Dataset for: Complex restitution behavior and reentry in a cardiac tissue model for neonatal mice

Spatio-temporal dynamics in cardiac tissue emerging from the coupling of individual cardiomyocytes underlie the heart’s normal rhythm as well as undesired and possibly life-threatening arrhythmias. While single cells and their transmembrane currents have been studied extensively, systematically investigating spatio-temporal dynamics is complicated by the non-trivial relationship between single-cell and emergent tissue properties. Mathematical models have been employed to bridge this gap and contribute to a deepened understanding of the onset, development and termination of arrhythmias. However, no such tissue-level model currently exists for neonatal mice. Here, we build on a recent single-cell model of neonatal mouse cardiomyocytes by Wang & Sobie (40) to predict properties that are commonly used to gauge arrhythmogenicity of cardiac substrates. We modify the model to yield well-defined behavior for common experimental protocols and construct a spatially extended version to study emergent tissue dynamics. We find a complex action potential duration (APD) restitution behavior characterized by a non-monotonic dependence on pacing frequency. Electrotonic coupling in tissue leads not only to changes in action potential morphology but can also induce spatially concordant and discordant alternans not observed in the single-cell model. In two-dimensional tissue, our results show that the model supports stable functional reentry, whose frequency is in good agreement with that observed in adult mice. Our results can be used to further constrain and validate the mathematical model of neonatal mouse cardiomyocytes with future experiments.

由单个心肌细胞（cardiomyocytes）耦合作用所催生的心肌组织时空动力学（spatio-temporal dynamics）特性，既是维持心脏正常节律的核心基础，同时也是诱发异常乃至致命性心律失常（arrhythmias）的根本原因。尽管学界已对单个心肌细胞及其跨膜电流（transmembrane currents）开展了大量研究，但由于单细胞特性与组织涌现特性之间存在非平凡的关联，系统性探究心肌组织的时空动力学仍颇具难度。数学模型已被用于填补这一研究空白，并助力学界深化对心律失常发生、发展与终止过程的认知。然而，目前尚无针对新生小鼠（neonatal mice）的心肌组织层面数学模型。本研究基于Wang与Sobie于近期提出的新生小鼠心肌细胞单细胞模型（参考文献40），对常用于评估心肌基质致心律失常性的相关特性进行预测。我们对该模型进行修改，使其可在常见实验方案下呈现明确的行为特性，并构建了空间延展版模型以探究组织涌现动力学特性。我们发现了复杂的动作电位时程（action potential duration, APD） restitution特性，其特征为对起搏频率呈现非单调依赖关系。组织中的电紧张耦合不仅会改变动作电位形态，还可诱发单细胞模型中未观察到的空间一致性与非一致性动作电位交替现象。在二维心肌组织中，我们的研究结果表明该模型可支持稳定的功能性折返（functional reentry），其折返频率与成年小鼠中观测到的结果高度吻合。本研究结果可用于未来实验，进一步约束并验证新生小鼠心肌细胞的数学模型。