凝血酶调节蛋白基因防治血管内膜增生狭窄的实验研究

目的:观察凝血酶调节蛋白(Thrombomodulin,TM)基因转染兔髂动脉损伤模型后,对动脉血管内膜增生狭窄的防治作用。方法:用注射式加压转染的方式对兔动脉壁转染pcDNA3.1/hTM质粒,再制造动脉损伤-阻滞模型,于术后3天、7天、14天、28天用免疫组化的方法观察TM蛋白在各组血管腔内的表达,术后14天、28天用彩色多普勒观察活体吻合口内径和血流流速;再做病理切片Verhoeff染色,观察血管内膜增生的程度、部位,计算血管内膜面积、中膜面积和血管狭窄率。结果:术后3天、7天、14天、28天hTM质粒转染组中hTM表达一直保持在高水平,7天达到高峰,14天、28天虽有所下降但是表达强度仍然高于载体质粒转染组合空白对照组。在术后14天、28天彩色多普勒观察测量吻合口内径:hTM质粒转染组分别为1.93mm±0.34mm,1.89mm±0.28mm;载体质粒转染组为1.59mm±0.43mm,1.38mm±0.28mm;空白对照组1.46mm±0.25mm,1.44mm±0.32mm。在这两个时间点,hTM质粒转染组血管狭窄率为32±23%,37±14%;载体质粒转染组为58±21%,63±17%;空白对照组为58±19%,61±23%。结论:hTM基因在转染动脉壁后能减少动脉损伤-阻滞模型在后期的血管内膜增生,改善血管的狭窄状况。     

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。     

国产真丝涤纶人造血管的动物应用研究

目的：探讨国产真丝涤纶人造血管动物应用的可行性。方法：以真丝涤纶人造血管行犬的腹主动脉移植。结果：移植后１个月血管腔内表面形成不完善的内膜,外膜纤维组织明显增生;移植后３个月血管腔内表面完全内皮化,外膜部分肉芽组织胶原化;半年至１年内皮细胞排列更加整齐有序,吻合口轻度内膜增生,但无狭窄,外周为致密的纤维组织。结论：真丝涤纶人造血管作为新一代血管代用品是可行的,但其远期通畅率是有待进一步观察。     

以CT图像为基础的冠状动脉狭窄处血流动力学研究

目的:冠状动脉粥样硬化好发于具有特殊几何构型的血管部位,提示血流动力学参数在粥样硬化形成方面起到重要作用.以往研究多局限于理想的血管模型,本文旨在探索以CT图像为基础构建个体化冠状动脉血流动力学模型的技术方法,对人体左冠状动脉前降支粥样硬化病变狭窄处进行计算流体动力学(computational fluid dynamics,CFD)数值模拟,探讨冠状动脉粥样硬化病变形成和发展的血流动力学机制.方法:用MIMICS软件读取CTA数据,以CT图像为基础进行冠状动脉三维几何建模,假设动脉血流为层流、不可压缩、牛顿流体,入口血液流速随时间周期性变化,应用有限体积法FLUENT软件进行血流数值模拟,分析与动脉粥样硬化形成、发展相关的血流动力学参数.结果:获得个体化左冠状动脉前降支狭窄处血管模型及血流动力学参数,数值模拟结果包括冠状动脉的血液流场、壁面压力(wall pressure WP)及壁面切应力(wall shear stress WSS)分布,可见狭窄段血管血液流速加快,WP降低、WSS增高,且在狭窄邻近区域出现低WSS区、较高的WP及血液湍流区域.结论:以CT图像为基础的CFD技术是在体评价人狭窄冠状动脉内血流动力学状况与冠状动脉粥样硬化病变之间关系的有效方法,能够更为真实的建立人体血管几何模型,为分析血流动力学参数与冠状动脉粥样硬化形成与发展的关系提供研究手段.     

大鼠颈部自体静脉移植模型两种吻合方法的比较

目的比较间断吻合和连续吻合法建立静脉桥狭窄动物模型的优劣。方法SD大鼠20只,分成两组（间断吻合组和连续吻合组）,取颈外静脉与颈总动脉行端端吻合。术后4周取下静脉桥,观察桥管通畅性,分析新生内膜与中膜的厚度、面积比。结果连续组与间断组相比手术时间更短,出血更少,但桥管通畅率低,两组内膜增生程度没有显著差异。结论连续吻合用时短,出血少,对术者要求更高,较易形成吻合口狭窄。两者造模效果一样。     

血管镜下原位下肢动脉旁路术

作者经对27条肢体行动脉重建术,证明血管镜直视下可完全切开静脉移植物瓣膜,可准确定位结扎静脉属支,从而避免了术后动静脉瘘,避免了全程游离大隐静脉所造成的热缺血损伤并发症。血管镜可在术中监控移植物和吻合口质量。作者所设计应用的”复合移植物”和“共同流出道”技术有效地提高了静脉移植物的使用率,扩大了流出道的吻合口径和血流量。本组肢体救治率为25/27肢,在2～13个月随访期间吻合口均通畅,踝压由术前25.5±1.2mmHg上升为术后40.2±0.4mmHg,趾压由16.0±0.3上升为28.3±1.1(均值±S)。表明本手术在下肢动脉重建中具有良好的实用价值和独特的优点。     

一种带有旋动流引导器的新型小口径人造血管流场的数值模拟

大尺寸人造血管的临床应用已取得很大成功,但用于冠状动脉等旁路搭桥的小口径人造血管的急性血栓堵塞问题,至今仍未解决．因此,本文设计了一种可装于小口径人造血管前的旋流导引器,以期使进入人造血管内的血流产生旋动．对带有旋流导引器的人造血管内的血流流场进行了计算机数值模拟分析,并与常规人造血管内的血流流场进行了比较．数值模拟分析揭示,这种旋流导引器的确能使人造血管内的血流产生旋动,从而改变人造血管内的血流流场和流速分布,使近壁面血液的流速和壁面剪切应力得到极大提高．本研究认为,血液在人造血管壁面的流速和壁面剪切应力的提高,可抑制小口径人造血管内急性血栓的形成,从而达到提高小口径人造血管的通畅率的目的．     

Hippo信号通路在颈动脉结扎所致大鼠动脉血管重构中的表达及其意义

目的:在建立大鼠血管重构模型基础上探讨Hippo信号通路在该模型中的表达及意义。方法:模型组(n=40)经颈部正中切口游离出左侧颈总动脉,用6-0不可吸收线在尽量靠近近心端处结扎,完全阻断血流。对照组(n=20)仅将手术线穿过颈总动脉而不结扎,闭合切合。14 d后处死所有动物,经原手术路径分离颈总动脉,收集结扎处至远心端的动脉。用HE以及MASSON染色观察血管形态以及纤维化,免疫组织化学染色法检测颈动脉中α-肌动蛋白(α-MSA)和增殖细胞核抗原(PCNA)的表达,Western blot检测yes相关蛋白(YAP),PDZ结合基序的转录辅激活子(TAZ),TEAD1,Bax,Bcl-2的表达。结果:与对照组相比,造模组HE染色提示血管重构明显,新生内膜/中膜比例明显增加,MASSON染色提示纤维化明显增加;免疫组织化学染色法提示造模组血管α-MSA及PCNA表达明显增加; Western blot提示造模组血管YAP,TAZ,TEAD1,Bcl-2表达增加,而Bax表达降低,Bax/Bcl-2蛋白比例明显降低。结论:本研究成功建立颈动脉结扎介导的大鼠血管重构模型,另外证明Hippo信号通路在颈动脉结扎介导的大鼠血管重构模型中明显激活,以及可能介导增殖、凋亡相关的Bax/Bcl-2比值的改变,进而参与平滑肌细胞增殖促进血管重构。     

彩色多普勒超声联合血清β2-微球蛋白评估血管通路动静脉内瘘的临床价值分析

摘要 目的：探讨与分析彩色多普勒超声联合血清β2-微球蛋白评估血管通路动静脉内瘘的临床价值。方法：选择2019年1月-2022年6月在本院进行建立动静脉内瘘的血液透析患者210例作为研究对象,所有患者都在造瘘术前1d、术后3个月进行彩色多普勒超声检查与血清β2-MG检测,判断血管通路状况并进行相关性分析。结果：210例患者术后3个月的头静脉、桡动脉、内瘘口的内径、血流速度、血流量都明显高于术前1 d（P<0.05）。210例患者术后3个月的血清β2-微球蛋白含量明显低于术前1 d（P<0.05）。210例患者经过手术判定为动静脉内瘘异常22例,占比10.5 %,其中吻合口狭窄10例、内瘘头静脉端闭塞6例、静脉段血栓2例、吻合口血栓2例、静脉段狭窄2例。Spearsman分析显示动静脉内瘘异常与内瘘口血流速度、头静脉血流量、桡动脉内径、血清β2-微球蛋白含量存在相关性（P<0.05）。多因素logistic回归分析显示内瘘口血流速度、头静脉血流量、桡动脉内径、血清β2-微球蛋白含量为导致动静脉内瘘异常的重要因素（P<0.05）。结论：彩色多普勒超声可明确内瘘血流动力学和血管形态的变化,联合血清β2-微球蛋白检测可有效评估动静脉内瘘血管通路状况,监测内瘘使用功能与状态,为改善患者预后提供参考依据。     

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。     

An S-type bypass can improve the hemodynamics in the bypassed arteries and suppress intimal hyperplasia along the host artery floor

The development of distal end-to-side anastomotic intimal hyperplasia (IH) has been attributed to the flow disturbance and abnormal wall shear stress (WSS) distribution there. The geometry of the bypass has a strong influence on the flow pattern and WSS distribution. Using a canine model of end-to-side anastomosis, a 45 degrees S-type bypass was compared with 60 degrees , 45 degrees and 30 degrees conventional bypasses in the term of IH along the host artery floor. Numerical blood flow simulations were also carried out to characterize the flow patterns at the distal parts of the bypassed arteries for the 4 models. The results showed that the averaged intima thicknesses of the host artery floors for the 4 bypass models were 119.50+/-10.30 microm (60 degrees ), 65.56+/-6.53 microm (45 degrees ), 45.26+/-5.99 microm (30 degrees ) and 47.64+/-4.85 microm (S-type), respectively, vs. 9.81+/-1.88 microm in the control group (without bypass surgery). Compared with the control group, neointima thickness in all 4 bypass models was significantly increased, but the neointima thickness of the 45 degrees S-type bypass was apparently much better than its 45 degrees conventional counterpart, and was as good as the 30 degrees conventional bypass. The numerical simulation revealed an apparent swirling flow pattern in the S-type bypass, which was very different than the flow patterns in the 3 conventional bypass models. This swirling flow altered the overall flow pattern in the distal part of the bypassed artery and eliminated the low WSS zone along the host artery floor. The improvement in the term of IH for the S-type bypass is most likely due to the alteration of the overall flow pattern and WSS distribution by the geometrical configuration of the S-type bypass.     

Hemodynamic factors at the distal end-to-side anastomosis of a bypass graft with different POS:DOS flow ratios

A pulsatile flow in vitro model of the distal end-to-side anastomosis of an arterial bypass graft was used to examine the effects that different flow ratios between the proximal outlet segment (POS) and the distal outlet segment (DOS) have on the flow patterns and the distributions of hemodynamic factors in the anastomosis. Amberlite particles were tracked by flow visualization to determine overall flow patterns and velocity measurements were made with Laser Doppler anemometry (LDA) to obtain detailed hemodynamic factors along the artery floor and the graft hood regions. These factors included wall shear stress (WSS), spatial wall shear stress gradient (WSSG), and oscillatory index (OSI). Statistical analysis was used to compare these hemodynamic factors between cases having different POS:DOS flow ratios (Case 1-0:100, Case 2-25:75, Case 3-50:50). The results showed that changes in POS:DOS flow ratios had a great influence on the flow patterns in the anastomosis. With an increase in proximal outlet flow, the range of location of the stagnation point along the artery floor decreased, while the extent of flow separation along the graft hood increased. The statistical results showed that there were significant differences (p<0.05) for the mean WSS between cases along the graft hood, but no significant differences were detected along the artery floor. There were no significant differences for the spatial WSSG along both the artery floor and the graft hood. However, there were significant differences (p<0.05) in the mean OSI between Cases 1 and 2 and between Cases 1 and 3 both along the artery floor and along the graft hood. Comparing these mechanical factors with histological findings of intimal hyperplasia formation obtained by previous canine studies, the results of the statistical analysis suggest that regions exposed to a combination of low mean WSS and high OSI may be most prone to the formation of intimal hyperplasia.     

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 effect of proximal artery flow on the hemodynamics at the distal anastomosis of a vascular bypass graft: computational study

The formation of distal anastomotic intimal hyperplasia (IH), one common mode of bypass graft failure, has been shown to occur in the areas of disturbed flow particular to this site. The nature of theflow in the segment of artery proximal to the distal anastomosis varies from case to case depending on the clinical situation presented. A partial stenosis of a bypassed arterial segment may allow residual prograde flow through the proximal artery entering the distal anastomosis of the graft. A complete stenosis may allow for zero flow in the proximal artery segment or retrograde flow due to the presence of small collateral vessels upstream. Although a number of investigations on the hemodynamics at the distal anastomosis of an end-to-side bypass graft have been conducted, there has not been a uniform treatment of the proximal artery flow condition. As a result, direct comparison of results from study to study may not be appropriate. The purpose of this work was to perform a three-dimensional computational investigation to study the effect of the proximal artery flow condition (i.e., prograde, zero, and retrograde flow) on the hemodynamics at the distal end-to-side anastomosis. We used the finite volume method to solve the full Navier-Stokes equations for steady flow through an idealized geometry of the distal anastomosis. We calculated the flow field and local wall shear stress (WSS) and WSS gradient (WSSG) everywhere in the domain. We also calculated the severity parameter (SP), a quantification of hemodynamic variation, at the anastomosis. Our model showed a marked difference in both the magnitude and spatial distribution of WSS and WSSG. For example, the maximum WSS magnitude on the floor of the artery proximal to the anastomosis for the prograde and zero flow cases is 1.8 and 3.9 dynes/cm2, respectively, while it is increased to 10.3 dynes/cm2 in the retrograde flow case. Similarly, the maximum value of WSSG magnitude on thefloor of the artery proximal to the anastomosis for the prograde flow case is 4.9 dynes/cm3, while it is increased to 13.6 and 24.2 dynes/cm3, respectively, in the zero and retrograde flow cases. The value of SP is highest for the retrograde flow case (13.7 dynes/cm3) and 8.1 and 12.1 percent lower than this for the prograde (12.6 dynes/cm3) and zero (12.0 dynes/cm3) flow cases, respectively. Our model results suggest that the flow condition in the proximal artery is an important determinant of the hemodynamics at the distal anastomosis of end-to-side vascular bypass grafts. Because hemodynamic forces affect the response of vascular endothelial cells, the flow situation in the proximal artery may affect IH formation and, therefore, long-term graft patency. Since surgeons have some control over the flow condition in the proximal artery, results from this study could help determine which flow condition is clinically optimal.     

Non-Newtonian effects of blood flow on hemodynamics in distal vascular graft anastomoses

Non-Newtonian fluid flow in a stenosed coronary bypass is investigated numerically using the Carreau-Yasuda model for the shear thinning behavior of the blood. End-to-side coronary bypass anastomosis is considered in a simplified model geometry where the host coronary artery has a 75% severity stenosis. Different locations of the bypass graft to the stenosis and different flow rates in the graft and in the host artery are studied. Particular attention is given to the non-Newtonian effect of the blood on the primary and secondary flow patterns in the host coronary artery and the wall shear stress (WSS) distribution there. Interaction between the jet flow from the stenosed artery and the flow from the graft is simulated by solving the three-dimensional Navier-Stokes equation coupled with the non-Newtonian constitutive model. Results for the non-Newtonian flow, the Newtonian flow and the rescaled Newtonian flow are presented. Significant differences in axial velocity profiles, secondary flow streamlines and WSS between the non-Newtonian and Newtonian fluid flows are revealed. However, reasonable agreement between the non-Newtonian and the rescaled Newtonian flows is found. Results from this study support the view that the residual flow in a partially occluded coronary artery interacts with flow in the bypass graft and may have significant hemodynamic effects in the host vessel downstream of the graft. Non-Newtonian property of the blood alters the flow pattern and WSS distribution and is an important factor to be considered in simulating hemodynamic effects of blood flow in arterial bypass grafts.     

The effect of graft caliber upon wall shear within in vivo distal vascular anastomoses

Wall shear has been widely implicated as a contributing factor in the development of intimal hyperplasia in the anastomoses of chronic arterial bypass grafts. Earlier studies have been restricted to either: (1) in vitro or computer simulation models detailing the complex hemodynamics within an anastomosis without corresponding biological responses, or (2) in vivo models that document biological effects with only approximate wall shear information. Recently, a specially designed pulse ultrasonic Doppler wall shear rate (PUDWSR) measuring device has made it possible to obtain three near-wall velocity measurements nonintrusively within 1.05 mm of the vessel luminal surface from which wall shear rates (WSRs) were derived. It was the purpose of this study to evaluate the effect of graft caliber, a surgically controllable variable, upon local hemodynamics, which, in turn, play an important role in the eventual development of anastomotic hyperplasia. Tapered (4-7 mm I.D.) 6-cm-long grafts were implanted bilaterally in an end-to-side fashion with 30 deg proximal and distal anastomoses to bypass occluded common carotid arteries of 16 canines. The bypass grafts were randomly paired in contralateral vessels and placed such that the graft-to-artery diameter ratio, DR, at the distal anastomosis was either 1.0 or 1.5. For all grafts, the average Re was 432 +/- 112 and the average Womersley parameter, alpha, was 3.59 +/- 0.39 based on artery diameter. There was a sharp skewing of flow toward the artery floor with the development of a stagnation point whose position varied with time (up to two artery diameters) and DR (generally more downstream for DR = 1.0). Mean WSRs along the artery floor for DR = 1.0 and 1.5 were found to range sharply from moderate to high retrograde values (589 s-1 and 1558 s-1, respectively) upstream to high antegrade values (2704 s-1 and 2302 s-1, respectively) immediately downstream of the stagnation point. Although there were no overall differences in mean and peak WSRs between groups, there were significant differences (p < 0.05) in oscillatory WSRs as well as in the absolute normalized mean and peak WSRs between groups. There were also significant differences (p < 0.05) in mean and peak WSRs with respect to axial position along the artery floor for both DR cases. In conclusion, WSR varies widely (1558 s-1 retrograde to 2704 s-1 antegrade) within end-to-side distal graft anastomoses, particularly along the artery floor, and may play a role in the development of intimal hyperplasia through local alteration of mass transport and mechano-signal transduction within the endothelium.     

Three-dimensional numerical simulations of flow through a stenosed coronary bypass

This work analyzes the flow patterns at the anastomosis of a stenosed coronary bypass. Three-dimensional numerical simulations are performed using a finite elements method. We consider a geometrical model of the host coronary artery with and without a 75% severity stenosis for three different locations from the anastomosis. The flow features - velocity profiles, secondary motions and wall shear stresses - are compared for different configurations of the flow rate and of the distance of the anastomosis from the site of occlusion (called distance of grafting). The combination of the junction flow effects - counter rotating vortices - with the stenosis effects - confined jet flow - is particularly important when the distance of grafting is short. Given that the residual flow issued from the pathologic stenosis being non-negligible after two weeks grafting, models without stenosis cannot predict the evolution of the wall shear stress in the vicinity of the anastomosis.     

Computational model of blood flow in the aorto-coronary bypass graft

Background

Coronary artery bypass grafting surgery is an effective treatment modality for patients with severe coronary artery disease. The conduits used during the surgery include both the arterial and venous conduits. Long- term graft patency rate for the internal mammary arterial graft is superior, but the same is not true for the saphenous vein grafts. At 10 years, more than 50% of the vein grafts would have occluded and many of them are diseased. Why do the saphenous vein grafts fail the test of time? Many causes have been proposed for saphenous graft failure. Some are non-modifiable and the rest are modifiable. Non-modifiable causes include different histological structure of the vein compared to artery, size disparity between coronary artery and saphenous vein. However, researches are more interested in the modifiable causes, such as graft flow dynamics and wall shear stress distribution at the anastomotic sites. Formation of intimal hyperplasia at the anastomotic junction has been implicated as the root cause of long- term graft failure.Many researchers have analyzed the complex flow patterns in the distal sapheno-coronary anastomotic region, using various simulated model in an attempt to explain the site of preferential intimal hyperplasia based on the flow disturbances and differential wall stress distribution. In this paper, the geometrical bypass models (aorto-left coronary bypass graft model and aorto-right coronary bypass graft model) are based on real-life situations. In our models, the dimensions of the aorta, saphenous vein and the coronary artery simulate the actual dimensions at surgery. Both the proximal and distal anastomoses are considered at the same time, and we also take into the consideration the cross-sectional shape change of the venous conduit from circular to elliptical. Contrary to previous works, we have carried out computational fluid dynamics (CFD) study in the entire aorta-graft-perfused artery domain. The results reported here focus on (i) the complex flow patterns both at the proximal and distal anastomotic sites, and (ii) the wall shear stress distribution, which is an important factor that contributes to graft patency.

Methods

The three-dimensional coronary bypass models of the aorto-right coronary bypass and the aorto-left coronary bypass systems are constructed using computational fluid-dynamics software (Fluent 6.0.1). To have a better understanding of the flow dynamics at specific time instants of the cardiac cycle, quasi-steady flow simulations are performed, using a finite-volume approach. The data input to the models are the physiological measurements of flow-rates at (i) the aortic entrance, (ii) the ascending aorta, (iii) the left coronary artery, and (iv) the right coronary artery.

Results

The flow field and the wall shear stress are calculated throughout the cycle, but reported in this paper at two different instants of the cardiac cycle, one at the onset of ejection and the other during mid-diastole for both the right and left aorto-coronary bypass graft models. Plots of velocity-vector and the wall shear stress distributions are displayed in the aorto-graft-coronary arterial flow-field domain. We have shown (i) how the blocked coronary artery is being perfused in systole and diastole, (ii) the flow patterns at the two anastomotic junctions, proximal and distal anastomotic sites, and (iii) the shear stress distributions and their associations with arterial disease.

Conclusion

The computed results have revealed that (i) maximum perfusion of the occluded artery occurs during mid-diastole, and (ii) the maximum wall shear-stress variation is observed around the distal anastomotic region. These results can enable the clinicians to have a better understanding of vein graft disease, and hopefully we can offer a solution to alleviate or delay the occurrence of vein graft disease.

     

Intimal hyperplasia and wall shear in arterial bypass graft distal anastomoses: an in vivo model study

The observation of intimal hyperplasia at bypass graft anastomoses has suggested a potential interaction between local hemodynamics and vascular wall response. Wall shear has been particularly implicated because of its known effects upon the endothelium of normal vessels and, thus, was examined as to its possible role in the development of intimal hyperplasia in arterial bypass graft distal anastomoses. Tapered (4-7 mm I.D.) e-PTFE synthetic grafts 6 cm long were placed as bilateral carotid artery bypasses in six adult, mongrel dogs weighing between 25 and 30 kg with distal anastomotic graft-to-artery diameter ratios (DR) of either 1.0 or 1.5. Immediately following implantation, simultaneous axial velocity measurements were made in the toe and artery floor regions in the plane of the anastomosis at radial increments of 0.35 mm, 0.70 mm, and 1.05 mm using a specially designed 20 MHz triple crystal ultrasonic wall shear rate transducer Mean, peak, and pulse amplitude wall shear rates (WSRs), their absolute values, the spatial and temporal wall shear stress gradients (WSSG), and the oscillatory shear index (OSI) were computed from these velocity measurements. All grafts were harvested after 12 weeks implantation and measurements of the degree of intimal hyperplasia (IH) were made along the toe region and the artery floor of the host artery in 1 mm increments. While some IH occurred along the toe region (8.35+/-23.1 microm) and was significantly different between DR groups (p<0.003), the greatest amount occurred along the artery floor (81.6+/-106.5 microm, mean +/- S.D.) (p < 0.001) although no significant differences were found between DR groups. Linear regressions were performed on the paired IH and mean, peak, and pulse amplitude WSR data as well as the absolute mean, peak, and pulse amplitude WSR data from all grafts. The mean and absolute mean WSRs showed a modest correlation with IH (r = -0.406 and -0.370, respectively) with further improvements seen (r = -0.482 and -0.445, respectively) when using an exponential relationship. The overall best correlation was seen against an exponential function of the OSI (r = 0.600). Although these correlation coefficients were not high, they were found to be statistically significant as evidenced by the large F-statistic obtained. Finally, it was observed that over 75 percent of the IH occurred at or below a mean WSR value of 100 s(-1) while approximately 92 percent of the IH occurred at or below a mean WSR equal to one-half that of the native artery. Therefore, while not being the only factor involved, wall shear (and in particular, oscillators wall shear) appears to provide a stimulus for the development of anastomotic intimal hyperplasia.