Department of Mathematics and Statistics and Neuroscience Institute, Georgia State University, 30 Pryor Street, Atlanta, GA 30303, United States.
Institute for Information Technologies, Mathematics and Mechanics, Nizhni Novgorod State University, Gagarin Av. 23, 606950, Nizhni Novgorod, Russia.
Sci Rep. 2017 Jul 19;7(1):5927. doi: 10.1038/s41598-017-05198-z.
A failing heart differs from healthy hearts by an array of symptomatic characteristics, including impaired Ca transients, upregulation of Na/Ca exchanger function, reduction of Ca uptake to sarcoplasmic reticulum, reduced K currents, and increased propensity to arrhythmias. While significant efforts have been made in both experimental studies and model development to display the causes of heart failure, the full process of deterioration from a healthy to a failing heart yet remains deficiently understood. In this paper, we analyze a highly detailed mathematical model of mouse ventricular myocytes to disclose the key mechanisms underlying the continual transition towards a state of heart failure. We argue that such a transition can be described in mathematical terms as a sequence of bifurcations that the healthy cells undergo while transforming into failing cells. They include normal action potentials and [Ca] transients, action potential and [Ca] alternans, and bursting behaviors. These behaviors where supported by experimental studies of heart failure. The analysis of this model allowed us to identify that the slow component of the fast Na current is a key determining factor for the onset of bursting activity in mouse ventricular myocytes.
衰竭的心脏与健康的心脏在一系列症状特征上有所不同，包括钙瞬变受损、钠钙交换体功能上调、肌浆网钙摄取减少、钾电流减少以及心律失常倾向增加。尽管在实验研究和模型开发方面都做出了巨大努力，以展示心力衰竭的原因，但从健康心脏到衰竭心脏的恶化全过程仍然知之甚少。在本文中，我们分析了一个高度详细的小鼠心室肌细胞数学模型，以揭示导致心力衰竭的关键机制。我们认为，这种转变可以用数学术语来描述，即健康细胞在转化为衰竭细胞时所经历的一系列分岔。这些分岔包括正常的动作电位和钙瞬变、动作电位和钙交替以及爆发行为。这些行为得到了心力衰竭的实验研究的支持。对该模型的分析使我们能够确定快钠电流的慢成分是触发小鼠心室肌细胞爆发活动的关键决定因素。
