Eicosapentaenoic acid reduces myocardial injury induced by ischemia and reperfusion in rabbit hearts.
Intake of fish oil is known to have cardioprotective effects and reduce cardiovascular mortality. However, it is not widely recognized that eicosapentaenoic acid (EPA), one of the n-3 polyunsaturated fatty acids (PUFAs), exerts beneficial effects against myocardial ischemia/reperfusion injury. The purpose of this study is to investigate whether EPA attenuates the severity of myocardial ischemia/reperfusion injury and which cellular mechanism is involved. Rabbits were treated with or without EPA (600 mg/kg/day) for 2 weeks. Infarct size was measured in open-chest rabbits after 30-minute occlusion of the left anterior descending coronary artery (LAD) and after the subsequent 3-hour reperfusion. In several groups, NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase, or charybdotoxin, a blocker of calcium-activated potassium (K(Ca)) channels, was infused intravenously beginning 20 minutes before LAD occlusion and continuing during reperfusion. Infarct size was reduced in the group treated with EPA compared with the control group (7.2 +/- 1.0% vs 24.6 +/- 2.3%; P < 0.01). The occurrence of ventricular arrhythmias in the reperfusion period tended to decrease in the EPA group. Either L-NAME or charybdotoxin partially blunted or completely abolished the infarct size-limiting effect of EPA, respectively. Eicosapentaenoic acid significantly increased the n-3:n-6 ratio of PUFA. Eicosapentaenoic acid reduces myocardial infarct size, mainly via the opening of K(Ca) channel-mediated and partially NO-mediated mechanisms in rabbit hearts.
Ogita
Hisakazu
H
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan.
Node
Koichi
K
Asanuma
Hiroshi
H
Sanada
Shoji
S
Takashima
Seiji
S
Minamino
Tetsuo
T
Soma
Masaaki
M
Kim
Jiyoong
J
Hori
Masatsugu
M
Kitakaze
Masafumi
M
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D018999:Charybdotoxin / Q000494:pharmacology; D015118:Eicosapentaenoic Acid; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000473:pathology*; D009206:Myocardium / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011817:Rabbits; D013997:Time Factors
D002316:Cardiotonic Agents; D005231:Fatty Acids, Unsaturated; D026902:Potassium Channel Blockers; D018999:Charybdotoxin; D015118:Eicosapentaenoic Acid; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester