title: Eicosapentaenoic acid reduces the pulmonary vein arrhythmias through nitric oxide.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Conventional microelectrodes were used to record the action potentials (APs), before and after the EPA (0.1 μM and 1.0 μM) administration with and without the presence of a nitric oxide (NO) synthase inhibitor (L-NAME, 100 μM) 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 μM, 30 min).
  
  
  RESULTS
  EPA concentration-dependently reduced the PV spontaneous beating rate (P<0.05). EPA (1.0 μM) 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 μM) 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 Ca(2+) transient and sarcoplasmic reticulum Ca(2+) content were significantly more decreased in the EPA-treated cardiomyocytes than in control PV cardiomyocytes as observed by indo-1 fluorescence.
  
  
  CONCLUSIONS
  EPA reduces PV arrhythmogenesis through the mechanoelectrical feedback generated by NO production.
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical Sciences, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Suenari
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.forename: Yu-Hsun
authors.initials: YH
authors.lastname: Kao
authors.forename: Chen-Chuan
authors.initials: CC
authors.lastname: Cheng
authors.forename: Yung-Kuo
authors.initials: YK
authors.lastname: Lin
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Kihara
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D004594:Electrophysiology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D011667:Pulmonary Veins / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D011817:Rabbits
chemical_list: D009569:Nitric Oxide; D015118:Eicosapentaenoic Acid; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester