Abstract 13557: Chronic Treatment with Eicosapentaenoic Acid Suppresses Ischemia-induced Ventricular Fibrillation through Inhibiting Myocardial KATP Channel in Pigs in Vivo.
Background: Although epidemiologic studies demonstrated the preventing effect of eicosapentaenoic acid (EPA) on sudden cardiac death, the mechanisms remain to be examined. Since activation of KATP channels plays a pivotal role during early myocardial ischemia, we hypothesized that chronic treatment with EPA suppresses ischemia-induced ventricular fibrillation (VF) by inhibiting myocardial KATP channels.
Methods: Male pigs were treated with either a control chow or EPA (600 mg/kg/day, PO) for 3 weeks (n=8 each) and were then subjected to myocardial ischemia (90 min) by occlusion of the left circumflex coronary artery. Monophasic action potential (MAP) duration (measured at 90% repolarization) was measured to evaluate regional electrical properties in vivo.
Results: Compared with the control group, EPA significantly attenuated the occurrence of VF (control 5.1±1.7 vs. EPA 1.5±0.8 events/animal, P<0.05) and the shortening of ischemia-induced MAP duration (control −27.6±2.9% vs. EPA −19.5±1.1%, P<0.05) (Figure). Pre-treatment with cromakalim, a KATP channel opener (0.3 mg/kg/min for 10 min IC), abolished the inhibitory effects of EPA on ischemia-induced VF (EPA+cromakalim, 6.0±1.8 events/animal, P<0.05) and MAP shortening (EPA+cromakalim, −34.9±4.7%, P<0.05). EPA also significantly inhibited the mRNA and protein expression of Kir6.2, one of the major components of KATP channels (EPA 0.51±0.08 vs. control 0.77±0.06, when standardized by GAPDH, n=8, P<0.05).
Conclusion: These results indicate that chronic treatment with EPA suppresses VF during myocardial ischemia through inhibition of myocardial KATP channels with reduced Kir6.2 expression in pigs in vivo.
- © 2010 by American Heart Association, Inc.