage and conservation methods can all result in so-called PC “storage lesions”. Some storage lesions affect PC quality, with implications for patient outcome. Good transfusion practices should result in higher levels of platelet recovery and efficacy, and lower complication rates. These practices include a matching of tissue ABH antigens whenever possible, and of platelet HLA (and, to a lesser extent, HPA) antigens in immunization situations. This review provides an overview of all the available information relating to platelet transfusion, from donor and donation to bedside transfusion, and considers the impact of the measures applied to increase transfusion efficacy while improving safety and preventing transfusion inefficacy and refractoriness. It also considers alternatives to platelet component (PC) transfusion.     

G蛋白β3亚单位基因C825T多态性与PTCA支架内再狭窄

目的 探讨G蛋白β3亚单位基因C825T多态性与PTCA支架植入后再狭窄之间的相关性。方法 采用多聚酶联反应结合限制性内切酶片断长度多态性分析方法(PCR-RFLP)检测50例经PTCA支架植入术后半年内发生再狭窄的患者和85例经PTCA支架植入在半年内未发生再狭窄的患者之间G蛋白β3亚单位基因C825T多态性。结果 再狭窄组G蛋白β3亚单位基因型频率(CC 14％、CT 54％、TT 32％),等位基因频率(C 41％、T 59％)与未狭窄组G蛋白β3亚单位基因型频率(CC31.8％、CT 44.7％、TT 23.5％),等位基因频率(C 54.2％、T 45.8％)比较统计学上有差异。结论 G蛋白β3亚单位基因C825T多态性可能与PTCA支架内再狭窄有关。     

Clinical benefit of low molecular weight heparin for ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with glycoprotein IIb/IIIa inhibitor

The efficacy of low molecular weight heparin (LMWH) with low dose unfractionated heparin (UFH) during percutaneous coronary intervention (PCI) with or without glycoprotein (Gp) IIb/IIIa inhibitor compared to UFH with or without Gp IIb/IIIa inhibitor has not been elucidated. Between October 2005 and July 2007, 2,535 patients with ST elevation acute myocardial infarction (STEMI) undergoing PCI in the Korean Acute Myocardial Infarction Registry (KAMIR) were assigned to either of two groups: a group with Gp IIb/IIIa inhibitor (n=476) or a group without Gp IIb/IIIa inhibitor (n=2,059). These groups were further subdivided according to the use of LMWH with low dose UFH (n=219) or UFH alone (n=257). The primary end points were cardiac death or myocardial infarction during the 30 days after the registration. The primary end point occurred in 4.1% (9/219) of patients managed with LMWH during PCI and Gp IIb/IIIa inhibitor and 10.8% (28/257) of patients managed with UFH and Gp IIb/IIIa inhibitor (odds ratio [OR], 0.290; 95% confidence interval [CI], 0.132-0.634; P=0.006). Thrombolysis In Myocardial Infarction (TIMI) with major bleeding was observed in LMHW and UFH with Gp IIb/IIIa inhibitor (1/219 [0.5%] vs 1/257 [0.4%], P=1.00). For patients with STEMI managed with a primary PCI and Gp IIb/IIIa inhibitor, LMWH is more beneficial than UFH.