title: Eicosapentaenoic acid reduces ischemic ventricular fibrillation via altering monophasic action potential in pigs.
abstract: Although high intake of n-3 fatty acids is associated with reduced mortality of patients with ischemic heart disease, especially reduction in sudden cardiac death (SCD), the detailed mechanisms remain to be elucidated. Thus, the present study was designed to examine whether long-term treatment with eicosapentaenoic acid (EPA), a major component of n-3 fatty acids, reduces ischemia-induced ventricular fibrillation (VF) in pigs in vivo, and if so, what molecular mechanisms are involved. Male pigs were treated with either a control chow (control group) or a control chow plus EPA (600 mg/kg/day, PO, EPA group) for 3 weeks and were subjected to myocardial ischemia for 90 min (n=8 each) with measurement of the monophasic action potential (MAP), as a marker of ventricular electrophysiological activities. The EPA treatment significantly attenuated the occurrence of VF (control 5.1±1.7 vs. EPA 1.5±0.8 times/animal, P<0.05) and markedly reduced the mortality (control 50% vs. EPA 0%, P<0.05), with the attenuation of MAP duration shortening during ischemia (control -28.1±3.0% vs. EPA -18.2±1.4%, P<0.05). These beneficial effects of EPA were abolished by pre-treatment with cromakalim, a K(ATP) channel opener (0.3 μg/kg/min, IC). Furthermore, EPA significantly inhibited the mRNA and protein expression of Kir6.2, a major component of sarcolemmal K(ATP) channels, in both the ischemic region and non-ischemic regions. These results indicate that long-term treatment with EPA reduces ischemia-induced VF and SCD in pigs in vivo, for which attenuation of MAP duration shortening may be involved.
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Tsuburaya
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yasuda
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ito
authors.forename: Takashi
authors.initials: T
authors.lastname: Shiroto
authors.forename: Jun Yi
authors.initials: JY
authors.lastname: Gao
authors.forename: Kenta
authors.initials: K
authors.lastname: Ito
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000378:metabolism / Q000627:therapeutic use*; D019806:Cromakalim / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D015118:Eicosapentaenoic Acid / Q000378:metabolism* / Q000627:therapeutic use*; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications*; D010276:Parasympatholytics / Q000494:pharmacology / Q000627:therapeutic use; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D013552:Swine; D014693:Ventricular Fibrillation / Q000188:drug therapy*; D000099161:Kcnj11 Channel
chemical_list: D000889:Anti-Arrhythmia Agents; D019806:Cromakalim; D015118:Eicosapentaenoic Acid; D005227:Fatty Acids; D010276:Parasympatholytics; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel