Remodelling of action potential and intracellular calcium cycling dynamics during subacute myocardial infarction promotes ventricular arrhythmias in Langendorff-perfused rabbit hearts
Remodelling of action potential and intracellular calcium cycling dynamics during subacute myocardial infarction promotes ventricular arrhythmias in Langendorff-perfused rabbit hearts
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DOI：
10.1113/jphysiol.2006.120659
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发表时间：
2007-05-01
影响因子：
5.5
通讯作者：
Chen, Peng-Sheng
中科院分区：
文献类型：
--
作者：
Chou, Chung-Chuan;Zhou, Shengmei;Chen, Peng-Sheng
我们假设，在心肌梗死后，心肌梗死周围区域动作电位重构和细胞内钙(CaI)动力学改变有助于室性心律失常的发生。为了验证这一假说，我们对15只心肌梗死兔进行了一周的左心室CAI和膜电位(V-m)的同步光学标测。室性早搏多起源于梗死区，37%的室性早搏在Vm除极前出现CaI升高，提示其病因为反向兴奋-收缩偶联。在电诱发的室颤中，最高主频出现在梗死区的有61例。主频最高的部位动作电位时程恢复更陡峭，对起搏诱发的CAI交替的敏感性高于远离梗塞的部位。室颤时的波破裂往往发生在持续升高的CAI部位。心得安可使动作电位时程恢复平坦，波间歇减少，室颤转为室性心动过速。结论：心肌梗死亚急性期，梗死区表现为动作电位时程恢复斜率陡峭、CAI动态不稳定的区域。这些变化可能会促进室性早搏，并增加室颤期间波的发生率。尽管亚急性心肌梗死后组织异质性增加创造了高度致心律失常的底物，但动态动作电位和CaI循环重构也有助于这种情况下室颤的启动和维持。
We hypothesize that remodelling of action potential and intracellular calcium (Cai) dynamics in the peri-infarct zone contributes to ventricular arrhythmogenesis in the postmyocardial infarction setting. To test this hypothesis, we performed simultaneous optical mapping of Cai and membrane potential (V-m) in the left ventricle in 15 rabbit hearts with myocardial infarction for 1 week. Ventricular premature beats frequently originated from the peri-infarct zone, and 37% showed elevation of Cai prior to Vm depolarization, suggesting reverse excitation-contraction coupling as their aetiology. During electrically induced ventricular fibrillation, the highest dominant frequency was in the peri-infarct zone in 61 of 70 episodes. The site of highest dominant frequency had steeper action potential duration restitution and was more susceptible to pacing-induced Cai alternans than sites remote from infarct. Wavebreaks during ventricular fibrillation tended to occur at sites of persistently elevated Cai. Infusion of propranolol flattened action potential duration restitution, reduced wavebreaks and converted ventricular fibrillation to ventricular tachycardia. We conclude that in the subacute phase of myocardial infarction, the peri-infarct zone exhibits regions with steep action potential duration restitution slope and unstable Cai dynamics. These changes may promote ventricular extrasystoles and increase the incidence of wavebreaks during ventricular fibrillation. Whereas increased tissue heterogeneity after subacute myocardial infarction creates a highly arrhythmogenic substrate, dynamic action potential and Cai cycling remodelling also contribute to the initiation and maintenance of ventricular fibrillation in this setting.