心律失常机制的建模仿真和理论研究  

Modeling,Simulation and Theoretical Study on Mechanisms of Cardiac Arrhythmias

作　　者：宋震 Song Zhen(Department of Mathematics and Theories,Peng Cheng Laboratory,Shenzhen 518066)

机构地区：[1]鹏城实验室数学和基础理论部,深圳518066

出　　处：《中国科学基金》2022年第2期245-254,共10页Bulletin of National Natural Science Foundation of China

基　　金：国家自然科学基金项目(82172067)资助。

摘　　要：心血管疾病是全球自然死亡的头号杀手。心律失常一直都是心血管疾病致死的一种主要形式。随着实验和临床数据的积累、非线性动力学的理论应用、计算机算法的优化和算力的提升,通过建立生理生化层面精细的心脏电生理数学模型,开展生理及病理条件下高性能计算仿真已成为探究心律失常机制的一种有效技术手段。本文简要介绍了造成心律失常的几种典型机制,回顾了心脏电生理建模仿真的发展过程并指出了目前面临的主要挑战,包括如何更系统深入地理解心律失常这一可激发介质上多尺度多物理态的复杂时空行为,如何运用电生理建模仿真辅助抗心律失常特效药物研发以及完善一般性药物的心脏安全评估。针对以上的挑战,本文提出如下研究建议:发展计算上可行的多尺度群体化心脏电生理数学模型;进行基于药物与蛋白/离子通道相互作用的虚拟抗心律失常药物靶点的筛查;建立一般性药物心脏毒性检测的虚拟仿真平台。通过深度结合实验和临床数据发展高性能多尺度群体化的心脏电生理虚拟仿真,有望进一步发掘多学科交叉的研究潜力,推动心脏病学发展。Cardiovascular disease is the leading cause of natural death worldwide.Cardiac arrhythmias have long been a major form of cardiovascular mortality.With the accumulation of experimental and clinical data,the theoretical application of nonlinear dynamics,the optimization of computer algorithms and the improvement on computing power,high-performance computing simulations under physiological and pathological conditions can be carried out by establishing a precise mathematical model of cardiac electrophysiology at the physiological and biochemical level.It has become an effective technical means to explore the mechanism of arrhythmia.This paper briefly introduces several typical mechanisms that cause arrhythmias,reviews the development of cardiac electrophysiological modeling and simulation,and points out the main challenges currently facing.These challenges include how to understand arrhythmia,a complex multi-scale spatiotemporal behavior on excitable medium,more systematically and insightfully;and how to use electrophysiological modeling and simulation to assist the development of specific antiarrhythmic drugs as well as improve the cardiac safety assessment of general drugs.In response to the above challenges,this paper proposes the following research topics:developing populations of multi-scale cardiac electrophysiological mathematical models that are computationally feasible,screening virtual antiarrhythmic drug targets based on drug-protein/ion channel interactions,establishing a general simulation platform for the detection of drug cardiotoxicity.By deeply combining experimental and clinical data to develop a high-performance multi-scale simulation platform of cardiac electrophysiology,it is expected to further explore the research potential for multi-disciplinary development of cardiology.

关 键 词：心血管疾病 心律失常 多尺度建模 虚拟药物靶点筛查 虚拟药物心脏毒性检测 

分 类 号：R541.7[医药卫生—心血管疾病]