In vitro electrophysiological mechanisms for antiarrhythmic efficacy of resveratrol, a red wine antioxidant

Resveratrol (trans-3, 4′, 5-trihydroxystilbene), a natural antioxidant derived from grapes, has beneficial effects against coronary heart disease. Its electrophysiological characteristics for antiarrhythmic efficacy are largely unknown; thus, this study aims to explore the resveratrol's antiarrhythmic effects and conduction system in isolated hearts as well as its electrophysiological effects on cardiac myocytes. In the experiment, resveratrol suppressed the ischemia/reperfusion-induced ventricular arrhythmias in Langendorff-perfused rat hearts. In the current clamp study of the experiment, resveratrol prolonged the action potential duration (APD₅₀ and APD₉₀) and suppressed the upstroke velocity of the action potential (V_max). In the voltage clamp study, resveratrol inhibited sodium inward current (I_Na) in a concentration-dependent manner and negative-shifted the voltage-dependent inactivation curve. Resveratrol also reduced the calcium inward current (I_Ca, 51.2 ± 13.3% at 100 μM). Furthermore, the transient (I_to) and sustained (I_ss) outward potassium currents were decreased 60.2 ± 5.7% and 42.3 ± 5.2% after exposure to resveratrol (100 μM), respectively. The inward rectifier potassium current (I_K1) was also reduced 24.2 ± 7.0% in the presence of resveratrol (100 μM). In the isolated heart perfusion model, resveratrol (100 μM) prolonged AV nodal refractory period, the Wenckebach cycle length and the conduction through AV node and His-Purkinje system. In conclusion, resveratrol increased the cardiac effective refractory period mainly through inhibiting the ionic channels including I_Na, I_to and I_ss which could contribute to the conversion of ischemia/reperfusion-induced lethal arrhythmias.