Towards an integrated understanding of cardiac arrhythmogenesis − Growing roles of experimental pathology
Towards an integrated understanding of cardiac arrhythmogenesis − Growing roles of experimental pathology
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DOI：
10.1111/pin.12487
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发表时间：
2017-01
影响因子：
2.2
通讯作者：
Hideo Tanaka;T. Matsuyama;T. Takamatsu
中科院分区：
文献类型：
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作者：
Hideo Tanaka;T. Matsuyama;T. Takamatsu
心律失常长期以来被认为是心脏内电脉冲启动和传导的紊乱。然而，仅从电生理学的角度，还不能完全理解神经元生成的潜在机制。这篇综述文章从非电方面讨论了心律失常的发病机制，通过功能分子的时空成像结合活心脏组织的形态学分析阐明了这一点。由心肌损伤引起的细胞内Ca2+（[Ca2+]i）过载引起可导致异常兴奋的Ca2+波，即，引发了心律失常由缺血、心力衰竭或T管重塑引起的肌浆网Ca2+释放抑制导致时空不均匀的[Ca2+]i动力学，可能干扰冲动传导，导致折返性快速性心律失常。差距连接介导的细胞间通讯受损，引起心肌脉冲传播紊乱，也导致折返性心律失常。心肌中的非心肌细胞（尤其是成纤维细胞）的介入也可能通过与心肌细胞的异细胞间隙连接偶联促进心肌细胞生成。此外，心肌组织学的改变，例如，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。这些分子，功能和心肌的形态学特征的整合，揭示了实验病理学方法，将为理解心律失常的发病机制铺平了新的道路。
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 Ca2+ ([Ca2+]i) overload, caused by myocardial injury, provokes Ca2+ waves that could lead to abnormal excitations, i.e., triggered arrhythmias. Depressed Ca2+ release from the sarcoplasmic reticulum, caused by ischemia, heart failure, or T‐tubular remodeling, results in spatiotemporally inhomogeneous [Ca2+]i 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.