管壁切应力在冠状动脉粥样硬化中的重要作用:狭窄冠状动脉的有限元研究

目的基于冠状动脉CT造影数据建立不同狭窄程度冠状动脉的有限元模型,并进行流体力学模拟研究,分析管壁切应力(WSS)的变化情况及其在动脉粥样硬化中的关键作用。方法利用临床患者狭窄冠状动脉的冠状动脉CT造影数据,建立精确解剖的三维模型;再使用有限元软件建立有限元模型,设置各种边界条件进行模拟分析;最后采用各种图形形式输出结果,进行分析研究。结果冠状动脉狭窄处WSS明显升高,且随着血管狭窄程度的增加而逐渐升高;狭窄后区域WSS减低,与血管狭窄程度呈反比,二者之间存在切应力梯度,且随着血管狭窄程度的增加逐渐增大。结论 WSS的变化会导致粥样斑块的发生发展,在动脉粥样硬化的发病机制中扮演着重要的角色。     

不同形态低切应力对小鼠腹主动脉重构及内皮P选择素表达的影响

目的 制备小鼠腹主动脉狭窄的实验模型,探讨短期不同形态的低剪切应力对动脉重建及内皮P选择素表达的影响.方法 24只小鼠随机平均分为3个实验组(1h组、4h组、24h组)和1个正常对照组,实验组用动脉银夹建立腹主动脉局部狭窄模型,彩色多普勒超声检测狭窄近心端和远心端血流动力学参数,计算切应力值;血管标本行HE染色和内皮P选择素免疫组织化学染色,定量分析动脉病理形态学的改变和半定量分析内皮P选择素表达的强度.结果 狭窄动脉近心端和远心端血流分别形成低切应力区和振荡性低切应力涡流区,并且在所有观察点狭窄动脉近心端和远心端血管发生不同程度的动脉重建与内皮P选择素表达,但近心端较远心端更明显(P<0.05).结论 血流动力学改变在较短的时间内可引起动脉重构及内皮P选择素的表达,而且不同形态低切应力导致的病变程度是不同的.     

剪切应力对家兔血管内膜增生及动脉粥样硬化斑块形成的影响

目的设计局部狭窄而导致血流动力学改变的实验模型,探讨剪切应力对血管内膜增生以及动脉粥样硬化斑块形成的影响。方法兔颈总动脉平直段套环形成狭窄度为40%的局部狭窄,饲以正常饮食4周;数值计算的方法模拟血流流场和剪切应力分布及其特征;HE染色检测颈总动脉病理改变;Verhoeff法染色观察血管弹力纤维分布;油红O染色观察斑块内的脂质沉积;高效液相色谱检测血管壁脂质含量。结果套环形成局部狭窄后,颈总动脉血流流场发生显著的扰动,狭窄远心端有涡流以及二次流形成;狭窄近心端形成局部高剪切应力区域(6Pa),而在远心端形成振荡的低剪切应力区域(0～0.3Pa);HE染色显示颈总动脉狭窄的近心端和远心端均有明显的内膜增生以及动脉粥样硬化斑块形成,近心端比远心端病变更严重,近心端增生内膜厚度为165.6±28.3μm,远心端增生内膜厚度为38.5±12.7μm,并且近心端增生内膜的细胞成分主要为圆形的泡沫细胞而远心端增生内膜的细胞成分主要为梭形平滑肌细胞;Verhoeff染色显示病变处弹力纤维排列紊乱,部分内弹力板断裂;油红O染色发现增生的斑块中有大量的脂质沉积;高效液相色谱检测也表明狭窄近心端胆固醇含量(7.6±2.1mg/g)以及远心端胆固醇含量(5.6±1.8mg/g)较对照侧(1.3±0.5mg/g)明显增加。结论高剪切应力以及低振荡剪切应力均引发动脉粥样硬化病变的形成,但不同的剪切应力对斑块的组成和特性有着不同的作用。     

基于减影技术的冠状动脉CT血流储备分数对钙化所致狭窄血流动力学的诊断价值

目的 探讨基于减影技术的冠状动脉CT血流储备分数(CT-FFR)诊断钙化病变所致冠状动脉血流动力学狭窄的价值。方法 前瞻性纳入2020年3月至2022年3月中国医学科学院北京协和医院就诊并确诊或拟诊冠心病患者22例,42处病变纳入分析。准备行有创冠状动脉造影检查的患者,提供减影冠状动脉CT血管造影(CCTA)检查,CCTA图像重建算法采用混合迭代重建。存在钙化所致冠状动脉中重度狭窄患者提供FFR检查,FFR值≤0.80定义为血流动力学显著狭窄。以FFR为金标准,计算CCTA、减影CCTA、CT-FFR和减影CT-FFR诊断钙化斑块所致血流动力学狭窄效能。结果 以病变为单位分析显示,4种图像中减影CT-FFR的诊断效能最高,敏感性、特异性、阳性预测值、阴性预测值和准确性分别为100.0%、62.1%、54.2%、100.0%和73.8%,ROC曲线下面积为0.83。以患者为单位分析显示,4种图像中减影CT-FFR的诊断效能最高,敏感性、特异性、阳性预测值、阴性预测值和准确性分别为100.0%、33.3%、55.6%、100.0%和63.6%,ROC曲线下面积为0.77。结论 减影CT-F...     

凝集素样氧化型低密度脂蛋白受体在兔颈动脉狭窄模型中的表达及血流动力的作用

目的 探讨凝集素样氧化型低密度脂蛋白受体在兔颈动脉狭窄模型中的表达及血流动力的作用.方法 健康日本大耳白兔15只,随机分为狭窄组、高脂组、对照组,每组5只.狭窄组及高脂组采用显微缝合加高脂饮食法建立实验性兔颈动脉狭窄模型,对照组给予标准饲料.共12 w.多普勒超声检测狭窄血管的血流动力学参数,采用RT-PCR检测狭窄近心端、狭窄处及狭窄远心端LOX-1表达.结果 在颈动脉狭窄处及狭窄远心端分别形成高切应力和低切应力区.高脂环境下LOX-1表达有升高趋势,LOX-1在血管狭窄处及狭窄远心端呈高表达.结论 血管狭窄后血流动力学改变影响LOX-1表达,低切应力水平促进LOX-1表达.     

低密度脂蛋白浓度极化对动脉粥样硬化形成的影响及其机制

目的为进一步证实和探讨LDL浓度极化在动脉粥样硬化局灶性中的作用。方法以狭窄血管远心端为研究对象,采用数值模拟及粒子图象测速法分别模拟和测定狭窄血管远心端流场分布及其特点;数值模拟及激光共聚焦显微镜分别模拟和测定狭窄血管远心端壁面LDL浓度分布;采用外科手术的方法     

异常剪切应力上调组织蛋白酶L在动脉粥样硬化斑块中表达

目的观察组织蛋白酶L(Cathepsin L)在异常剪切切应力诱导的动脉粥样硬化斑块中的表达,探讨Cathepsin L在动脉粥样硬化病变中的作用。方法采用套环法建立兔颈总动脉局部狭窄的动物模型,喂养4周;数值模拟法模拟局部狭窄远心端和近心端流场特性以及剪切应力分布;酶法测定血浆中总胆固醇、甘油三酯以及HDL水平;HE染色观察病理学改变;油红O染色观察病变处脂质的蓄积;免疫组织化学法检测Cathepsin L的表达。结果 4周后,兔血脂水平没有明显改变。套环形成局部狭窄后,颈总动脉血流流场发生显著的扰动,狭窄远心端有涡流以及二次流形成;狭窄近心端形成局部高剪切应力区域,而在远心端形成振荡的低剪切应力区域(0～0.3 Pa)。HE染色显示颈总动脉狭窄的近心端和远心端均有明显的内膜增生以及动脉粥样硬化斑块形成,近心端比远心端病变更严重。油红O染色显示有大量的脂质沉积;免疫组织化学染色结果表明病变中有大量的Cathepsin L表达,主要分布于斑块中的巨噬细胞和平滑肌细胞,并且近心端Cathepsin L的表达量明显高于远心端量,而对照侧血管仅有微量的Cathepsin L表达。结论切应力特性调节Cathepsin...     

载瘤动脉狭窄对颈内-后交通动脉动脉瘤血流动力学影响的初步分析

目的 评价瘤颈近端载瘤动脉狭窄对颈内-后交通动脉动脉瘤血流动力学的影响.方法 回顾性连续纳入2018年1—6月海军军医大学附属第一医院神经外科收治的颅内动脉瘤患者438例,其中颈内-后交通动脉动脉瘤患者74例,排除了未合并载瘤动脉狭窄患者55例,发生载瘤动脉痉挛1例,三维影像资料不全8例,数据无法满足血流动力学分析要求2例,最终纳入合并瘤颈近端(狭窄距动脉瘤颈1 cm以内)载瘤动脉狭窄的颈内-后交通动脉动脉瘤住院患者8例,其中男3例,女5例;年龄49~77岁,平均(63±11)岁.根据患者DSA三维重组后载瘤动脉狭窄形态,将8例患者分为偏心性狭窄组和同心圆性狭窄组,每组4例.构建基于病例特异性的三维动脉瘤模型,采用计算机软件模拟载瘤动脉不同狭窄程度(近端载瘤动脉分别模拟30%、50%、70%、90%四种狭窄程度)和不同狭窄距离(在距离动脉瘤1 cm内的近端载瘤动脉上分别选取2.5、5.0、7.5、10.0 mm四个距离),计算动脉瘤壁面切应力(WSS)和血流速度.采用线性混合效应模型对多水平数据进行分析.结果 (1)对偏心性狭窄组进行分析显示,狭窄距离每增加2.5mm,估计动脉瘤WSS平均降低1.040 Pa,估计狭窄处血流速度平均降低33.333 m/s(均P=0.01);狭窄程度每增加20%,估计动脉瘤WSS平均增加23.988 Pa,估计狭窄处血流速度平均增加0.485 m/s,差异均有统计学意义(均P<0.01).(2)对同心圆性狭窄组进行分析显示,狭窄距离每增加2.5 mm,估计动脉瘤WSS平均降低1.109 Pa,估计狭窄处血流速度平均降低29.412 m/s,差异均有统计学意义(均P<0.01);狭窄程度每增加20%,估计动脉瘤WSS平均增加19.099 Pa,估计狭窄处血流速度平均增加0.524m/s,差异均有统计学意义(均P<0.01).结论 载瘤动脉狭窄程度的增加可导致动脉瘤WSS增大,可能与颈内-后交通动脉动脉瘤进展有关.改善狭窄程度可有效降低动脉瘤WSS,但能否延缓甚至逆转动脉瘤的进展过程尚需进一步随访、验证.     

椎基底动脉迂曲扩张症的计算流体力学分析

目的 基于磁共振血管造影(MRA)的椎基底动脉迂曲扩张症(VBD)计算机流体力学分析。方法 选取2018年1月至2022年1月牡丹江医学院附属红旗医院诊断为VBD的40例患者,经MRI检查正常的40例患者图像。以椎基底动脉MRA图像构建椎基底动脉三维几何模型,分为VBD组与对照组,分析血流速度(V)、壁面剪切应力(WSS)及震荡剪切系数(OSI)。结果 VBD组V、WSS及OSI均高于对照组,差异有统计学意义(P <0.05)。在血流速度方面,高速血流集中于基底动脉及右侧大脑后动脉处。在WSS方面,VBD组高WSS位于右侧椎动脉、基底动脉、双侧大脑后动脉等大部分血管区域,以血管分叉处显著。在OSI方面,VBD组高OSI值以基底动脉末端至双侧大脑后动脉发出处明显,其余血管区域为波动性高OSI分布。结论 基于真实磁共振患者图像可建立三维个体化血管模型及进行血流动力学分析,获取VBD血流速度图、血管剪切应力云图及震荡剪切系数云图。建立VBD组及对照组模型,分析血流动力学发现,VBD组的基底动脉段具有高速血流、高WSS及高OSI,以末端显著,临床上应着重关注此区域。     

基于人工智能的CT-FFR与冠状动脉狭窄的相关性分析

目的]应用基于人工智能的CT-血流储备分数(CT-FFR)探讨冠心病患者冠状动脉狭窄程度、钙化积分与冠状动脉血流动力学的相关性。[方法]回顾性收集206例青海大学附属医院2020年9月—2021年4月接受冠状动脉CT血管成像(CCTA)的疑似冠心病患者的临床及影像资料,通过人工智能软件分析患者的左前降支、左回旋支、右冠状动脉的CT-FFR值、钙化积分及狭窄程度,根据CT-FFR值将所有患者分为两组:有功能意义组(CT-FFR≤0.8)和无功能意义组(CT-FFR＞0.8),分析两组间冠状动脉狭窄程度、钙化积分与冠状动脉血流动力学的相关性。[结果]206例患者共有365支血管纳入研究,其中有功能意义组139支血管,无功能意义组226支血管。CT-FFR与狭窄程度(r＝－0.473,P＜0.001)、钙化积分(r＝－0.369,P＜0.001)呈中度负相关,钙化积分与狭窄程度呈极弱正相关(r＝0.141,P＝0.007)。与无功能意义组相比,有功能意义组患者男性占比高,发病年龄大,高血压、吸烟史比例均更高。[结论]冠状动脉狭窄程度和钙化积分是造成冠状动脉血流动力学异常的重要因素,CT-FFR有助于CCTA在冠状动脉病变中的功能学评估。     

前交通动脉动脉瘤支架治疗后血管形态及流体力学数值的模拟研究

目的探讨支架置入治疗前交通动脉宽颈动脉瘤对动脉瘤转归的影响。方法对1例应用支架辅助栓塞前交通动脉宽颈动脉瘤的患者,通过计算流体力学（CFD）有限元方法软件,重建三维血管模型。于支架置入前,截取动脉瘤并修补瘤颈部对应的血管壁,模拟单纯弹簧圈致密栓塞的结果。对比支架置入前后的血管形态改变,分析不同血管形态下的血流动力学参数,包括血液流线、压力及壁面切应力（WSS）等。结果①与单纯弹簧圈致密栓塞对比,支架置入后,血管形态发生明显改变,同侧大脑前动脉A1段和A2段血管夹角增加14．4。;②支架置入后,瘤颈部所对应的血管段内,血液涡流明显减少,流线趋于平直;③单纯弹簧圈致密填塞后瘤颈部平均WSS为11．55Pa,支架置入后,该血管壁平均WSS为7．93Pa,下降31．3％。结论支架置入治疗前交通动脉宽颈动脉瘤可明显改变载瘤动脉的形态,并改变局部载瘤动脉的血流动力学,降低动脉瘤的WSS。     

Preliminary Evaluation of Hemodynamic Effects of Fontan Palliation on Renal Artery Using Computational Fluid Dynamics

Background: The assessment of renal function is important to the prognosis of patients needing Fontan palliation due to the reconstructed compromised circulation. To know the relationship between the kidney perfusion and hemodynamic characteristics during surgical design could reduce the risk of acute kidney injury (AKI) and the postoperative complications. However, the issue is still unsolved because the current clinical evaluation methods are unable to predict the hemodynamic changes in renal artery (RA). Methods: We reconstructed a three-dimensional (3D) vascular model of a patient requiring Fontan palliation. The technique of computational fluid dynamics (CFD) was utilized to explore the changes of RA hemodynamics under different possible blood flow rates. The relationship between the kidney perfusion and hemodynamic characteristics was investigated. Results: The calculated results indicated the declined tendency of the pressure and pressure drop as the flow rate decreased. When the flow rate decreased to two-thirds of its baseline, both the pressure of left renal artery (LRA) and the pressure of right renal artery (RRA) dipped below 50%, and the pressure of RRA fell more quickly than that of LRA. Uneven distribution of WSS was observed on the trunk of RA, and the lowest WSS was found at the distal of RA. The average WSS in RA dropped to around 50% as the flow rate reached one-third of its baseline. Conclusions: As a promising approach, CFD can be utilized to quantitatively evaluate the hemodynamic characteristics of RA and contribute to offsetting the drawbacks of clinical assessments of renal function, to help realize better prognosis for the patients with Fontan palliation.     

Redistribution of myocardial blood flow distal to a dynamic coronary arterial stenosis by sympathomimetic amines: Comparison of dopamine,dobutamine and isoproterenol

The effects of dopamine, dobutamine and isoproterenol on coronary hemodynamics, severity of stenosis, distal bed resistance and transmural myocardial perfusion gradients with radioactive microspheres were studied in dogs with a mild obstruction of the left circumflex coronary artery anesthetized with morphine-chloralose. Changes in transmural blood flow were related to the ratio of the diastolic aortic pressure-time Index to tension-time index (DPTI/TTI) and the ratio of the distal diastolic coronary pressure-time index to tension-time index (DDPT1/TTI). At doses of 5 gmg/kg per min, dopamine had no significant effect on DPTI/TTI, DDPTI/TTI or endocardial/epicardial flow ratio; however, dobutamine produced a slight decrease in this flow ratio and in DDPTI/TTI. At doses of 10 gmg/kg per min, both drugs produced a significant (p <0.05) reduction in diastolic coronary pressure distal to the stenosis, DDPTI/TTI and endocardial/epicardial flow ratio without change in DPTI/TTI. In comparison, isoproterenol (0.01 and 0.05 gmg/kg per min) produced dose-related decreases in endocardial/epicardial flow ratio, DDPTI/TTI and DPTI/TTI. During infusion of each sympathomimetic agent, there was a corresponding reduction in distal bed vascular resistance but a concomitant increase in stenosis resistance.The results also show that dopamine and dobutamine, as well as isoproterenol, are capable of producing a maldistribution of coronary blood flow distal to a mild coronary arterial stenosis and that such a redistribution of flow is dependent on dose, reduction of the distal diastolic coronary pressure-time index and decrease in DDPTI/TTI. It Is further concluded that hemodynamic changes distal to a coronary arterial stenosis seriously jeopardize the usefulness of DPTI/TTI; however, DDPTI/TTI can be used to predict drug effects on the endocardial/epicardial flow ratio in an ischemie area. This study demonstrates that “fixed” stenoses can undergo dynamic processes and sympathomlmetic amines increase the resistance to flow through a stenotic coronary artery in the nonfailing heart.     

Evolution of regional ischemia distal to a proximal coronary stenosis: Self-propagation of ischemia

The temporal evolution of myocardial ischemia was studied in open chest dogs at constant preload, afterload and heart rate. In one group of animals, a variable circumflex arterial stenosis was used to maintain constant distal circumflex arterial hypotension (40 to 50 mm Hg). During a 3 hour period of stenosis, flow in the subendocardial fourth of the ischemic ventricular wall decreased from 0.22 to 0.09 ml/g per min (P < 0.02), whereas subepicardial flow was not significantly changed. Local vascular resistance, therefore, doubled in the most ischemic area of myocardium. In a second group of animals in which proximal coronary stenosis was held constant and pressure varied, an ischemia-mediated increase in local vascular resistance was also demonstrated. In addition, a reciprocal relation was observed between changes in flow in the left anterior descending coronary region and changes in collateral flow to the region of the circumflex artery. A coronary steal mechanism and an ischemiamediated resistance increase may be two means by which ischemia is self-propagating.     

The thromboxane A2 mimetic U46619 worsens canine myocardial hypoperfusion during exercise in the presence of a coronary artery stenosis.

OBJECTIVE: The aim was to test the hypothesis that thromboxane A2 can cause vasoconstriction of coronary resistance vessels during exercise in hypoperfused regions of myocardium distal to an arterial stenosis. METHODS: Eight adult mongrel dogs were studied. Chronically instrumented animals with a left circumflex coronary artery Doppler flow meter, hydraulic occluder, and indwelling catheter underwent treadmill exercise at heart rates of 190-200 beats.min-1. Myocardial blood flow was measured with microspheres during unimpeded arterial inflow and in the presence of a coronary stenosis which decreased distal pressure to 42-45 mm Hg. Measurements were repeated during infusion of the thromboxane A2 analogue, U46619. RESULTS: When the occluder was partially inflated to produce a stenosis, blood flow in the region perfused by the stenotic artery was 58 (SEM 6)% of flow in the normally perfused region (p less than 0.01). U46619 (0.01 microgram.kg-1.min-1) caused a further 21 (7)% decrease in blood flow in the region perfused by the stenotic artery (p less than 0.05). The vasoconstriction produced by U46619 was uniform across the left ventricular wall from epicardium to endocardium. U46619 did not significantly decrease myocardial blood flow in the absence of a coronary stenosis. CONCLUSIONS: Even during hypoperfusion produced by a flow limiting arterial stenosis, the coronary resistance vessels remain responsive to the vasoconstrictor effect of thromboxane A2. Liberation of thromboxane A2 during platelet activation at the site of a proximal coronary stenosis may worsen myocardial hypoperfusion by causing vasoconstriction of the distal resistance vessels.     

Boundary Conditions in Simulation of Stenosed Coronary Arteries

A powerful alternative means to studying hemodynamics in diseased or healthy coronary arteries can be achieved by providing a numerical model in which blood flow can be virtually simulated, for instance, using the computational fluid dynamics (CFD) method. In fact, it is well documented that CFD allows reliable physiological blood flow simulation and measurements of flow parameters. A requisite for obtaining reliable results from coronary CFD is to use exact anatomical models and realistic boundary conditions. To date, in almost all of the modeling studies on hemodynamics of stenosed coronary arteries, a velocity based boundary conditions has been assigned. The objective of this study is to show that inlet velocity actually depends on the degree of stenosis and thus for severe constriction in coronary artery, a velocity based boundary conditions cannot be realistic. We then prove that regardless of severity of stenosis in coronary arteries, the upstream pressure, systemic pressure, is always constant, thus, should be used as boundary conditions instead. The two sets of boundary conditions are implemented to demonstrate the robustness of each in modeling of stenosed coronary artery in a CFD study. These boundary conditions are applied in a stenosed cylindrical pipe including three categories of symmetrical stenosis (mild, moderate and severe stenosis starting from 15 to 95% diameter reduction) for steady state and pulsatile flow. Results strongly indicate that inlet velocity boundary conditions are no longer valid when effective diameter in stenosis goes below ~2.8 mm (a healthy diameter is considered 3.2 mm) which corresponds to 10–15% diameter reduction. Further work will determine the effect of flow reduction on the oxygen tension in blood to better define conditions for clinical symptoms such as angina.     

Coronary CT angiography: Beyond morphological stenosis analysis

Rapid technological developments in computed tomography (CT) imaging technique have made coronary CT angiography an attractive imaging tool in the detection of coronary artery disease. Despite visualization of excellent anatomical details of the coronary lumen changes, coronary CT angiography does not provide hemodynamic changes caused by presence of plaques. Computational fluid dynamics (CFD) is a widely used method in the mechanical engineering field to solve complex problems through analysing fluid flow, heat transfer and associated phenomena by using computer simulations. In recent years, CFD is increasingly used in biomedical research due to high performance hardware and software. CFD techniques have been used to study cardiovascular hemodynamics through simulation tools to assist in predicting the behaviour of circulatory blood flow inside the human body. Blood flow plays a key role in the localization and progression of coronary artery disease. CFD simulation based on 3D luminal reconstructions can be used to analyse the local flow fields and flow profiling due to changes of vascular geometry, thus, identifying risk factors for development of coronary artery disease. The purpose of this article is to provide an overview of the coronary CT-derived CFD applications in coronary artery disease.