基于心电研究进展完善心电模型构建和心律失常研究的策略

Strategies to Improve Cardiac Electrical Modeling and Arrhythmic Evaluation Based on the Progress in Electrophysiological Study

心律失常是一类严重威胁人类生命安全的心血管疾病,其机制复杂,临床治疗亟待改进。当前虚拟电生理仿真模型整合离子通道电生理特性、动作电位、体表心动图等基础研究数据,对心电活动和心律失常机制的阐释有了长足的进步,但与真实人体心电活动仍存在一定差异。本文结合基础与临床最新研究进展,提出将离子通道β亚基、细胞器和亚细胞结构等调节心电活动的数据以及基于人类iPS衍生的心脏类器官获取的心电数据纳入心电模型构建的策略,从微观和宏观多尺度更新、完善和验证虚拟心脏电生理模型,并提出通过分子对接结合心电仿真模型筛选、评估靶向治疗心律失常药物的思路。

Arrhythmia is a common group of cardiovascular diseases that seriously threaten human health.The pathophysiological process and underlying mechanism of arrhythmia are complex and the clinical treatments are urgently needed to be improved.At present,the virtual heart electrophysiological simulation model was constructed by integrating a number of physiological and pathological data from the electrophysiological characteristics of ion channels,action potential,and body surface electrocardiogram(ECG),which makes great progress in the interpretation of electrophysiological activity and elucidating arrhythmia mechanism.However,there are still gaps between the simulated results from the electrophysiological models and the real human ECG activity.In this paper,we propose new strategies to update,improve and validate virtual heart electrophysiological models at the micro-and macro-scopes based on the progresses achieved recently in basic and clinical research.Incorporating the new electrophysiological regulation mechanisms,includingβsubunits of the ion channels,organelles,and subcellular structures,as well as electrophysiological data obtained from human-induced pluripotent stem cell-derived cardiac organoids into constructing electrophysiological models are highly valued.Moreover,we suggest strategies of combining molecular docking and electrophysiological simulation model in screening and evaluating the efficacy and safety of anti-arrhythmia drugs or compounds.