title: Chronic myocardial infarction promotes atrial action potential alternans, afterdepolarizations, and fibrillation.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow G128TA, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kettlewell
authors.forename: Francis L
authors.initials: FL
authors.lastname: Burton
authors.forename: Godfrey L
authors.initials: GL
authors.lastname: Smith
authors.forename: Antony J
authors.initials: AJ
authors.lastname: Workman
mesh_terms: D000200:Action Potentials; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D006325:Heart Atria / Q000378:metabolism / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010477:Perfusion; D011817:Rabbits; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000318:Adrenergic beta-Agonists; D002121:Calcium Channel Blockers; D002118:Calcium
keywords: Action potential alternans; Afterdepolarization; Atrial fibrillation; Calcium; Myocardial infarction; T-tubule; β-Adrenergic stimulation