Tanaka Hideo, Matsuyama Taka-Aki, Takamatsu Tetsuro
Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Medical Photonics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Pathol Int. 2017 Jan;67(1):8-16. doi: 10.1111/pin.12487. Epub 2016 Dec 20.
Cardiac arrhythmias have long been regarded as derangement of electrical impulse initiation and conduction within the heart. However, underlying mechanisms for arrhythmogenesis are not fully understood solely from the electrophysiological viewpoint. This review article discusses pathogenesis of arrhythmias from non-electrical aspects, which were elucidated by spatiotemporal imaging of functional molecules in combination with morphological analysis of living heart tissues. Intracellular Ca ([Ca ] ) overload, caused by myocardial injury, provokes Ca waves that could lead to abnormal excitations, i.e., triggered arrhythmias. Depressed Ca release from the sarcoplasmic reticulum, caused by ischemia, heart failure, or T-tubular remodeling, results in spatiotemporally inhomogeneous [Ca ] dynamics that could disturb impulse conduction, leading to reentrant tachyarrhythmias. Impairment of the gap junction-mediated intercellular communications, which provokes derangement of impulse propagation of the myocardium, also leads to reentrant arrhythmias. Interpositions of non-cardiomyocytes, especially fibroblasts, in the myocardium could also contribute to arrhythmogenesis via heterocellular gap-junctional coupling with cardiomyocytes. Furthermore, alterations in myocardial histology, e.g., density and arrangements of myocytes in association with gap-junctional distributions, could constitute important pathologic bases of atrial fibrillation. Integration of these molecular, functional, and morphological features of the myocardium, unveiled by experimental pathological approaches, would pave a new way for understanding pathogenesis of cardiac arrhythmias.
长期以来，心律失常一直被视为心脏内电冲动起始和传导的紊乱。然而，仅从电生理学角度，心律失常发生的潜在机制尚未完全明了。这篇综述文章从非电方面探讨了心律失常的发病机制，这些机制是通过功能分子的时空成像与活体心脏组织的形态学分析相结合而阐明的。心肌损伤引起的细胞内钙（[Ca]）超载会引发钙波，进而导致异常兴奋，即触发心律失常。缺血、心力衰竭或T管重塑引起的肌浆网钙释放减少，会导致[Ca]动力学在时空上不均匀，从而干扰冲动传导，引发折返性快速心律失常。缝隙连接介导的细胞间通讯受损会引发心肌冲动传播紊乱，也会导致折返性心律失常。心肌中非心肌细胞（尤其是成纤维细胞）的插入也可能通过与心肌细胞的异细胞缝隙连接耦合而导致心律失常。此外，心肌组织学改变，如与缝隙连接分布相关的心肌细胞密度和排列，可能构成心房颤动的重要病理基础。通过实验病理学方法揭示的心肌这些分子、功能和形态特征的整合，将为理解心律失常的发病机制开辟一条新途径。
