心脏病是严重威胁人类健康的第一杀手，虽然治疗技术取得了长足的发展，但是人们对心脏更深层次上的认识以及心脏病的预防和治疗远未达到理想水平。为了更深入研究目前靠生理实验手段无法有效解释的基因变异导致Timothy综合征(TS)并诱发室速、室/房颤发病机制的问题，本课题拟利用计算模型仿真和假设分析的优势，来开展“基于多尺度心脏计算模型的Timothy综合征发病机制研究”，首先基于TS基因变异、离子通道功能改变、自主神经调控作用和临床心电图等相关生理实验数据，建立从亚细胞到体表心电图的多尺度计算模型，然后通过模拟仿真结果来分析TS基因变异对细胞动作电位、兴奋传导能力、单向传导阻滞时间窗、心电图等电生理特征的影响，来研究和解释TS基因变异产生致命性心律失常的发病机制。本研究将为TS病人的临床治疗和抗心律失常药物筛选提供理论和技术支撑。

Cardiovascular diseases are the world’s biggest killers. Although much progress has been made in medical technology for cardiac treatment, understanding mechanisms underlying heart function and the prevention and treatment of heart disease remain incomplete. To further study on these issues, potential mechanistic links between gene mutations and the Timothy syndrome (TS), ventricular tachycardia and ventricular/atrial fibrillation，which cannot be effectively explained by physiological experiments, our group takes advantage of computational simulation and hypothetical analysis to carry out this project “Research on the Pathogenesis of Timothy Syndrome Based on Multi-scale Computational Model of the Human Heart”. Firstly, a multi-scale computational model from subcellular proteins to surface electrocardiogram is established based on experimental data on the genetic variation of Timothy syndrome, changes in ion channel function, autonomic nervous regulation and clinical electrocardiogram; Secondly, we investigate the effects of gene mutations linked to Timothy syndrome on electrophysiological characteristics, such as action potential, excitation conduction ability, vulnerable window for unidirectional conduction block and simulated electrocardiogram; Finally, these potential mechanisms underlying Timothy syndrome and arrhythmias are explained. This study will provide a preliminary theoretical basis for clinical treatment and antiarrhythmic drug screening in patients with Timothy syndrome.