From Millimeters to Micrometers; Re-introducing Myocytes in Models of Cardiac Electrophysiology.
From Millimeters to Micrometers; Re-introducing Myocytes in Models of Cardiac Electrophysiology.
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DOI：
10.3389/fphys.2021.763584
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发表时间：
2021
影响因子：
4
通讯作者：
Tveito A
中科院分区：
文献类型：
--
作者：
Jæger KH;Edwards AG;Giles WR;Tveito A
计算模型对心脏电生理的理解做出了重大贡献，包括心脏传导、兴奋-收缩耦合以及药物的作用和副作用。然而，心脏组织中电化学波动动力学的硅分析的准确性受到标准连续介质传导模型固有的均质化过程（空间平均）的限制。平均模型不能解析单个心肌细胞附近的复杂动力学，因为这些模型中不存在心肌细胞。在这里，我们展示了最近开发的基于表示每个心肌细胞的数学模型如何显着提高准确性，从而在耦合心肌细胞集合中建模电生理功能和功能障碍的实用性。目前心脏电生理数值模拟的金标准是基于双域模型的。在双域模型中，假设细胞外(E)空间、细胞膜(M)和细胞内(I)空间在组织中无处不在。因此，不可能研究发生在单个肌细胞附近的生物物理过程。双域模型通过平均几百个肌细胞来代表组织，这固有地限制了模型的准确性。在我们的替代方法中，E、M和I都在模型中表示，因此被称为EMI模型。EMI模型方法允许对非常接近单个肌细胞的功能重要空间中发生的生物物理过程进行详细分析，尽管代价是cpu需求显着增加。
Computational modeling has contributed significantly to present understanding of cardiac electrophysiology including cardiac conduction, excitation-contraction coupling, and the effects and side-effects of drugs. However, the accuracy of in silico analysis of electrochemical wave dynamics in cardiac tissue is limited by the homogenization procedure (spatial averaging) intrinsic to standard continuum models of conduction. Averaged models cannot resolve the intricate dynamics in the vicinity of individual cardiomyocytes simply because the myocytes are not present in these models. Here we demonstrate how recently developed mathematical models based on representing every myocyte can significantly increase the accuracy, and thus the utility of modeling electrophysiological function and dysfunction in collections of coupled cardiomyocytes. The present gold standard of numerical simulation for cardiac electrophysiology is based on the bidomain model. In the bidomain model, the extracellular (E) space, the cell membrane (M) and the intracellular (I) space are all assumed to be present everywhere in the tissue. Consequently, it is impossible to study biophysical processes taking place close to individual myocytes. The bidomain model represents the tissue by averaging over several hundred myocytes and this inherently limits the accuracy of the model. In our alternative approach both E, M, and I are represented in the model which is therefore referred to as the EMI model. The EMI model approach allows for detailed analysis of the biophysical processes going on in functionally important spaces very close to individual myocytes, although at the cost of significantly increased CPU-requirements.
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