Divergent antiarrhythmic effects of resveratrol and piceatannol in a whole-heart model of long QT syndrome

Background: The polyphenol resveratrol and its metabolite piceatannol have beneficial health effects including antiarrhythmic properties in ischemia/reperfusion. The objective of this study was to determine potential antiarrhythmic effects in acquired long-QT-syndrome (LQTS).

Methods and results: 26 rabbit hearts were isolated and Langendorff-perfused. The I_Kr-blocker sotalol (100μM) was infused to mimic LQTS-2. Hearts were assigned to two groups. Sotalol significantly prolonged action potential duration (APD₉₀) and QT-interval in both groups (group 1:APD₉₀: +18ms, p<0.01;QT: +59ms, p<0.01; group 2: APD₉₀: +22ms, p<0.01; QT: +30ms, p<0.01) and also significantly increased dispersion of repolarization (group 1: +21ms, p<0.01; group 2: +23ms, p<0.01). Thereafter, hearts were additionally perfused either with resveratrol (50μM, group 1, n=14) or with piceatannol (10μM, group 2, n=12). Administration of resveratrol significantly reduced APD₉₀ (-29ms, p<0.01), QT-interval(-60ms, p<0.01) and dispersion of repolarization (-26ms, p<0.01). In contrast, piceatannol did not significantly alter APD₉₀ (±0ms) but shortened QT-interval (-19ms, p<0.01) and increased dispersion of repolarization (+15ms, p<0.01). With sotalol, 7 of 14 bradycardic, AV-blocked hearts in group 1 and 8 of 12 in group 2 showed early afterdepolarizations (EAD) after lowering potassium concentration (p<0.01each). Polymorphic ventricular tachycardia (PVT) occurred in 5 of 14 (p<0.05) and 4 of 12 hearts (p=0.09) with a total number of 42 (p<0.05) and 44 episodes (p=0.07), respectively. Additional infusion of resveratrol reduced EAD (2 of 14, p=0.11) and PVT (1 of 14 hearts, p=0.16, 3 episodes, p<0.05). Piceatannol did not suppress EAD or TdP (EAD in 9 of 12 and TdP in 7 of 12 hearts,50 episodes).

Conclusion: Resveratrol showed beneficial antiarrhythmic properties in acquired LQTS. Underlying mechanism is a substantial decrease dispersion of repolarization leading to a suppression of triggered activity.