心肌桥冠状动脉血液动力学数值模拟与体外模拟装置研制
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摘要
大量研究表明心肌桥对冠状动脉形态学和血流动力学产生一定的影响,其近心端为动脉硬化高发区之一。目前有关心肌桥近心端血液动力学异常与近心端易发动脉粥样硬化产生之间关系的研究报道较为少见。
由于血流动力学因素在动脉粥样硬化的发生和发展过程中起着重要的作用,深入地研究由心肌桥造成的冠状动脉血流动力学环境的改变,研究这种变化与其近心端动脉粥样硬化病变之间的关系,对冠脉粥样硬化发病机理的认识具有重要的意义,对于心肌桥的治疗具有潜在的临床价值。
本文以心肌桥冠状动脉近心端这一易发动脉粥样硬化区域作为切入点,分别从数值模拟和实验模拟出发,根据心肌桥主要特点建立心肌桥血液动力学数值仿真模型以及体外模拟装置,研究、分析心肌桥易诱发动脉粥样硬化的血液动力学机制。
数值模拟
(1)建立轻度狭窄的心肌桥模型,线化的Navier-Stokes血液动力学方程。根据血流脉动周期变化的特点,采用谐波叠加的方法导出虚宗量系数的压强方程及有关血液动力学指标数学表达式。数值求解压强方程,最终得到各血液动力学指标：压强P、压强梯度dP/dz、管壁剪切应力WSS及脉动振荡因子OSI。采用这些指标进行了以下工作：
a.对正常冠状动脉血液动力学和心肌桥冠状动脉血液动力学进行了比较；
b.对血管顺应性影响心肌桥冠状动脉血液动力学进行了比较；
c.对心率影响心肌桥冠状动脉血液动力学进行了比较。
(2)构建一般心肌桥冠状动脉模型,心肌桥血液动力学一维管流基本方程。借鉴“边界层流动”的Karman动量积分方程求解方法,得出一维管流方程中的粘性摩擦。用差分方法数值求解。
a.对正常冠状动脉血液动力学和心肌桥冠状动脉血液动力学进行了比较；
b.对心肌桥近心端和远心端血液动力学进行了比较；
c.分析了狭窄程度以及有两段心肌桥对心肌桥血液动力学的影响。
所得结果表明,心肌桥冠状动脉血液动力学和正常冠状动脉血液动力学有较大的区别；在心肌桥的近心端,若干血液动力学指标异常,压强、壁面切应力、切应力梯度、切应力梯度震荡数的变化比其它部位剧烈。这为心肌桥近心端易诱发粥样硬化从数值仿真角度提供了血液动力学机制的解释。
体外模拟装置研制和实验模拟
(1)研制了一个集模拟血流循环及参数测量模块、心肌桥模块和园管流动腔内皮细胞培养模块等功能模块于一体的心肌桥冠状动脉血液动力学体外模拟装置。
该模拟装置建立了接近人体生理条件的心肌桥冠状动脉血流动力学环境,参数可控制,为深入研究心肌桥造成的壁冠状动脉血流动力学环境的改变与其近心端动脉粥样硬化病变之间的关系,探索动脉粥样硬化形成机理提供了实验环境和研究手段。
(2)心肌桥冠状动脉血液动力学体外模拟装置功能测评
模拟装置功能测评结果表明：各功能系统运行状态良好、性能稳定,实验条件控制方便,能较好模拟心肌桥冠状动脉血液循环的流场和相应的应力环境。
(3)模拟装置的体外模拟实验
a.利用心肌桥壁冠状动脉血流动力学体外模拟装置进行血流动力学模拟实验。所得结果表明,心肌桥的存在全面影响壁冠状动脉内应力(切应力、正应力与周向应力)平均值与应力波动值,从现有的模拟实验结果来看,心肌桥压迫壁冠状动脉程度愈甚,壁冠状动脉近心端应力平均值及应力震荡愈大,且近心端应力震荡较远心端剧烈,联系到心肌桥壁冠状动脉近心端高发动脉粥样硬化的现象,有理由推断近心端应力水平及应力震荡的增大与动脉粥样硬化有因果关系。
b.在园管流动腔内皮细胞培养模块中进行了内皮细胞培养预实验。
(1)建立心肌桥血液动力学数值仿真模型,对心肌桥冠状动脉的各项血液动力学指标进行了计算,首次从数值模拟角度阐述了心肌桥冠状动脉血液动力学异常与近心端易诱发动脉粥样硬化之间的内在联系。
(2)研制心肌桥冠状动脉血液动力学体外模拟装置,实现了心肌桥冠状动脉近心端与远心端切应力、正应力、周向应力的模拟；进行体外模拟实验,从实验模拟角度分析了心肌桥冠状动脉血液动力学异常与近心端易诱发动脉粥样硬化的内在关联。
(3)研制园管流动腔内皮细胞培养装置并成功地进行了内皮细胞培养预实验,为进一步在细胞水平探索心肌桥易诱发动脉粥样硬化的血液动力学机制提供了技术手段。内皮细胞培养装置不仅用于心肌桥动脉粥样硬化研究,也可为与内皮细胞有关的心血管疾病的研究提供实验装置与研究手段。
A large number of studies had shown that myocardial bridge has certain impacts on morphology of coronary artery and haemodynamics, and the proximal is one of the areas with high incidence of atherosclerosis. Nowadays there were a few reports about the relationships between abnormal haemodynamics of proximal and proximal atherosclerosis-prone.
As haemodynamic factors play an important part in the occurrence and development of atherosclerosis, it is of significance to understand pathogenesis of atherosclerosis by extensive studies on the mural coronary artery haemodynamics changing caused by myocardial bridge and studies on the relationships between the changing and proximal atherosclerosis, which has a potential clinical value on treatment of myocardial bridge.
In this paper, atherosclerosis-prone proximal is regarded as a point of view, and then we set up simulation of haemodynamic model and vitro simulative device from numerical simulation and experimental simulations according to the main feature of myocardial bridge, with which we study and analyze the haemodynamic mechanism of atherosclerosis caused by myocardial bridge.
Main works
Numerical simulation
(1) Establish mild stenosis myocardial bridge model and linear Navier-Stokes haemodunamic equation. Pressure equation of virtual variables coefficient and mathematical expression of haemodynamic indexes are derived by harmonic superposition according to the characteristic of blood flow pulsation cycle. Solve the pressure equation, and find the haemodynamic indexes:pressure P, pressure gradient dP/dz, wall shear stress WSS and oscillation shear index OSI. We use these indexes to work:
a. Compare haemodynamics of normal coronary artery with myocardial bridge coronary artery;
b. Compare hemodynamics of myocardial bridge coronary artery which affected by vascular compliance;
c. Compare hemodynamics of myocardial bridge coronary artery which affected by heart rate.
(2) Establish an ordinary myocardial bridge model and myocardial bridge haemodynamic basic equations of one-dimensional pipe flow. Viscous friction of equations of one-dimensional pipe flow is got from the solution of "Boundary layer flow" Karman momentum integral equation. Solve equation with typical line.
a. Compare haemodynamics of normal coronary artery with myocardial bridge coronary artery;
b. Compare haemodynamics of myocardial bridge proximal with distal;
c. Analyze the impacts on haemodynamics respectively by the degree stenosis and two myocardial bridges.
The result shows that there are great differences between myocardial bridge coronary artery haemodynamics and normal one; there are several abnormal haemodynamic indexes beneath myocardial bridge and proximal, whose pressure, wall shear stress, wall shear stress gradient, gradient oscillatory number change greater than other areas. It offers a haemodynamic mechanism explanation for myocardial bridge proximal easily inducing atherosclerosis from numerical simulation.
Development of vitro simulative device and simulative experiment
(1) Develop a coronary artery-myocardial bridge haemodynamic vitro simulative device assembled with blood flow module, parameters measurement module, myocardial bridge module, flexible tubulose cells culture module.
This device provides a myocardial bridge coronary artery haemodynamic environment approached to human physiological condition, whose parameters are controllable. It provides a experimental condition and investigative measurements for studying the relationship between haemodynamic parameters changing of mural coronary artery cased by myocardial bridge and proximal atherosclerosis and exploring mechanism of atherosclerosis.
(2) Performance evolution of coronary artery-myocardial bridge haemodynamic vitro simulative device
Performance evolution of simulative device proves that every functional system is running in a good condition, function is stable and experimental conditions are easily controlled. It could perfectly simulate three-dimensional flow field and relevant stress environments when blood flow circulates in myocardial bridge coronary artery.
(3) Vitro simulative experiment of simulative device
a. Results from vitro simulative experiment with myocardial bridge mural coronary artery haemodynamic simulative device show that the existence of myocardial bridge totally impacts on the average stress (wall shear stress, direct stress and circumferential stress) and undulating stress in the mural coronary artery. From the recent results, the more serious the myocardial bridge is, the higher the average stress and stress oscillatory number are at proximal in mural coronary artery, and even proximal is greater than distal. Contacting with the phenomenon that the proximal is atherosclerosis-prone, we have reasons to conclude there is certain relationships between stress level, increasing oscillatory stress and atherosclerosis.
b. Take endothelial cells culture preliminary experiment in the flexible tubulose cells culture module.
Characteristic and innovation
(1) Establish myocardial bridge haemodynamic numerical simulative model and calculate haemodynamic indexes of myocardial bridge, explain the relationships between abnormal haemodynamics and proximal atherosclerosis-prone from numerical simulation for the first time.
(2) Develop a myocardial bridge coronary artery haemodynamic vitro simulative device, which simulate the wall shear stress, direct stress, circumferential stress of proximal and distal; complete a vitro simulative experiment, and analyze the internal connections between abnormal haemodynamics of myocardial bridge coronary artery and proximal atherosclerosis-prone.
(3) Develop the flexible tubulose endothelial cells culture device, with which we take an endothelial cells culture preliminary experiment successfully. It provides a further technology to explore the haemodynamic mechanism of atherosclerosis caused by myocardial bridge from cells. The endothelial cells culture device is not only used to study atherosclerosis caused by myocardial bridge, but also be used as the experimental measurement and device to study cardiovascular disease related to cells.
由于血流动力学因素在动脉粥样硬化的发生和发展过程中起着重要的作用,深入地研究由心肌桥造成的冠状动脉血流动力学环境的改变,研究这种变化与其近心端动脉粥样硬化病变之间的关系,对冠脉粥样硬化发病机理的认识具有重要的意义,对于心肌桥的治疗具有潜在的临床价值。
本文以心肌桥冠状动脉近心端这一易发动脉粥样硬化区域作为切入点,分别从数值模拟和实验模拟出发,根据心肌桥主要特点建立心肌桥血液动力学数值仿真模型以及体外模拟装置,研究、分析心肌桥易诱发动脉粥样硬化的血液动力学机制。
数值模拟
(1)建立轻度狭窄的心肌桥模型,线化的Navier-Stokes血液动力学方程。根据血流脉动周期变化的特点,采用谐波叠加的方法导出虚宗量系数的压强方程及有关血液动力学指标数学表达式。数值求解压强方程,最终得到各血液动力学指标：压强P、压强梯度dP/dz、管壁剪切应力WSS及脉动振荡因子OSI。采用这些指标进行了以下工作：
a.对正常冠状动脉血液动力学和心肌桥冠状动脉血液动力学进行了比较；
b.对血管顺应性影响心肌桥冠状动脉血液动力学进行了比较；
c.对心率影响心肌桥冠状动脉血液动力学进行了比较。
(2)构建一般心肌桥冠状动脉模型,心肌桥血液动力学一维管流基本方程。借鉴“边界层流动”的Karman动量积分方程求解方法,得出一维管流方程中的粘性摩擦。用差分方法数值求解。
a.对正常冠状动脉血液动力学和心肌桥冠状动脉血液动力学进行了比较；
b.对心肌桥近心端和远心端血液动力学进行了比较；
c.分析了狭窄程度以及有两段心肌桥对心肌桥血液动力学的影响。
所得结果表明,心肌桥冠状动脉血液动力学和正常冠状动脉血液动力学有较大的区别；在心肌桥的近心端,若干血液动力学指标异常,压强、壁面切应力、切应力梯度、切应力梯度震荡数的变化比其它部位剧烈。这为心肌桥近心端易诱发粥样硬化从数值仿真角度提供了血液动力学机制的解释。
体外模拟装置研制和实验模拟
(1)研制了一个集模拟血流循环及参数测量模块、心肌桥模块和园管流动腔内皮细胞培养模块等功能模块于一体的心肌桥冠状动脉血液动力学体外模拟装置。
该模拟装置建立了接近人体生理条件的心肌桥冠状动脉血流动力学环境,参数可控制,为深入研究心肌桥造成的壁冠状动脉血流动力学环境的改变与其近心端动脉粥样硬化病变之间的关系,探索动脉粥样硬化形成机理提供了实验环境和研究手段。
(2)心肌桥冠状动脉血液动力学体外模拟装置功能测评
模拟装置功能测评结果表明：各功能系统运行状态良好、性能稳定,实验条件控制方便,能较好模拟心肌桥冠状动脉血液循环的流场和相应的应力环境。
(3)模拟装置的体外模拟实验
a.利用心肌桥壁冠状动脉血流动力学体外模拟装置进行血流动力学模拟实验。所得结果表明,心肌桥的存在全面影响壁冠状动脉内应力(切应力、正应力与周向应力)平均值与应力波动值,从现有的模拟实验结果来看,心肌桥压迫壁冠状动脉程度愈甚,壁冠状动脉近心端应力平均值及应力震荡愈大,且近心端应力震荡较远心端剧烈,联系到心肌桥壁冠状动脉近心端高发动脉粥样硬化的现象,有理由推断近心端应力水平及应力震荡的增大与动脉粥样硬化有因果关系。
b.在园管流动腔内皮细胞培养模块中进行了内皮细胞培养预实验。
(1)建立心肌桥血液动力学数值仿真模型,对心肌桥冠状动脉的各项血液动力学指标进行了计算,首次从数值模拟角度阐述了心肌桥冠状动脉血液动力学异常与近心端易诱发动脉粥样硬化之间的内在联系。
(2)研制心肌桥冠状动脉血液动力学体外模拟装置,实现了心肌桥冠状动脉近心端与远心端切应力、正应力、周向应力的模拟；进行体外模拟实验,从实验模拟角度分析了心肌桥冠状动脉血液动力学异常与近心端易诱发动脉粥样硬化的内在关联。
(3)研制园管流动腔内皮细胞培养装置并成功地进行了内皮细胞培养预实验,为进一步在细胞水平探索心肌桥易诱发动脉粥样硬化的血液动力学机制提供了技术手段。内皮细胞培养装置不仅用于心肌桥动脉粥样硬化研究,也可为与内皮细胞有关的心血管疾病的研究提供实验装置与研究手段。
A large number of studies had shown that myocardial bridge has certain impacts on morphology of coronary artery and haemodynamics, and the proximal is one of the areas with high incidence of atherosclerosis. Nowadays there were a few reports about the relationships between abnormal haemodynamics of proximal and proximal atherosclerosis-prone.
As haemodynamic factors play an important part in the occurrence and development of atherosclerosis, it is of significance to understand pathogenesis of atherosclerosis by extensive studies on the mural coronary artery haemodynamics changing caused by myocardial bridge and studies on the relationships between the changing and proximal atherosclerosis, which has a potential clinical value on treatment of myocardial bridge.
In this paper, atherosclerosis-prone proximal is regarded as a point of view, and then we set up simulation of haemodynamic model and vitro simulative device from numerical simulation and experimental simulations according to the main feature of myocardial bridge, with which we study and analyze the haemodynamic mechanism of atherosclerosis caused by myocardial bridge.
Main works
Numerical simulation
(1) Establish mild stenosis myocardial bridge model and linear Navier-Stokes haemodunamic equation. Pressure equation of virtual variables coefficient and mathematical expression of haemodynamic indexes are derived by harmonic superposition according to the characteristic of blood flow pulsation cycle. Solve the pressure equation, and find the haemodynamic indexes:pressure P, pressure gradient dP/dz, wall shear stress WSS and oscillation shear index OSI. We use these indexes to work:
a. Compare haemodynamics of normal coronary artery with myocardial bridge coronary artery;
b. Compare hemodynamics of myocardial bridge coronary artery which affected by vascular compliance;
c. Compare hemodynamics of myocardial bridge coronary artery which affected by heart rate.
(2) Establish an ordinary myocardial bridge model and myocardial bridge haemodynamic basic equations of one-dimensional pipe flow. Viscous friction of equations of one-dimensional pipe flow is got from the solution of "Boundary layer flow" Karman momentum integral equation. Solve equation with typical line.
a. Compare haemodynamics of normal coronary artery with myocardial bridge coronary artery;
b. Compare haemodynamics of myocardial bridge proximal with distal;
c. Analyze the impacts on haemodynamics respectively by the degree stenosis and two myocardial bridges.
The result shows that there are great differences between myocardial bridge coronary artery haemodynamics and normal one; there are several abnormal haemodynamic indexes beneath myocardial bridge and proximal, whose pressure, wall shear stress, wall shear stress gradient, gradient oscillatory number change greater than other areas. It offers a haemodynamic mechanism explanation for myocardial bridge proximal easily inducing atherosclerosis from numerical simulation.
Development of vitro simulative device and simulative experiment
(1) Develop a coronary artery-myocardial bridge haemodynamic vitro simulative device assembled with blood flow module, parameters measurement module, myocardial bridge module, flexible tubulose cells culture module.
This device provides a myocardial bridge coronary artery haemodynamic environment approached to human physiological condition, whose parameters are controllable. It provides a experimental condition and investigative measurements for studying the relationship between haemodynamic parameters changing of mural coronary artery cased by myocardial bridge and proximal atherosclerosis and exploring mechanism of atherosclerosis.
(2) Performance evolution of coronary artery-myocardial bridge haemodynamic vitro simulative device
Performance evolution of simulative device proves that every functional system is running in a good condition, function is stable and experimental conditions are easily controlled. It could perfectly simulate three-dimensional flow field and relevant stress environments when blood flow circulates in myocardial bridge coronary artery.
(3) Vitro simulative experiment of simulative device
a. Results from vitro simulative experiment with myocardial bridge mural coronary artery haemodynamic simulative device show that the existence of myocardial bridge totally impacts on the average stress (wall shear stress, direct stress and circumferential stress) and undulating stress in the mural coronary artery. From the recent results, the more serious the myocardial bridge is, the higher the average stress and stress oscillatory number are at proximal in mural coronary artery, and even proximal is greater than distal. Contacting with the phenomenon that the proximal is atherosclerosis-prone, we have reasons to conclude there is certain relationships between stress level, increasing oscillatory stress and atherosclerosis.
b. Take endothelial cells culture preliminary experiment in the flexible tubulose cells culture module.
Characteristic and innovation
(1) Establish myocardial bridge haemodynamic numerical simulative model and calculate haemodynamic indexes of myocardial bridge, explain the relationships between abnormal haemodynamics and proximal atherosclerosis-prone from numerical simulation for the first time.
(2) Develop a myocardial bridge coronary artery haemodynamic vitro simulative device, which simulate the wall shear stress, direct stress, circumferential stress of proximal and distal; complete a vitro simulative experiment, and analyze the internal connections between abnormal haemodynamics of myocardial bridge coronary artery and proximal atherosclerosis-prone.
(3) Develop the flexible tubulose endothelial cells culture device, with which we take an endothelial cells culture preliminary experiment successfully. It provides a further technology to explore the haemodynamic mechanism of atherosclerosis caused by myocardial bridge from cells. The endothelial cells culture device is not only used to study atherosclerosis caused by myocardial bridge, but also be used as the experimental measurement and device to study cardiovascular disease related to cells.
引文
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