Abstract 3222: Long-Term Treatment with Eicosapentaenoic Acid Suppresses Ventricular Fibrillation in a Porcine Model of Acute Myocardial Infarction: In Vivo Analysis Using Monophasic Action Potential
Background: Epidemiological and clinical studies demonstrated that eicosapentaenoic acid (EPA) reduces sudden cardiac death (SCD). Indeed, EPA is known to exert several effects in vitro (e.g. anti-thrombotic, anti-inflammatory, and endothelial effects), however, the mechanisms of the inhibitory effects of EPA on SCD in vivo remain to be fully elucidated. We thus examined whether long-term treatment with EPA exerts beneficial effects on ischemia/reperfusion (I/R) injury in vivo.
Methods: Male domestic pigs (25–30 kg) were treated with either a control chow or EPA (600 mg/kg/day, PO) for 3 weeks (n=10 each). Coronary vascular responses to serotonin (100 μg/kg, IC) and monophasic action potential (MAP) in the left ventricle (LV) were examined before and after I/R (90 min/60 min) of the left circumflex coronary artery.
Results: EPA/arachidonic acid ratio in serum was higher in the EPA than in the control group (10.3±1.7 vs. 0.2±0.1, P<0.01). The EPA treatment significantly suppressed coronary vasoconstricting responses to serotonin (−8.0±4.5 vs. −35.4±10.9%) and SCD due to ventricular fibrillation during I/R (0 vs. 60%) (both P<0.05). EPA also shortened MAP duration (measured at 90% repolarization level) both before (249±15 vs. 319±7 msec) and during I/R (−13±5 vs. −28±1% from baseline) (Figure⇓), and suppressed myocardial inflammatory cell accumulation (50±26 vs. 124±42 cells/mm2) (both P<0.05).
Conclusions: These results indicate that the long-term EPA treatment reduces I/R-induced SCD through suppression of coronary vasoconstriction and myocardial inflammation and electrical unstablization in vivo.