静脉桥狭窄家兔动物模型的建立

目的建立冠心病冠状动脉旁路移植术后移植静脉桥狭窄的动物模型。方法取3.0～3.5 kg普通新西兰兔8只,取同侧颈外静脉与颈总动脉进行端端吻合,吻合时采用间断缝合的方法。结果术后2周、4周取下静脉桥及对侧颈外静脉,光镜下见静脉桥新生内膜形成,中膜增厚,弹力纤维减少;胶原纤维不均匀性增厚。结论本模型能反映冠状动脉旁路移植术后静脉桥狭窄的情况,可满意模拟人冠状动脉旁路移植术后大隐静脉桥的病理变化。     

冠状动脉旁路移植术桡动脉桥家兔模型的建立

目的建立一个能模拟冠状动脉旁路移植术桡动脉桥情况的模型。方法50只新西兰兔,股动脉与颈总动脉行端侧吻合,两吻合口之间的颈总动脉予以结扎。术后1、3、7、14、56d分别取完整动脉桥,进行肉眼观察,HE染色观察病理变化,弹力纤维染色,计算机测算血管内膜厚度、新生内膜中膜比指数;电镜观察血管内皮细胞变化。结果50只兔成功建立动脉桥,无手术及围手术期死亡,桥血管总通畅率为86％,对通畅的桥血管作形态学观测发现血管移植后7d起至56d内膜增厚有统计学差异。结论本动物模型可以较好地模拟冠状动脉旁路移植术桡动脉桥的情况。     

兔颈动、静脉移植桥血管狭窄模型的建立及其电镜观察

目的：建立兔颈动、静脉移植血管桥动物模型,观察移植桥血管内膜增生和狭窄的电镜下表现。方法：通过兔双侧颈动脉进行动脉桥和静脉桥的移植,形成双侧移植血管桥再狭窄动物模型。在第8周施行血管桥移植手术的同时留取右侧颈动静脉标本作为对照血管,再分别于第12周、16周和第20周分别处死模型兔,采集移植桥血管标本,在光镜下测量其内膜厚度、面积、狭窄度,并进行电镜观察。结果：颈动脉和颈静脉桥移植后,随着时间的延长,桥血管的出现平滑肌迁移,脂质沉积,内膜增生,血管狭窄等改变,且以静脉桥血管的病理改变更为明显。结论：在兔形成动脉粥样硬化病变基础上,进行双侧颈动脉血管桥的移植,建立兔双侧颈动脉移植血管桥再狭窄动物模型,有利于设立自身对照,研究术后动静脉桥再狭窄差异机制;建立动、静脉桥后,位于血管中膜的平滑肌细胞出现向血管内膜迁移现象,说明中膜平滑肌细胞迁移进入内膜导致新内膜形成是血管再狭窄的重要环节。     

兔颈动、静脉移植桥血管狭窄模型的建立及其电镜观察

目的:建立兔颈动、静脉移植血管桥动物模型,观察移植桥血管内膜增生和狭窄的电镜下表现。方法:通过兔双侧颈动脉进行动脉桥和静脉桥的移植,形成双侧移植血管桥再狭窄动物模型。在第8周施行血管桥移植手术的同时留取右侧颈动静脉标本作为对照血管,再分别于第12周、16周和第20周分别处死模型兔,采集移植桥血管标本,在光镜下测量其内膜厚度、面积、狭窄度,并进行电镜观察。结果:颈动脉和颈静脉桥移植后,随着时间的延长,桥血管的出现平滑肌迁移,脂质沉积,内膜增生,血管狭窄等改变,且以静脉桥血管的病理改变更为明显。结论:在兔形成动脉粥样硬化病变基础上,进行双侧颈动脉血管桥的移植,建立兔双侧颈动脉移植血管桥再狭窄动物模型,有利于设立自身对照,研究术后动静脉桥再狭窄差异机制;建立动、静脉桥后,位于血管中膜的平滑肌细胞出现向血管内膜迁移现象,说明中膜平滑肌细胞迁移进入内膜导致新内膜形成是血管再狭窄的重要环节。     

选择性冠状静脉动脉化搭桥术中不同移植物的应用疗效比较

目的:对比选择性冠状静脉动脉化(SCVBG)搭桥治疗弥漫性右冠状动脉狭窄病变中选择乳内动脉和大隐静脉作为桥血管的治疗效果。方法:选择2008年10月到2014年10月在我院行SCVBG搭桥的84例患者资料,其中选择大隐静脉作为桥血管进行冠状静脉动脉化搭桥患者46例(大隐静脉桥组),选择乳内动脉作为桥血管进行冠状静脉动脉化搭桥患者38例(乳内动脉桥组)。随访记录两组患者的生存情况、近期复查超声心动图、冠状动脉CTA及心绞痛复发率。结果:乳内动脉桥组患者总生存率(100%)明显高于大隐静脉桥组(82.6%)(P0.05)。乳内动脉桥组患者桥血管和心中静脉通畅率(100%)明显大于大隐静脉桥组(54.35%)(P0.05)。两组患者左心室射血分数(LVEF)较治疗前明显增加,左心室舒张期末内径(LVEDD)较治疗前明显减小(P0.05)。治疗后,乳内动脉桥组患者心绞痛复发率明显小于大隐静脉桥组(P0.05)。结论:SCVBG搭桥治疗弥漫性右冠状动脉狭窄病变中,选择乳内动脉桥效果优于大隐静脉桥,能明显提高桥血管和心中静脉通畅率,降低心绞痛复发率。     

大鼠肾移植慢性排斥反应模型的建立

目的建立一种稳定的大鼠原位肾移植慢性排斥反应模型。方法供体为近交系F344大鼠,受体为Lewis大鼠,供肾采用左肾,在体修整,原位灌注。肾静脉用硬膜外导管做为临时内支架管端-端、六针法吻合,腹主动脉端-侧连续缝合,输尿管带膀胱瓣与膀胱吻合。受体术前3 d开始环孢素A灌胃至术后30 d（5 mg/kg·d）,以预防急性排斥反应。结果手术时间120～180 min;手术成功率90.9%（40P44）;受体均存活60 d。并发症有吻合口出血、静脉血栓形成、急性排斥反应等。结论供肾原位灌注,在体修整是简单可靠的方法。静脉內支架管端端吻合,腹主动脉端侧吻合能够达到稳定的成功率,值得推广。熟练的外科操作技能和血管吻合技术是手术成功的关键。     

大鼠心脏移植急性排斥反应动物模型的建立

目的为探索器官移植后急性排斥反应的一种快速可靠的诊断方法。方法先暴露和游离受体的吻合段血管,再获取供心以缩短移植心脏冷缺血时间;保留供者的心脏及右上肺,将其胸主动脉与受者的腹主动脉间断端侧吻合;开放血流时,先开放远心端再间断开放近心端,同时按摩心脏至心脏搏动规律、有力,其色泽恢复红润,右上肺亦充盈良好。结果A组(n=20)成功16只,动脉吻合口出血2只、心脏复跳失败1只、吻合口狭窄1只;B组(n=20)成功17只,2只死于吻合口出血,1只死于吻合口狭窄。A组手术成功率为80%,B组为85%(P>0.05)。结论(1)先暴露并游离好受体血管吻合段,再获取供心,可以缩短移植心冷缺血时间。(2)边灌注边获取的方法利于快速而又完整的获取供心。(3)在切取和植入的过程中一定要注意低温保护。(4)利用腹主动脉段进行移植,使手术方便易行。左心做功的大鼠腹部心脏移植模型简单、安全、实用,因其左心参与循环而使血流动力学更接近生理状态,是进行心脏移植及血流动力学研究的较理想模型。     

间断切口与长切口获取大隐静脉在冠状动脉旁路移植术中作用的对比研究

目的:比较冠状动脉旁路移植术(CABG)中采用间断切口与长切口获取大隐静脉作为静脉桥材料的优缺点。方法:选择2011年12月至2012年12月宁夏医科大学总医院心脏大血管外科111例行CABG的冠状动脉粥样硬化性心脏病患者为研究对象。根据术中获取大隐静脉方法的不同,随机将其分为两组,长切口组64例,在CABG中采用长切口法获取大隐静脉,间断切口组47例,在CABG中采用间断切口法获取大隐静脉。比较两组大隐静脉获取时间、下肢切口缝合时间、下肢手术时间、大隐静脉桥长度、下肢切口长度和下肢切口并发症发生率的差异。结果:间断切口组大隐静脉桥长度及下肢手术时间(45.4±6.7)cm,(65.8±10.3)min与长切口组(47.5±6.7)cm,(65.8±10.3)min比较无统计学差异(P0.05)。间断切口组获取大隐静脉的时间(48.9±8.3)min显著长于长切口组(37.3±5.8)min,下肢切口长度与缝合时间(17.0±3.5)cm,(16.9±3.4)min明显短于长切口组的(43.5±6.4)min,(31.7±5.9)min,差异均有统计学意义(P0.05)。两组大隐静脉壁的损伤情况比较无统计学差异(P0.05),但间断切口组术后下肢切口延迟愈合、感染、渗出、下肢血肿等并发症的发生率低于长切口组(P0.05)。结论:在冠状动脉旁路移植术中,间断切口获取大隐静脉能够显著缩短下肢手术切口长度,有助于减少术后下肢切口感染、延迟愈合、渗出、下肢血肿等并发症的发生。     

64层螺旋CTA在冠状动脉搭桥术后桥血管评价中的临床应用

目的：评价64层螺旋CTA在冠状动脉搭桥术后桥血管评价中的应用价值。方法：收集67例冠脉搭桥术后64层螺旋CTA资料,回顾性分析其成像条件、心电编辑软件对图像质量的影响;薄层容积图像及VR、CPP、MIP等后处理方法对桥血管的显示情况,并观察桥血管通畅状态。结果：67例CTA容积图像质量均满足诊断要求,其中15例经B受体阻滞剂控制心率;27例经过心电编辑软件后处理;检出正常桥血管107支,占74_31％（107／144）;异常静脉桥血管32支,22．22％（32／144）,包括近端吻合口尖角状闭塞13支,钙化斑块7支,软癍块8支,混合斑块1支;远端吻合口狭窄3支;正常动脉桥血管35支,24-31％（35／144）;异常动脉桥血管5支,3．47％（5／144）,包括闭塞内乳动脉桥血管4支,远端吻合口狭窄1支。上述多种后处理方法有助于多角度、多方位显示桥血管近、远端吻合口、桥血管行程及其与毗邻结构关系、有无斑块及管腔狭窄程度等。结论：64层螺旋CTA是冠脉搭桥术后评估桥血管状态准确、安全及简便的影像学检查方法。     

64 层螺旋CTA在冠状动脉搭桥术后桥血管评价中的临床应用

目的：评价64 层螺旋CTA 在冠状动脉搭桥术后桥血管评价中的应用价值。方法：收集67 例冠脉搭桥术后64 层螺旋CTA 资料,回顾性分析其成像条件、心电编辑软件对图像质量的影响;薄层容积图像及VR、CPP、MIP等后处理方法对桥血管的显示情 况,并观察桥血管通畅状态。结果：67 例CTA 容积图像质量均满足诊断要求,其中15 例经茁受体阻滞剂控制心率;27 例经过心 电编辑软件后处理;检出正常桥血管107 支,占74.31 %(107/144);异常静脉桥血管32 支,22.22 %(32/144),包括近端吻合口尖角 状闭塞13 支,钙化斑块7 支,软斑块8 支,混合斑块1 支;远端吻合口狭窄3 支;正常动脉桥血管35 支,24.31 %(35/144);异常动 脉桥血管5 支,3.47%(5/144),包括闭塞内乳动脉桥血管4 支,远端吻合口狭窄1 支。上述多种后处理方法有助于多角度、多方位 显示桥血管近、远端吻合口、桥血管行程及其与毗邻结构关系、有无斑块及管腔狭窄程度等。结论：64 层螺旋CTA 是冠脉搭桥术 后评估桥血管状态准确、安全及简便的影像学检查方法。     

Is there a haemodynamic advantage associated with cuffed arterial anastomoses?

The development of intimal hyperplasia at arterial bypass graft anastomoses is a major factor responsible for graft failure. A revised surgical technique, involving the incorporation of a small section of vein (vein cuff) into the distal anastomosis of PTFE grafts, results in an altered distribution of intimal hyperplasia and improved graft patency rates, especially for below-knee grafts. Numerical simulations have been conducted under physiological conditions to identify the flow behaviour in a typical cuffed bypass model and to determine whether the improved performance of the cuffed system can be accounted for by haemodynamic factors. The flow patterns at the cuffed anastomosis are significantly different to those at the conventional end-to-side anastomosis. In the former case, the flow is characterised by an expansive, low momentum recirculation within the cuff. Separation occurs at the graft heel, and at the cuff toe as the blood enters the recipient artery. Wall shear stresses in the vicinity of the cuff heel are low, but high shear stresses and large spatial gradients in the shearing force act on the artery floor during systole. In contrast, a less disturbed flow prevails and the floor shear stress distribution is less adverse in the conventional model. In conclusion, aspects of the anastomotic haemodynamics are worsened when the cuff is employed. The benefits associated with the cuffed grafts may be related primarily to the presence of venous material at the anastomosis. Therefore, caution is advised with regard to the use of PTFE grafts, pre-shaped to resemble a cuffed geometry.     

Simulation of flow through a Miller cuff bypass graft

Unnatural temporal and spatial distributions of wall shear stress in the anastomosis of distal bypass grafts have been identified as possible factors in the development of anastomotic intimal hyperplasia in these grafts. Distal bypass graft anastomoses with an autologus vein cuff (a Miller cuff) interposed between the graft and artery have been shown to alleviate the effects of intimal hyperplasia. In this study, pulsatile flow through models of a standard end-to-side anastomosis and a Miller cuff anastomosis are computed and the resulting wall shear stress and pressure distributions analysed. The results are inconclusive, and could be taken to suggest that the unnatural distributions of shear stress that do occur along the anastomosis floor may not be particularly important in the development of intimal hyperplasia. However, it seems more likely that the positive effects of the biological and material properties of the vein cuff, which are not considered in this study, somehow outweigh the negative effects of the shear stress distributions predicted to occur on the floor of the Miller-cuff graft.     

Simulation of Flow through a Miller Cuff Bypass Graft

Unnatural temporal and spatial distributions of wall shear stress in the anastomosis of distal bypass grafts have been identified as possible factors in the development of anastomotic intimal hyperplasia in these grafts. Distal bypass graft anastomoses with an autologus vein cuff (a Miller cuff) interposed between the graft and artery have been shown to alleviate the effects of intimal hyperplasia. In this study, pulsatile flow through models of a standard end-to-side anastomosis and a Miller cuff anastomosis are computed and the resulting wall shear stress and pressure distributions analysed. The results are inconclusive, and could be taken to suggest that the unnatural distributions of shear stress that do occur along the anastomosis floor may not be particularly important in the development of intimal hyperplasia. However, it seems more likely that the positive effects of the biological and material properties of the vein cuff, which are not considered in this study, somehow outweigh the negative effects of the shear stress distributions predicted to occur on the floor of the Miller-cuff graft.     

The clopidogrel after surgery for coronary artery disease (CASCADE) randomized controlled trial: clopidogrel and aspirin versus aspirin alone after coronary bypass surgery [NCT00228423]

Background

Saphenous vein graft disease remains a major limitation of coronary artery bypass graft surgery. The process of saphenous vein intimal hyperplasia begins just days after surgical revascularization, setting the stage for graft atherosclerotic disease and its sequalae. Clopidogrel improves outcomes in patients with atherosclerotic disease, and is effective at reducing intimal hyperplasia in animal models of thrombosis. Therefore, the goal of this study will be to evaluate the efficacy of clopidogrel and aspirin therapy versus aspirin alone in the prevention of saphenous vein graft intimal hyperplasia following coronary artery bypass surgery.

Methods

Patients undergoing multi-vessel coronary artery bypass grafting and in whom at least two saphenous vein grafts will be used are eligible for the study. Patients will be randomized to receive daily clopidogrel 75 mg or placebo, in addition to daily aspirin 162 mg, for a one year duration starting on the day of surgery (as soon as postoperative bleeding has been excluded). At the end of one year, all patients will undergo coronary angiography and intravascular ultrasound assessment of one saphenous vein graft as selected by randomization. The trial will be powered to test the hypothesis that clopidogrel and aspirin will reduce vein graft intimal hyperplasia by 20% compared to aspirin alone at one year following bypass surgery.

Discussion

This trial is the first prospective human study that will address the question of whether clopidogrel therapy improves outcomes and reduces saphenous vein graft intimal hyperplasia following cardiac surgery. Should the combination of clopidogrel and aspirin reduce the process of vein graft intimal hyperplasia, the results of this study will help redefine modern antiplatelet management of coronary artery bypass patients.     

A periadventitial sirolimus-releasing mesh decreased intimal hyperplasia in a rabbit model

Autologous vein grafts used as aortocoronary bypasses are often prone to intimal hyperplasia, which results in stenosis and occlusion of the vein. The aim of this study was to prevent intimal hyperplasia using a newly developed perivascular system with sustained release of sirolimus. This system of controlled drug release consists of a polyester mesh coated with a copolymer of L-lactic acid and epsilon-caprolactone that releases sirolimus. The mesh is intended for wrapping around the vein graft during surgery. The mesh releasing sirolimus was implanted in periadventitial position onto arteria carotis communis of rabbits, and neointimal hyperplasia was then assessed. We found that implanted sirolimus-releasing meshes reduced intima thickness by 47+/-10 % compared to a vein graft after 3 weeks. The pure polyester mesh decreased vein intima thickness by 35+/-9 %. Thus, our periadventitial system for controlled release of sirolimus prevented the development of intimal hyperplasia in autologous vein grafts in vivo in rabbits. A perivascularly applied mesh releasing sirolimus is a promising device for preventing stenosis of autologous vein grafts.     

Transitional flow at the venous anastomosis of an arteriovenous graft: potential activation of the ERK1/2 mechanotransduction pathway

We present experimental and computational results that describe the level, distribution, and importance of velocity fluctuations within the venous anastomosis of an arteriovenous graft. The motivation of this work is to understand better the importance of biomechanical forces in the development of intimal hyperplasia within these grafts. Steady-flow in vitro studies (Re = 1060 and 1820) were conducted within a graft model that represents the venous anastomosis to measure velocity by means of laser Doppler anemometry. Numerical simulations with the same geometry and flow conditions were conducted by employing the spectral element technique. As flow enters the vein from the graft, the velocity field exhibits flow separation and coherent structures (weak turbulence) that originate from the separation shear layer. We also report results of a porcine animal study in which the distribution and magnitude of vein-wall vibration on the venous anastomosis were measured at the time of graft construction. Preliminary molecular biology studies indicate elevated activity levels of the extracellular regulatory kinase ERK1/2, a mitogen-activated protein kinase involved in mechanotransduction, at regions of increased vein-wall vibration. These findings suggest a potential relationship between the associated turbulence-induced vein-wall vibration and the development of intimal hyperplasia in arteriovenous grafts. Further research is necessary, however, in order to determine if a correlation exists and to differentiate the vibration effect from that of flow related effects.     

Sequential venous anastomosis design to enhance patency of arterio-venous grafts for hemodialysis

Arterio-venous grafts (AVGs), the second best option as long-term vascular access for hemodialysis, face major issues of stenosis mainly due to development of intimal hyperplasia at the venous anastomosis which is linked to unfavorable hemodynamic conditions. We have investigated computationally the utility of a coupled sequential venous anastomotic design to replace conventional end-to-side (ETS) venous anastomosis, in order to improve the hemodynamic environment and consequently enhance the patency of AVGs. Two complete vascular access models with the conventional and the proposed venous anastomosis configurations were constructed. Three-dimensional, pulsatile blood flow through the models was simulated, and wall shear stress (WSS)-based hemodynamic parameters were calculated and compared between the two models. Simulation results demonstrated that the proposed anastomotic design provides: (i) a more uniform and smooth flow at the ETS anastomosis, without flow impingement and stagnation point on the artery bed and vortex formation in the heel region of the ETS anastomosis; (ii) more uniform distribution of WSS and substantially lower WSS gradients on the venous wall; and (iii) a spare route for the blood flow to the vein, to avoid re-operation in case of stenosis. The distinctive hemodynamic advantages observed in the proposed anastomotic design can enhance the patency of AVGs.     

Comparison of the hemodynamics in 6mm and 4-7 mm hemodialysis grafts by means of CFD

The aim of our study is to investigate with computational fluid dynamics (CFD) whether different arterial anastomotic geometries result in a different hemodynamics at the arterial (AA) and venous anastomosis (VA) of hemodialysis vascular access grafts. We have studied a 6mm graft (CD) and a 4-7 mm graft (TG). A validated three-dimensional CFD model is developed to simulate flow in the two graft types. Only the arterial anastomosis (AA) geometry differs. The boundary conditions applied are a periodic velocity signal at the arterial inlet and a periodic pressure wave at the venous outlet. Flow rate is set to 1,000 ml/min. The time dependent Navier-Stokes equations are solved. Wall shear stress (WSS), wall shear stress gradient (WSSG) and pressure gradient (PG) are calculated. Anastomotic flow is asymmetric although the anastomosis geometry is symmetric. The hemodynamic parameters, WSS, WSSG and PG, values at the suture line of the arterial anastomosis of the TG are at least twice as much as in the CD. Comparing the parameters at the two AA indicate that little flow rate increase introduces the risk of hemolysis in the TG whereas the CD is completely free of hemolysis. The hemodynamic parameter values at the venous anastomosis of the CD are 24 till 35% higher compared to the values of the TG. WSS values (> 3 Pa) in the VA are in the critical range for stenosis development in both graft geometries. The zones where the parameters reach extreme values correspond to the locations where intimal hyperplasia formation is reported in literature. In all anastomoses, the hemodynamic parameter levels are in the range where leucocytes and platelets get activated. Our simulations confirm clinical results where TG did not show a better outcome when compared to the CD.