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心律失常是当前生物物理交叉学科中发展得比较成熟的一个分支, 在实验和理论方面均取得了丰硕的成果. 近年来, 随着实验数据的积累, 人们在多个尺度上发现了更丰富多样的心律失常诱因, 这对物理学的研究提出了新的需求和挑战. 因此, 心肌系统的多尺度建模、计算和动力学分析是心律失常领域进一步发展的关键. 本文旨在对这个课题进行一个阶段性的回顾, 扼要介绍心肌多尺度建模的基本理念和方法, 并以尺度为脉络, 介绍近年来在心律失常机制理论方面取得的若干重要成果. 现有成果表明, 非线性动力学、斑图动力学和统计物理对心律失常的基本认识和理论的发展具有重要的意义. 未来的研究应在拓展模型尺度(向更微观和宏观方向拓展模型), 解决心律失常基础动力学问题(如非均匀系统的稳定性、斑图的相变理论), 以及解决更复杂而基本的生理医学问题(如心率变异、人群心律失常发生概率风险的评估)等方面继续深入探索.Biological systems are complex systems that are regulated on multiple scales, with dynamics ranging from random molecular fluctuations to spatiotemporal wave dynamics and periodic oscillations. To understand the underlying mechanisms and link the dynamics on a molecular scale to those on a tissue scale and an organ scale, the research approaches to integrating computer modeling and simulation, nonlinear dynamics, and experimental and clinical data have been widely used. In this article, we review how these approaches have been used to investigate the multiscale cardiac excitation dynamics, particularly the genesis of cardiac arrhythmias that can lead to sudden death. The specific topics covered in this review are as follows: i) mechanisms of formation of intracellular calcium sparks and waves on a subcellular scale, which can be described by the stochastic transitions between the two stable states of a bistable system and the second order phase transition, respectively; ii) mechanisms of triggered activities on a cellular scale resulting from transmembrane voltage and intracellular calcium cycling and their coupling, some of which can be well described by the bifurcation theories of the nonlinear dynamical system; iii) mechanisms for the genesis of arrhythmias on a tissue scale induced by the triggered activities, which can be regarded as dynamical instability-induced pattern formation in heterogeneous excitable media; and iv) manifestations of the excitation dynamics and transitions in the whole heart (on an organ scale) in electrocardiogram to bridge the spatiotemporal wave dynamics to clinical observations. These results indicate that nonlinear dynamics, pattern formation, and statistical physics are the fundamental components in establishing a theoretical framework for understanding cardiac arrhythmias.
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临床与实验数据 建模与计算 动力学理论 微观 钙火花[59]
长钙火花[53]
钙波[76]RyR随机模型[21]
CRU网络模型[54,78]钙火花的势阱逃逸理论[62,68,69]
钙波的相变理论[76,79,80,121]细胞 钙电耦合的EAD
振荡[108,109]
DAD的随机性[112]钙电耦合细致细胞
模型[23–25]EAD的霍普夫分岔理论[96,100,104]
DAD的Kramers随机跃迁
理论[117]组织 “冲动+基质”致
心律失常[41,42,89]非均匀可激发
介质[154,156]早搏的动力学稳定性理论[156];
螺旋波的形成、稳定性、
调控[137,142,143,158]器官 R-on-T发展为
TdP[87]全心室多尺度
模型[51,160]TdP的“R-on-T”机制理论[55,158] -
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