Acute myocardial ischaemia caused by coronary artery disease is one of the main causes of sudden cardiac death. Even though sodium current blockers are used as anti-arrhythmic drugs, decreased sodium current availability, also caused by mutations, has been shown to increase arrhythmic risk in ischaemic patients. The mechanisms are still unclear. Our goal is to exploit perfect control and data transparency of over 300 high-performance computing simulations to investigate arrhythmia mechanisms in acute myocardial ischaemia with variable sodium current availability. The human anatomically based torso-biventricular electrophysiological model used includes representation of realistic ventricular anatomy and fibre architecture, as well as ionic to electrocardiographic properties. Simulations show that reduced sodium current availability increased arrhythmic risk in acute regional ischaemia due to both electrophysiological (increased dispersion of refractoriness across the ischaemic border zone) and anatomical factors (conduction block from the thin right ventricle to thick left ventricle). The asymmetric ventricular anatomy caused high arrhythmic risk specifically for ectopic stimuli originating from the right ventricle and ventricular base. Increased sodium current availability was ineffective in reducing arrhythmic risk for septo-basal ectopic excitation. Human-based multiscale modelling and simulations reveal key electrophysiological and anatomical factors determining arrhythmic risk in acute ischaemia with variable sodium current availability.

冠状动脉疾病引起的急性心肌缺血是心源性猝死的主要原因之一。尽管钠电流阻滞剂被用作抗心律失常药物，但同样由突变引起的钠电流可用性降低已被证明会增加缺血性患者的心律失常风险。机制仍不清楚。我们的目标是利用 300 多个高性能计算模拟的完美控制和数据透明度来研究具有可变钠电流可用性的急性心肌缺血的心律失常机制。使用的基于人体解剖学的躯干-双心室电生理模型包括真实心室解剖和纤维结构的表示，以及离子到心电图特性。模拟表明，由于电生理学（缺血边界区不应期的分散性增加）和解剖学因素（从薄的右心室到厚的左心室的传导阻滞），钠电流可用性降低会增加急性局部缺血的心律失常风险。不对称的心室解剖导致高心律失常风险，特别是来自右心室和心室基底的异位刺激。增加钠电流的可用性对于降低间隔基底节异位激发的心律失常风险无效。以人为基础的多尺度建模和模拟揭示了决定急性缺血性心律失常风险的关键电生理学和解剖学因素，其中钠电流可用性可变。