DataSheet1_A Novel In Silico Electromechanical Model of Human Ventricular Cardiomyocyte.PDF

Contractility has become one of the main readouts in computational and experimental studies on cardiomyocytes. Following this trend, we propose a novel mathematical model of human ventricular cardiomyocytes electromechanics, BPSLand, by coupling a recent human contractile element to the BPS2020 model of electrophysiology. BPSLand is the result of a hybrid optimization process and it reproduces all the electrophysiology experimental indices captured by its predecessor BPS2020, simultaneously enabling the simulation of realistic human active tension and its potential abnormalities. The transmural heterogeneity in both electrophysiology and contractility departments was simulated consistent with previous computational and in vitro studies. Furthermore, our model could capture delayed afterdepolarizations (DADs), early afterdepolarizations (EADs), and contraction abnormalities in terms of aftercontractions triggered by either drug action or special pacing modes. Finally, we further validated the mechanical results of the model against previous experimental and in silico studies, e.g., the contractility dependence on pacing rate. Adding a new level of applicability to the normative models of human cardiomyocytes, BPSLand represents a robust, fully-human in silico model with promising capabilities for translational cardiology.

收缩特性已成为心肌细胞计算与实验研究的核心观测指标之一。顺应这一研究趋势，我们将最新研发的人类收缩单元与电生理学模型BPS2020（BPS2020）相耦合，提出了一款全新的人类心室心肌细胞电-机械耦合数学模型BPSLand。
BPSLand是混合优化流程的产物，其不仅完整复现了前身模型BPS2020所能捕捉的全部电生理学实验指标，同时还能够模拟真实人类心肌的主动张力及其潜在异常状态。
本研究模拟了电生理学与收缩特性层面的跨壁异质性，该结果与此前的计算研究及体外（in vitro）实验结论一致。此外，本模型能够捕捉延迟后除极（delayed afterdepolarizations, DADs）、早期后除极（early afterdepolarizations, EADs），以及由药物作用或特殊起搏模式诱发的收缩后收缩异常。
最后，我们针对既往实验与计算机模拟（in silico）研究验证了该模型的力学结果，例如收缩性对起搏频率的依赖性。作为人类心肌细胞标准化模型的适用性拓展，BPSLand是一款稳健的全人类源计算机模拟模型，在转化心脏病学领域具备良好的应用潜力。