心肌细胞-成纤维细胞偶联心房组织模型的动作电位传导和阻滞。

IF 0.8 4区 数学 Q4 BIOLOGY Mathematical Medicine and Biology-A Journal of the Ima Pub Date : 2021-03-15 DOI:10.1093/imammb/dqaa014
Peter Mortensen, Hao Gao, Godfrey Smith, Radostin D Simitev
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引用次数: 3

摘要

肌细胞和成纤维细胞之间的电偶联以及成纤维细胞在心肌组织中的空间分布是诱发和维持心律失常的重要因素,但它们的作用尚不清楚。本文描述了心房组织肌细胞-成纤维细胞耦合模型的直接数值模拟和电兴奋传播和阻滞的渐近理论。特别介绍了三种理想的成纤维细胞分布:均匀分布、成纤维细胞屏障和肌细胞海峡,它们都被认为是现实成纤维细胞分布的组成块。主要动作电位生物标志物包括传导速度、峰值电位和三角测量指数在所有情况下的直接模拟估计。发现在定义每个理想成纤维细胞分布的参数的某些临界值处发生传播阻滞,并且这些临界值是准确确定的。将先前提出的渐近理论推广并应用于成纤维细胞均匀分布的情况。生物标记值是由耦合快时和慢时周期边值问题的混合解析-数值解获得的,与直接数值模拟相比效果很好。绝对耐火度的边界仅由快时间问题决定,并被发现取决于肌细胞电位的值和在传播脉冲之前钠电流的缓慢失活变量。反过来,这些量是估计从慢时间问题使用常规扰动展开,以找到耦合的肌细胞-成纤维细胞动力学的稳定状态。渐近理论给出了一个简单的解析表达式,它以惊人的准确性捕获了成纤维细胞存在时的增殖阻滞。
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Action potential propagation and block in a model of atrial tissue with myocyte-fibroblast coupling.

The electrical coupling between myocytes and fibroblasts and the spacial distribution of fibroblasts within myocardial tissues are significant factors in triggering and sustaining cardiac arrhythmias, but their roles are poorly understood. This article describes both direct numerical simulations and an asymptotic theory of propagation and block of electrical excitation in a model of atrial tissue with myocyte-fibroblast coupling. In particular, three idealized fibroblast distributions are introduced: uniform distribution, fibroblast barrier and myocyte strait-all believed to be constituent blocks of realistic fibroblast distributions. Primary action potential biomarkers including conduction velocity, peak potential and triangulation index are estimated from direct simulations in all cases. Propagation block is found to occur at certain critical values of the parameters defining each idealized fibroblast distribution, and these critical values are accurately determined. An asymptotic theory proposed earlier is extended and applied to the case of a uniform fibroblast distribution. Biomarker values are obtained from hybrid analytical-numerical solutions of coupled fast-time and slow-time periodic boundary value problems and compare well to direct numerical simulations. The boundary of absolute refractoriness is determined solely by the fast-time problem and is found to depend on the values of the myocyte potential and on the slow inactivation variable of the sodium current ahead of the propagating pulse. In turn, these quantities are estimated from the slow-time problem using a regular perturbation expansion to find the steady state of the coupled myocyte-fibroblast kinetics. The asymptotic theory gives a simple analytical expression that captures with remarkable accuracy the block of propagation in the presence of fibroblasts.

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来源期刊
CiteScore
2.20
自引率
0.00%
发文量
15
审稿时长
>12 weeks
期刊介绍: Formerly the IMA Journal of Mathematics Applied in Medicine and Biology. Mathematical Medicine and Biology publishes original articles with a significant mathematical content addressing topics in medicine and biology. Papers exploiting modern developments in applied mathematics are particularly welcome. The biomedical relevance of mathematical models should be demonstrated clearly and validation by comparison against experiment is strongly encouraged. The journal welcomes contributions relevant to any area of the life sciences including: -biomechanics- biophysics- cell biology- developmental biology- ecology and the environment- epidemiology- immunology- infectious diseases- neuroscience- pharmacology- physiology- population biology
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