Chronic myocardial infarction promotes atrial action potential alternans, afterdepolarizations, and fibrillation.
Chronic myocardial infarction promotes atrial action potential alternans, afterdepolarizations, and fibrillation.
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DOI：
10.1093/cvr/cvt087
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发表时间：
2013-07-01
影响因子：
10.8
通讯作者：
Workman AJ
中科院分区：
文献类型：
--
作者：
Kettlewell S;Burton FL;Smith GL;Workman AJ
心肌梗死（MI）导致心力衰竭患者的房颤（AF）增加。我们的目的是确定慢性心室心肌梗死对家兔房颤易感性的影响，以及潜在的心房电生理和Ca 2+处理机制。在Langendorff灌注的兔心脏中，在异丙肾上腺素（ISO; 1 µM）的β-肾上腺素能刺激下，8周MI降低了AF阈值，表明AF易感性增加。这与90%复极化时心房动作电位时程（APD）-交替增加147%相关，平均APD或心房整体传导速度（CV; n = 6-13例非MI心脏，5-12例MI）无显著变化。在离体心房肌细胞中，同样在β-刺激下，MI使L-型Ca 2+电流（ICaL）密度和细胞内Ca 2+瞬时振幅分别降低35%和41%，自发去极化（SD）频率显著增加。MI增加心房肌细胞的大小和容量，并显着降低横小管密度。在用ISO灌注的非MI心脏中，ICaL阻断剂硝苯地平在浓度（0.02 µM）下导致与MI相当的ICaL降低（35%），不影响AF易感性，并降低APD。兔慢性心肌梗死重构心房结构、电生理和细胞内Ca 2+处理。在β-肾上腺素能刺激下，MI对AF的易感性增加可能是由于心房APD交替和SD的相关产生，因为稳态APD和总体CV在这些条件下未发生变化，并且可能与全细胞ICaL的相关降低无关。未来的研究可能会阐明局部传导变化以及交替的细胞和亚细胞机制对AF易感性增加的潜在贡献。
Atrial fibrillation (AF) is increased in patients with heart failure resulting from myocardial infarction (MI). We aimed to determine the effects of chronic ventricular MI in rabbits on the susceptibility to AF, and underlying atrial electrophysiological and Ca2+-handling mechanisms. In Langendorff-perfused rabbit hearts, under β-adrenergic stimulation with isoproterenol (ISO; 1 µM), 8 weeks MI decreased AF threshold, indicating increased AF susceptibility. This was associated with increased atrial action potential duration (APD)-alternans at 90% repolarization, by 147%, and no significant change in the mean APD or atrial global conduction velocity (CV; n = 6–13 non-MI hearts, 5–12 MI). In atrial isolated myocytes, also under β-stimulation, L-type Ca2+ current (ICaL) density and intracellular Ca2+-transient amplitude were decreased by MI, by 35 and 41%, respectively, and the frequency of spontaneous depolarizations (SDs) was substantially increased. MI increased atrial myocyte size and capacity, and markedly decreased transverse-tubule density. In non-MI hearts perfused with ISO, the ICaL-blocker nifedipine, at a concentration (0.02 µM) causing an equivalent ICaL reduction (35%) to that from the MI, did not affect AF susceptibility, and decreased APD. Chronic MI in rabbits remodels atrial structure, electrophysiology, and intracellular Ca2+ handling. Increased susceptibility to AF by MI, under β-adrenergic stimulation, may result from associated production of atrial APD alternans and SDs, since steady-state APD and global CV were unchanged under these conditions, and may be unrelated to the associated reduction in whole-cell ICaL. Future studies may clarify potential contributions of local conduction changes, and cellular and subcellular mechanisms of alternans, to the increased AF susceptibility.
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