Abstract 5061: Long-Term Treatment with Eicosapentaenoic Acid Suppresses Ischemia-Induced Ventricular Fibrillation: Potential Involvement of ATP-Sensitive Potassium (KATP) Channel
Although epidemiologic studies demonstrated that eicosapentaenoic acid (EPA) reduces sudden cardiac death in patients with coronary artery disease, the mechanisms remain to be examined. It was reported that during early myocardial ischemia, activated KATP channels could cause fatal ventricular arrhythmia. We thus hypothesized that long-term treatment with EPA suppresses ischemia-induced ventricular fibrillation (VF) by inhibiting myocardial KATP channels. Male pigs were treated with either a control chow or EPA (600 mg/kg/day, PO) for 3 weeks (n=8 each). They were subjected to myocardial ischemia (90 min) by occlusion of the left circumflex coronary artery and monophasic action potential (MAP) that reflects electrical activity of the LV in vivo was measured. In the EPA group, EPA content in red blood cells was increased to 4.5±0.3 mol%, a comparable level in the clinical studies (~5.8 mol%). The EPA treatment significantly reduced the occurrence of VF and the need for DC cardioversion, with a resultant marked improvement in mortality (EPA 0% vs. control 50%, P<0.05). Furthermore, the EPA treatment significantly inhibited ischemia-induced shortening of MAP duration (measured at 90% repolarization) (EPA −19.5±3.0% vs. control −27.6±8.1%, P<0.05). Importantly, the beneficial effect of EPA on MAP was abolished by pre-treatment with diazoxide, a KATP channel opener (5 mg/kg/min for 20 min, IC) (EPA+diazoxide −27.9±6.4%, P<0.05 vs. EPA) (Figure⇓). These results indicate that long-term treatment with EPA stabilizes ventricular electrical property during myocardial ischemia partly through suppression of KATP channels in vivo.