Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Medicine, F. Edward Hébert School of Medicine, Bethesda, MD, USA.
Methods Mol Biol. 2022;2399:247-259. doi: 10.1007/978-1-0716-1831-8_11.
While mitochondrial dysfunction has been implicated in the pathogenesis of cardiac arrhythmias, how the abnormality occurring at the organelle level escalates to influence the rhythm of the heart remains incompletely understood. This is due, in part, to the complexity of the interactions formed by cardiac electrical, mechanical, and metabolic subsystems at various spatiotemporal scales that is difficult to fully comprehend solely with experiments. Computational models have emerged as a powerful tool to explore complicated and highly dynamic biological systems such as the heart, alone or in combination with experimental measurements. Here, we describe a strategy of integrating computer simulations with optical mapping of cardiomyocyte monolayers to examine how regional mitochondrial dysfunction elicits abnormal electrical activity, such as rebound and spiral waves, leading to reentry and fibrillation in cardiac tissue. We anticipate that this advanced modeling technology will enable new insights into the mechanisms by which changes in subcellular organelles can impact organ function.
虽然线粒体功能障碍与心律失常的发病机制有关，但细胞器水平的异常如何逐渐影响心脏节律仍不完全清楚。部分原因在于，心脏电、机械和代谢子系统在不同时空尺度上形成的相互作用非常复杂，仅通过实验很难完全理解。计算模型已成为探索复杂且高度动态的生物系统（如心脏）的有力工具，可单独使用或与实验测量相结合。在这里，我们描述了一种将计算机模拟与心肌细胞单层的光学标测相结合的策略，以研究局部线粒体功能障碍如何引发异常电活动，如折返和螺旋波，从而导致心脏组织中的折返和纤颤。我们预计，这项先进的建模技术将使我们能够深入了解亚细胞细胞器的变化如何影响器官功能的机制。
