Kügler Philipp
Institute of Applied Mathematics and Statistics, University of Hohenheim, Schloss 1, 70599 Stuttgart, Germany.
Research Group Mathematical Methods in Molecular and Systems Biology, Radon Institute for Computational and Applied Mathematics, Altenbergerstrasse 69, 4040 Linz, Austria.
PLoS One. 2016 Mar 15;11(3):e0151178. doi: 10.1371/journal.pone.0151178. eCollection 2016.
Early afterdepolarizations (EADs) are pathological oscillations in cardiac action potentials during the repolarization phase and may be caused by drug side effects, ion channel disease or oxidative stress. The most widely observed EAD pattern is characterized by oscillations with growing amplitudes. So far, its occurence has been explained in terms of a supercritical Hopf bifurcation in the fast subsystem of the action potential dynamics from which stable limit cycles with growing amplitudes emerge. The novel contribution of this article is the introduction of two alternative explanations of EAD genesis with growing amplitudes that do not involve stable limit cycles in fast subsystems. In particular, we demonstrate that EAD patterns with growing amplitudes may alternatively arise due to a delayed subcritical Hopf bifurcation or an unstable manifold of a saddle focus fixed point in the full fast-slow system modelling the action potential. Our work extends the list of possible dynamical EAD mechanisms and may contribute to a classification of drug effects in preclinical cardiotoxicity testing.
早期后去极化（EADs）是复极化阶段心脏动作电位中的病理性振荡，可能由药物副作用、离子通道疾病或氧化应激引起。最常观察到的EAD模式的特征是振幅不断增大的振荡。到目前为止，其发生已根据动作电位动力学快速子系统中的超临界霍普夫分岔来解释，由此出现振幅不断增大的稳定极限环。本文的新贡献是引入了两种关于振幅不断增大的EAD发生的替代解释，这些解释不涉及快速子系统中的稳定极限环。特别是，我们证明，振幅不断增大的EAD模式可能 alternatively 由于延迟亚临界霍普夫分岔或模拟动作电位的完整快慢系统中鞍点焦点不动点的不稳定流形而出现。我们这项工作扩展了可能的动态EAD机制列表，并可能有助于在临床前心脏毒性测试中对药物效应进行分类。 （注：原文中“alternatively”翻译为“或者”，但放在句中语义不太通顺，这里根据语境意译为“另一种方式”更合适，不过要求不能添加其他解释说明，所以保留原文形式放在此处。）
