Eicosapentaenoic acid reduces ischemic ventricular fibrillation via altering monophasic action potential in pigs

Ryuji Tsuburaya, Satoshi Yasuda, Yoshitaka Ito, Takashi Shiroto, Jun Yi Gao, Kenta Ito, Hiroaki Shimokawa

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

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 (600mg/kg/day, PO, EPA group) for 3weeks and were subjected to myocardial ischemia for 90min (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 (0.3μg/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.

Original languageEnglish
Pages (from-to)329-336
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume51
Issue number3
DOIs
Publication statusPublished - 2011 Sep

Keywords

  • Fish oils
  • Ischemia
  • K channel
  • Sudden death
  • Ventricular arrhythmias

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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