Piceatannol facilitates conduction block and ventricular fibrillation induction in ischemia-reperfused rabbit hearts with pacing-induced heart failure

Background: Piceatannol, a hydroxystilbene natural product, has been reported to exert antiarrhythmic action via I-Na inhibition and slow I-Na inactivation in ischemia-reperfused (IR) rat hearts. The present study aimed to clarify the proarrhythmic property of piceatannol during regional IR injury in failing rabbit hearts. Methods: Heart failure (HF) was induced by rapid right ventricular pacing for 4 weeks. The IR model was created by coronary artery ligation for 30 min, followed by reperfusion for 15 min in vivo. Simultaneous voltage and intracellular Ca2+ (Ca-i) optical mapping was then performed in isolated Langendorff-perfused hearts (n = 11 in each HF and control group). Action potential duration (APD) restitution, arrhythmogenic alternans and VF inducibility were evaluated by a dynamic pacing protocol. Conduction velocity was measured along lines across the IR and non-IR zones during pacing. Piceatannol (10 mu M) was administered after baseline studies. Results: In the HF group, piceatannol decreased conduction velocity, induced rate-dependent regional inhomogeneity of conduction delay and wavelength shortening, slowed Ca-i decay, and facilitated arrhythmogenic alternans instead of APD prolongation to increase VF inducibility. In the control group, the proarrhythmic effects of piceatannol on APD restitution, arrhythmogenic alternans and conduction delaywere offset by its antiarrhythmic effects (APD and wavelength prolongation), resulting in a neutral effect on VF inducibility. Conclusions: Piceatannol (10 mu M) is proarrhythmic in failing rabbit hearts with regional IR injury. The increased VF inducibility by piceatannol in HF suggests that its undesirable effects aremore pronounced than its benefits in failing hearts. (C) 2013 Elsevier Ireland Ltd. All rights reserved.