【作者】 潘清；

【导师】 宁钢民；

【作者基本信息】 浙江大学 ， 生物医学工程， 2013， 博士

【摘要】 心血管疾病是全球死亡率最高的疾病之一,其病理研究、早期预防和临床诊治是一项十分艰巨的工作。循环系统的数学模型可为心血管系统生理研究、心血管疾病的诊断和治疗提供了一种有效的辅助手段。多尺度循环系统数学模型主要研究系统、器官和组织层次循环系统模型耦合中的多物理场问题和多种维度建模技术问题。建立多尺度的循环系统数学模型,能够帮助定量分析循环系统各个层次上的生理和病理特性,提高心血管疾病的预防、诊断与治疗水平。本文的研究目标是通过对不同层次循环系统建模中关键技术问题的研究,建立多尺度循环系统数学模型。具体完成了以下工作：1、解决了循环系统多尺度模型研究中的关键技术问题,包括(1)仿真心率变异性的自主神经系统模型技术；(2)提高一维(One-Dimensional,1D)微循环模型仿真效率的数值计算技术；(3)整体循环系统与微循环系统的耦合技术。2、建立了整体循环系统与自主神经系统耦合模型,基于该模型提出了一种表征副交感神经活动的特异性参数。应用临床数据初步验证了该参数的有效性,并基于模型分析了其生理机制。3、建立了基于大鼠肠系膜实验数据的微循环系统1D模型,仿真了血流脉动性的衰减特性。基于模式动物实验验证了模型的有效性。应用该模型发现微血管的阻力与顺应性是血流脉动性衰减的主要原因。4、基于结构参数耦合了整体循环与微循环系统模型,仿真发现微循环结构性病变会改变整体血压水平。仿真结果还表明,高血压情况下外周血压脉动性降低,并影响微循环功能。在上述工作中,本文研究的创新点在于：1、提出了基于血管阻力及顺应性耦合的多尺度模型技术,有效地解决了整体循环与微循环系统模型结合的问题,为仿真研究血流动力学与功能特性的融合提供了有益的探索。2、基于结合自主神经调节机制的整体循环模型研究,提出了一种改进的心率减速能力参数,并借助模型阐明了算法改进的机理,为促进自主神经系统评价指标的临床应用提供了一种新的方法。3、提出了1D微循环系统建模中高效的数值计算方法,所建立的模型可系统地仿真血流脉动性衰减现象,改变了微循环血流脉动性衰减机制研究中缺乏技术手段的现状,为研究微循环中血流脉动性介导的机械信号转导过程提供了崭新的平台。本文所建立的多尺度循环系统数学模型为循环系统生理和病理研究提供了有效的定量研究技术平台,待其完善并应用后将有益于促进心血管疾病基础研究,提升国民心血管健康水平。更多还原

【Abstract】 Cardiovascular diseases (CVDs) are world-wide leading cause of death. The pathological research, early prevention, diagnosis and treatment of CVDs are great challenges. Mathematical models of the circulatory system provide an effective auxiliary means for the physiological research, diagnosis and treatment of CVDs. The multi-scale mathematical modeling of the circulatory system focuses on studying the nature of multiphysics and multi-dimensional modeling techniques in coupling multiple levels of circulatory systems, namely systematic, organic and tissular levels. The models are able to help study the pathophysiology of CVDs quantitatively in multiple scales, and improve the standard of the prevention, diagnosis and treatment of CVDs.This study aims to build a multi-scale mathematical model of the circulatory system based on the key technologies in multi-scale modeling. The main contributions of this study are summarized as follows:1. Key technologies in the multi-scale modeling of the circulatory system were developed, including (1) the autonomic nervous system (ANS) modeling technique which can simulate heart rate variability;(2) the numerical computing technique which can improve the simulation efficiency of one-dimensional (ID) microcirculatory model;(3) the coupling technique which can link the systemic and" microcirculatory systems.2. By the incorporation of the systemic circulatory model and the ANS model, an index which characterizes the parasympathetic activity was proposed. The index was verified by use of clinical data, and its physiological mechanism was interpreted by the model simulation.3. A ID microcirculation model was created based on the experimental data of rat mesentery and conducted to simulate the damping of blood flow pulsatility. The model was validated against the experiment of the model animal. With the help of the model, it is discovered that the vascular resistance and compliance are the major factors of the damping of blood flow pulsatility.4. The systemic and microcirculatory systems were coupled by structural parameters. The simulation of the coupled model explored that the structural alterations in the microcirculation affect the systemic blood pressure level. The simulation result also suggested that the peripheral blood pressure pulsatility under hypertension was reduced, and thus might result in the dysfuntion of microcirculation.The main innovations of the study are:1. A multi-scale modeling technique is proposed based on the coupling of vascular resistance and compliance. The technique solves the problem of incorporating the systemic and microcirculatory systems, and thus provides a beneficial approach in studying the fusion of hemodynamic and functional properties in the models.2. With the help of the incorporation of the systemic circulatory model and the ANS model, a modified deceleration capacity index of heart rate is produced, and its superiority is validated in mechanism. The model technique provides a novel method for promoting the clinical use of ANS index.3. The high-performance numerical methods for1D microcirculation model were developed to permit the simulation of the damping of blood flow pulsatility. The model fills the gap of methodology in the physiological study of the pulsatility damping mechanism, and provides a promising framework for the mechanotransduction research in the microcirculation.In conclusion, the multi-scale mathematical models of the circulatory system provide an effective technological platform for quantitative research. With the further improvement and utilization, the models are potential to benefit the fundamental cardiovascular research and improve the cardiovascular health of the public.更多还原