Resveratrol Attenuates Ventricular Arrhythmias and Improves the Long-Term Survival in Rats with Myocardial Infarction

The effects of resveratrol treatment on ventricular arrhythmia, survival, and late cardiac remodeling were evaluated in rats with myocardial infarction (MI). Three groups of rats (sham-operated, MI, and MI pre-treated with resveratrol) were treated in an in vivo MI model by ligation of left anterior descending coronary artery. The electrocardiogram signals were monitored and recorded for 24 h using an implanted telemetry transmitter. The incidence of ventricular arrhythmias during the first 24-h after MI was also evaluated. Meanwhile, invasive in vivo electrophysiology with pacing in the right ventricle was performed in each group to assess the inducibility of ventricular arrhythmias. Administration of resveratrol significantly suppressed the MI-induced ventricular tachycardia and ventricular fibrillation (0.4 +/- 0.2 in Resv group vs. 7.1 +/- 2.2 in MI group episodes per hour per rat, P < 0.01). Data also showed that the incidence of inducible ventricular tachycardia was lower in the Resv group than the MI group (46% vs. 81%, P < 0.01). The infarct size and mortality in the Resv group at 14 weeks were reduced by 20% and 33%, respectively, compared with the MI groups. Results from patch clamp recording revealed that resveratrol inhibited L-type calcium current (I (Ca-L)), and selectively enhanced ATP-sensitive K+scurrent (I (K,ATP)) in a concentration-dependent manner. These results suggested that the emerging anti-arrhythmic character induced by resveratrol treatment in rat hearts could be mainly accounted for by inhibition of I (Ca-L) and enhancement of I (K,ATP). Administration of resveratrol also improved the long-term survival by suppressing left ventricular remodeling.