动脉壁切应力在颈动脉狭窄中的作用

颈动脉分叉部动脉粥样硬化梗阻性疾病的起始与进展的血液动力学机制,在过去数十年被广泛研究。注意力集中在发现斑块最多的颈动脉球部或窦部。本文作者综述了颈动脉分叉部复杂的局部血液动力学改变,也包括了血液动力学改变所引起的特殊的细胞生物学反应的主要进展。这对于我们理解颈动脉窦部粥样硬化的血液动力学机制,改善血管内微创治疗与非创伤性治疗具有一定意义。     

一种可控性大鼠颈总动脉狭窄模型的建立及切应力测定

目的：为在体研究切应力改变诱导内皮细胞组织因了的表达建立一种可控性的大鼠颈总动脉狭窄模型。方法：54只SD大鼠随机分为9组，用自制硅胶管套扎左颈总动脉中段，术后不同时相点用TS 420型多普勒血流仪测定血流量，灌注前用DIGITEXα数字血管减影操作系统测定血管内径，用Poiseiuue流体力学公式Tw=32ηQ／πD^3计算切应力。结果：颈总动脉狭窄85％后，平均血流量减少了65％，局部切应力发生了显著变化（P〈0．01），在7d内无明显改变。结论：硅胶管套扎大鼠颈总动脉中段的狭窄模型，是比较理想的在体检测血流壁切应力改变对血管内皮细胞形态和功能影响的方法。     

二维脉动流场中内皮细胞表面切应力分布的数值模拟

本文对三种生理相关的正弦入口速度波形的脉动流场内,VEC表面的切应力分布进行了有限差分方法的数值模拟。结果表明：（1）脉动流场与稳态流场中内皮细胞表面的流场分布完全不同,脉动流场中内皮细胞表面的切应力变化幅度远大于稳态流场中的值。（2）同一时刻,每个VEC上的切应力分布是不均匀的,细胞形状影响其表面的切应力分布。（3）在脉动周期的不同时刻,细胞表面的切应力分布也是不均匀的,切应力分布随时间的变化波形与入口波形相类似,但相位有所超前,（4）细胞的伸长主要取决于EC表面的最大平均应力大小。（5）本章的计算结果可以用于Helmilinger实验现象的解释。     

利用硅胶管流动腔系统模拟动脉脉动血流切应力和周向应力环境

目的选择硅胶管流动腔的前、后负荷,模拟生理脉动流条件下动脉内皮细胞所承受的切应力和周向应力环境。方法利用在体脉动血流切应力和周向应力波形,在求得硅胶管流动腔几何和力学特性的情况下,反向求解硅胶管流动腔内径、压力和流量波形;根据所求得的压力和流量波形,确定出硅胶管流动腔的后负荷(即输入阻抗)条件;利用冯忠刚等提出的三弹性腔九元件集中参数模型模拟该后负荷,并求出各元件参数。结果三弹性腔九元件集中参数模型模拟出的输入阻抗模和幅角与目标输入阻抗模和幅角能较好的吻合。结论该方法为选择合适的硅胶管流动腔前、后负荷,构建能较真实再现动脉脉动血流切应力和周向应力环境的硅胶管流动腔系统提供了一定的理论依据。     

二维脉动流场中内皮细胞表面切应力分布的数值模拟

本文对三种生理相关的正弦入口速度波形的脉动流场内,VEC表面的切应力分布进行了有限差分方法的数值模拟.结果表明(1)脉动流场与稳态流场中内皮细胞表面的流场分布完全不同,脉动流场中内皮细胞表面的切应力变化幅值远大于稳态流场中的值.(2)同一时刻,每个VEC上的切应力分布是不均匀的,细胞形状影响其表面的切应力分布.(3)在脉动周期的不同时刻,细胞表面的切应力分布也是不均匀的,切应力分布随时间的变化波形与入口波形相类似,但相位有所超前.(4)细胞的伸长主要取决于EC表面的最大平均切应力大小.(5)本章的计算结果可以用于对Helmilinger实验现象的解释.     

复杂动脉血管内血液流动的研究进展

动脉硬化是一种严重影响人类健康的动脉血管常见病。大量的研究证明动脉硬化病灶的产生与动脉管壁的切应力分布有着密切的联系，其易友部位位于腹主动脉末端、冠状动脉、颈动脉分又等处。本文就动脉硬化的易发部位出发，对复杂动脉血管内血液流动的近期研究作一综述。     

S形动脉中的血流动力学研究

目的 探索动脉直径大小对S 形动脉血流动力学的影响。方法 利用数值模拟方法, 对具有不同直径的大小两种S 形动脉模型在相同的边界条件下的血流动力学时空分布进行了分析。结果 在大S形动脉中的二次流比小S形动脉中的要复杂; 在弯曲动脉的内弯区存在较强的涡流; 弯曲动脉中的压力和壁面切应力变化很剧烈, 特别是在大模型中。结论 S形弯曲动脉中的血流呈现复杂回流、二次流、压力和壁面切应力剧烈变化等特性, 这些都可能影响到动脉内皮的功能及内膜增生。在利用人造或自体血管修复旁路狭窄动脉的手术中, 应尽量避免采用S 形动脉模型。     

血流切应力对动脉内皮细胞凋亡影响的在体研究

探讨动脉血流受阻后壁切应力 (WSS)变化对动脉内皮细胞 (AEC)凋亡的影响。用 6 0只实验兔建立动脉血流减少模型 ,在术后 0～ 30 d 8个不同时点 ,AEC铺片 Tunel原位末端标记法 ,计量 AEC的凋亡率。结果发现 :在 WSS降低后 1～ 7d,AEC凋亡率显著增高 ,3d达到峰值。随着 WSS的递增 ,术后 14、30 d AEC的凋亡率又恢复至正常对照水平。提示 WSS的变化可显著影响 AEC的凋亡状况 ,其中 WSS的持续降低可能是诱导细胞凋亡的主要因素     

血管壁切应力变化对动脉内皮细胞间连接的影响

目的：探讨动脉血流受阻后管壁切应力变化对动脉内皮细胞连接的影响。方法：60只实验兔建立颈总动脉血流减少模型,在术后0至30天8个不同时相点,制作血流减小后的颈总动态超薄切片,透射电镜下观察内皮细胞间连接和细胞形态学变化。结果：动脉内皮细胞间连接结构及稳定性随血管壁切应力的变化而发生相应改变。3天后,在部分细胞间近腔面出现间隙;细胞间紧密连接不象正常对照那样完好而致密,胞质内未见微丝附着;可见部分动脉壁内皮细胞脱离基底膜或完全脱落人管腔。在血管壁切应力递增阶段,近腔面内皮细胞间隙消失,可见窄而短的闭锁带。结论：血管壁切应力的降低可导致动脉内皮细胞间连接结构发生改变,细胞稳定发生减小。提示低血流的切应力变化可能破坏动态内皮细胞屏蔽的完整性。     

血管粘弹性对法推拿作用下血管切应力的影响

目的研究血管粘弹性对脉动血流在(扌衮)法推拿作用下切应力的影响.方法建立具有局部轴向运动狭窄的粘弹性血管中脉动血流模型.设血液为牛顿流体,血管壁为线性粘弹体.在(扌衮)法推拿作用下血管受水平外力作用形成轴向运动缓变狭窄,血流遵循线化Navier-stokes方程.结果粘弹性血管在(扌衮)法作用下,距离血管入口z=31 cm处的平均切应力、最大切应力和瞬时切应力以及最大狭窄下游血管段最大切应力随着血管粘性系数和手法频率的改变而有较大变化.结论(扌衮)法推拿作用下粘弹性血管的血管切应力有显著变化,这与中医推拿的活血化淤相吻合.     

灌流式生物反应器内支架材料孔隙流场和壁面剪应力的数值分析

为获得支架材料孔隙受到的壁面剪应力的大小及分布、孔隙内压力分布以及支架材料与灌流小室之间不同缝隙时的灌流率。根据有限元方法建立了灌流式生物反应器小室内3种支架材料孔隙模型，用ansys软件分析了各种模型在不同工况下的灌流情况。结果表明，支架材料与灌流小室之间的孔隙决定灌流率，缝隙大于0.5mm时灌流率小于60％；支架材料孔隙壁面剪应力大小主要受灌流流量的影响，调节灌流流量是控制剪应力水平的主要手段。孔壁剪应力和孔内流体压力的分布均由支架材料孔隙的形状特征所决定。     

Numerical Simulation of Wall Shear Stress and Particle-Based Hemodynamic Parameters in Pre-Cuffed and Streamlined End-to-Side Anastomoses

A number of research studies have related multiple hemodynamic parameters to the formation of distal anastomotic intimal hyperplasia (IH) at the sub-cellular, cellular, and tissue levels. Focusing on mitigating WSS-based parameters alone, several studies have suggested geometrically modified end-to-side anastomoses with the intent of improving synthetic graft patency rates. However, recent clinical trials of commercially available versions of these grafts indicate persistently high rates of failure. Furthermore, recent evidence suggests that platelet-wall interactions may play a significant role in the formation of IH, which is not captured by WSS-based parameters alone. In this study, numerical simulations have been conducted to assess the potential for IH formation in conventional and geometrically modified anastomoses based on both wall shear stress (WSS) conditions and platelet-wall interactions. Sites of significant particle-wall interactions, including elevated concentrations and stasis, were identified by a near-wall residence time model, which includes factors for platelet activation and surface reactivity. Conventional, pre-cuffed, and streamlined distal end-to-side anastomoses were considered with proximal and distal arterial outflow. It was found that a pre-cuffed anastomosis, similar to the Distaflo configuration, does not offer a hemodynamic advantage over the conventional design considered with respect to the magnitude of the WSS field and the potential for platelet interactions with the vessel surface. Streamlined configurations largely consistent with venous confluences resulted in an advantageous reduction of wall shear stress gradient values; however, particle-wall interactions remained significant throughout the anastomosis. Results of this study are not intended to be directly extrapolated to surgical recommendations. However, these results highlight the difficulty associated with designing an end-to-side distal anastomosis with two-way outflow that is capable of simultaneously reducing multiple hemodynamic parameters. Further testing will be necessary to determine if the observed elevated particle-wall interactions in a pre-cuffed anastomosis provide the stimulus responsible for the reported high failure rates of these grafts.     

Arteries Respond to Independent Control of Circumferential and Shear Stress in Organ Culture

Arteries respond to changes in global mechanical parameters (pressure, flow rate, and longitudinal stretching) by remodeling to restore local parameters (circumferential stress, shear stress, and axial strain) to baseline levels. Because a change in a single global parameter results in changes of multiple local parameters, the effects of individual local parameters on remodeling remain unknown. This study uses a novel approach to study remodeling in organ culture based on independent control of local mechanical parameters. The approach is illustrated by studying the short term effects of circumferential and shear stress on remodeling-related biological markers. Porcine carotid arteries were cultured for 3 days at a circumferential stress of 50 or 150 kPa or, in separate experiments, a shear stress of 0.75 or 2.25 Pa. At high circumferential stress, matrix synthesis, smooth muscle cell proliferation, and cell death are significantly greater, but matrix metalloproteinase-2 (MMP-2) and pro-MMP-2 activity are significantly less. In contrast, biological markers measured were unaffected by shear stress. Applications of the proposed approach for improved understanding of remodeling, optimizing mechanical conditioning of tissue engineered arteries, and selection of experimentally motivated growth laws are discussed.     

出口边界条件和壁厚对冠状动脉壁面剪切力和冯米塞斯应力的影响

探讨基于个体化患者计算机断层血管造影(CTA)影像的冠状动脉流固耦合(FSI)数值分析中,不同出口边界条件和血管壁模型对时间平均壁面剪切力(TAWSS)和冯米塞斯应力(VMS)的影响。根据患者CTA影像重建右冠状动脉(RCA)管腔流域三维几何;将管腔流域表面向外扩张0.5 mm,形成均匀厚度血管壁;运用类似虚拟去除斑块的方法建立不均匀厚度血管壁模型。FSI分析时,分别给予zero和impedance两种出口边界条件;获得从舒张末期开始心动周期主要时间点TAWSS和VMS的分布,比较不同模型结果的差异。结果表明, 两种出口边界条件下,TAWSS空间分布基本一致,且血管狭窄段均高于其他部位;zero条件下峰值VMS出现在压强最大时刻点0.42 s,而impedance条件下峰值VMS出现在入口血流速度最大时刻点0.64 s,并且达到前者的20倍。同是impedance出口边界条件时,TAWSS分布基本一致,没有显著性差异;两种血管壁模型中,VMS的分布一致,血管狭窄段比其他部位低,但是不均匀厚度血管壁模型中局部位置VMS绝对值高于均匀壁厚血管壁模型。医学影像技术的发展可以提供更高精度的冠脉结构以及出入口速度和压强边界条件,不但对研究血流动力学以及结构力学因素与心血管疾病的关系具有重要意义,也可以更好的服务于患者个体化诊断与治疗。     

Effect of Cell-Free Layer Variation on Arteriolar Wall Shear Stress

Relationship between a cell-free layer and wall shear stress (WSS) in small arterioles has been of interest in microcirculatory research. However, influence of temporal variation in the cell-free layer width on the WSS in vivo has not been fully elucidated. In this study, we tested the hypothesis that the layer variation would increase the WSS, and this effect would be enhanced by red blood cell aggregation. The cell-free layer width in arterioles (29.5–67.1 μm ID) in rat cremaster muscles were obtained with a high-speed video camera, and the layer width data were introduced into WSS estimation. Dextran 500 was administrated to elevate the aggregation level of red blood cells to those seen in normal human blood. The variation of the layer was quantified by the variability (coefficient of variation), and its effect on WSS was studied under normal and reduced flow conditions. We found that the dextran-induced red blood cell aggregation significantly elevated the variability (p < 0.01) at low pseudoshear rates of 9.2 ± 0.6 s⁻¹. The WSS estimated without taking account of the variability showed underestimation of its value than that of with consideration of the variability under all flow conditions, and this effect became more pronounced with increasing the variability. The variation of the cell-free layer should, therefore, be considered in the determination of the WSS particularly in the presence of red blood cell aggregation under reduced flow condition.     

冠脉支架内再狭窄的血流动力学研究进展

冠脉支架术后再狭窄是严重且高发的医学事件。局部血流动力学因素,特别是壁面剪切应力(WSS),对冠脉粥样硬化斑块的形成、发展和不均匀性有着重要的影响。最近的基础和临床在体研究表明,WSS也可能与支架内再狭窄的发生有关。从支架内再狭窄的形成机制出发,分析冠脉支架后的力学环境对再狭窄的作用机制,详细阐述近年基于计算流体力学（CFD）方法的冠脉支架内再狭窄的血流动力学研究进展。     

Wall Shear Stress Modulation of ATP/ADP Concentration at the Endothelium

A mathematical model of ATP/ADP reaction at the surface of the endothelium for any two-dimensional or axisymmetric nonsingular functional form of the wall shear stress has been presented. Excellent agreement is obtained with the numerical solution for the parallel plate case. For spatially varying wall shear stress, such as the stagnation point flow and a backward facing step the ATP concentrations are shown to have a maximum at the stagnation point streamline and the reattachment point respectively. Increasing the Reynolds number increases both the ATP and ADP concentrations. For the backward facing step significant spatial variations occur in the concentration. Hence, a strong controlling factor for physiological kinetic values is the geometry of the arterial vessel since this determines the wall shear stress and thence the transport to the reactive surface. The area of high concentration also occurs where the wall shear stress is low (limiting case is zero shear stress). Atherosclerotic plaques are known to occur in areas of low wall shear stress and at vessel bifurcations where the wall shear stress is spatially varying. The ATP/ADP concentrations at these particular points may very well contribute to the formation of plaques. © 2003 Biomedical Engineering Society. PAC2003: 8719Tt, 8710+e, 8380Lz     

Influence of Vasoactive Drugs on Wall Shear Stress Distribution in the Abdominal Aortic Bifurcation: An In Vitro Study

The present study compares the wall shear stress (rate) distribution in a compliant aortic bifurcation model under three different hemodynamic states: normal state, angiotensin II infusion state (vasoconstrictor), and isoproterenol infusion state (vasodilator). Using a Newtonian blood analog fluid, flow wave forms corresponding to each flow state were generated in an in vitro flow loop and a photographic flow visualization technique was employed to measure wall shear rate. The results indicate a zone of low mean wall shear stress and highly oscillatory shear stress on the outer (lateral) wall of the bifurcation. In this zone, the mean wall shear stress became negative for all three hemodynamic states indicating flow separation. However, the spatial extent of the flow separation zone was not affected significantly by the flow state. The study also revealed a large spatial variation of the phase angle between the hoop strain (circumferential strain due to radial artery expansion) and the wall shear stress, the two main mechanical stimuli acting on endothelial cells which affect their biology. In the zone of low mean wall shear stress on the outer wall, the two stimuli were more out of phase relative to the mother branch, whereas they were less out of phase (by about 50°) on the inner wall (flow divider side). This phase angle was affected significantly by the flow state. For angiotensin II, the phase angle reached a maximum of 125° in the low mean shear zone while the maximum was 94° and 66° for the normal and isoproterenol states, respectively. Our observation that large phase angles between the hoop strain and wall shear stress wave forms are localized in the low shear stress region where atherosclerotic disease occurs suggests the possible physiological relevance of this phase angle to the development of atherosclerosis. © 1998 Biomedical Engineering Society. PAC98: 8745Hw