JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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Chronic myocardial infarction promotes atrial action potential alternans, afterdepolarizations, and fibrillation.

AIMS: 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 Ca(2+)-handling mechanisms.

METHODS AND RESULTS: 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 Ca(2+) current (I(CaL)) density and intracellular Ca(2+)-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 I(CaL)-blocker nifedipine, at a concentration (0.02 µM) causing an equivalent I(CaL) reduction (35%) to that from the MI, did not affect AF susceptibility, and decreased APD.

CONCLUSION: Chronic MI in rabbits remodels atrial structure, electrophysiology, and intracellular Ca(2+) 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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