期刊
LIFE SCIENCES
卷 89, 期 3-4, 页码 129-136出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2011.05.013
关键词
Atrial fibrillation; Electrophysiology; Fatty acids; Nitric oxide; Pulmonary vein
资金
- National Science Council of Taiwan [NSC96-2628-B-038-012-MY3, NSC97-2314-B-038-030-MY3, NSC98-2314-B-010-031-MY3]
- Wan Fang Hospital, Taipei Medical University [99wf-eva-02]
- Chi-Mei Medical Center [98CM-TMU-10]
- Taipei Veterans General Hospital [V99C1-120, V98C1-037]
Aims: Omega-3 polyunsaturated fatty acids can modulate cardiac electrophysiology and reduce the genesis of atrial fibrillation. This study investigates the potential mechanisms through which eicosapentaenoic acid (EPA) reduces pulmonary vein (PV) arrhythmogenesis. Main methods: Conventional microelectrodes were used to record the action potentials (APs), before and after the EPA (0.1 mu M and 1.0 mu M) administration with and without the presence of a nitric oxide (NO) synthase inhibitor (L-NAME, 100 mu M) in isolated rabbit PV tissue preparations. Furthermore, indo-1 fluorimetric ratio technique was used to evaluate intracellular calcium in isolated single PV cardiomyocytes with or without incubation of EPA (1.0 mu M, 30 min). Key findings: EPA concentration-dependently reduced the PV spontaneous beating rate (P<0.05). EPA (1.0 mu M) also reduced the amplitude of delayed afterdepolarizations (P<0.05). EPA hyperpolarized the maximal diastolic potential (MDP), shortened AP duration, increased AP amplitude (APA), and reduced diastolic tension and contractility. However, EPA in the presence of L-NAME or omega-9 fatty acids (oleic acid, 1.0 mu M) did not have any effect on PV spontaneous activity, AP morphology, or contractile force. A linear regression shows that the decrease in PV spontaneous beating rates induced by EPA correlated well with the changes of MDP, APA, diastolic tension, and contractile force of PVs. In addition, intracellular Ca2+ transient and sarcoplasmic reticulum Ca2+ content were significantly more decreased in the EPA-treated cardiomyocytes than in control PV cardiomyocytes as observed by indo-1 fluorescence. Significance: EPA reduces PV arrhythmogenesis through the mechanoelectrical feedback generated by NO production. (C) 2011 Elsevier Inc. All rights reserved.
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