title: Long-term treatment with eicosapentaenoic acid ameliorates myocardial ischemia-reperfusion injury in pigs in vivo. -Involvement of Rho-kinase pathway inhibition-.
abstract: BACKGROUND
  Eicosapentaenoic acid (EPA), the major n-3 fatty acid in fish oil, exerts cardioprotective effects against ischemic heart disease; however, the detailed mechanisms remain to be elucidated. Rho-kinase plays an important role in the pathogenesis of cardiovascular diseases including ischemia-reperfusion (I/R) injury. Thus, the hypothesis that long-term EPA treatment ameliorates myocardial I/R injury through Rho-kinase pathway inhibition in pigs in vivo was investigated.
  
  
  RESULTS
  Male pigs were treated with either a control chow or EPA (600·mg·kg⁻¹·day⁻¹) for 3 weeks (n=8 each) and were subjected to myocardial ischemia by 90-min occlusion of the left circumflex coronary artery and subsequent 60-min reperfusion. The EPA group had an increased EPA level in red blood cells (4.4 ± 0.3mol%). The EPA treatment significantly ameliorated myocardial I/R injury, including regional wall motion abnormality (EPA 5.3 ± 3.6 vs. control 35.1 ± 3.8 unit, P<0.0001), left ventricular ejection fraction (EPA 43 ± 9% vs. control 32 ± 7%, P<0.05), occurrence of ventricular arrhythmias (EPA 181 ± 73 vs. control 389 ± 51 events, P<0.0001) and histological accumulation of inflammatory cells (P<0.01). Importantly, the EPA treatment significantly inhibited myocardial Rho-kinase activity (assessed by the extent of the myosin-binding subunit phosphorylation) (EPA 0.47 ± 0.11 vs. control 0.77 ± 0.14, P<0.05) and preserved myocardial eNOS activity (EPA 0.56 ± 0.13 vs. control 0.23 ± 0.07, P<0.01) with a significant correlation noted between them.
  
  
  CONCLUSIONS
  Long-term treatment with EPA ameliorates I/R injury partly through Rho-kinase pathway inhibition in vivo.
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Japan.
authors.forename: Jun Yi
authors.initials: JY
authors.lastname: Gao
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yasuda
authors.forename: Ryuji
authors.initials: R
authors.lastname: Tsuburaya
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ito
authors.forename: Takashi
authors.initials: T
authors.lastname: Shiroto
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Hao
authors.forename: Kentaro
authors.initials: K
authors.lastname: Aizawa
authors.forename: Yoku
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Kenta
authors.initials: K
authors.lastname: Ito
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000493:pharmacokinetics / Q000494:pharmacology*; D004912:Erythrocytes / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D013318:Stroke Volume / Q000187:drug effects; D013552:Swine; D013997:Time Factors; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D015118:Eicosapentaenoic Acid; D052250:Nitric Oxide Synthase Type III; D054460:rho-Associated Kinases