Exendin-4 attenuates ischemia-induced ventricular arrhythmias in rats

BACKGROUND: Glucagon-like peptide-1 and its receptor agonist-exendin-4 (Ex-4) have been shown to provide beneficial effects for cardiovascular diseases. This study investigated the effects of Ex-4 on ischemia-induced ventricular arrhythmias in rats. METHODS: Anesthetized male rats were once treated with Ex-4 (5 μg/kg, i.v.) 1 h before ischemia in the absence and/or presence of 5-hydroxydecanoic acid (5-HD, 10 mg/kg, i.v., a specific inhibitor of mitochondrial ATP-sensitive potassium [KATP] channels) which were once injected 10 min before ischemia. And then subjected to ischemia for 30 min. Ventricular arrhythmias were assessed. RESULTS: During the 30-min ischemia, Ex-4 significantly reduced the incidence of ventricular fibrillation (VF) (p < 0.05). The duration of ventricular tachycardia (VT) + VF, the number of VT + VF episodes and the severity of arrhythmias were all significantly reduced by Ex-4 compared to those in myocardial ischemia group (p < 0.05 for all). Administration of 5-HD abolished the protective effects of Ex-4 on VF incidence, the duration of VT + VF, the number of VT + VF episodes and the severity of arrhythmias (p < 0.05 for all). CONCLUSIONS: This study suggested that Ex-4 could attenuate ischemia-induced ventricular arrhythmias in rats in which mitochondrial KATP channels may be involved.