title: Piceatannol facilitates conduction block and ventricular fibrillation induction in ischemia-reperfused rabbit hearts with pacing-induced heart failure.
abstract: BACKGROUND
  Piceatannol, a hydroxystilbene natural product, has been reported to exert antiarrhythmic action via INa inhibition and slow INa 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 Ca(2+) (Cai) 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 μM) 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 Cai 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 delay were offset by its antiarrhythmic effects (APD and wavelength prolongation), resulting in a neutral effect on VF inducibility.
  
  
  CONCLUSIONS
  Piceatannol (10 μM) is proarrhythmic in failing rabbit hearts with regional IR injury. The increased VF inducibility by piceatannol in HF suggests that its undesirable effects are more pronounced than its benefits in failing hearts.
authors.affiliation: Division of Cardiology, Department of Medicine, Chang Gung Memorial Hospital, Linko, Taiwan; Chang Gung University College of Medicine, Taoyuan, Taiwan. Electronic address: 2867@adm.cgmh.org.tw.
authors.forename: Chung-Chuan
authors.initials: CC
authors.lastname: Chou
authors.affiliation: Division of Cardiology, Department of Medicine, Chang Gung Memorial Hospital, Linko, Taiwan.
authors.forename: Po-Cheng
authors.initials: PC
authors.lastname: Chang
authors.affiliation: Division of Cardiology, Department of Medicine, Chang Gung Memorial Hospital, Linko, Taiwan; Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Ming-Shien
authors.initials: MS
authors.lastname: Wen
authors.affiliation: Department of Anesthesia, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Lee
authors.affiliation: Division of Cardiology, Department of Medicine, Chang Gung Memorial Hospital, Linko, Taiwan.
authors.forename: Hung-Ta
authors.initials: HT
authors.lastname: Wo
authors.affiliation: Division of Cardiology, Department of Medicine, Chang Gung Memorial Hospital, Linko, Taiwan; Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: San-Jou
authors.initials: SJ
authors.lastname: Yeh
authors.affiliation: Division of Cardiology, Department of Medicine, Chang Gung Memorial Hospital, Linko, Taiwan.
authors.forename: Delon
authors.initials: D
authors.lastname: Wu
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac; D006327:Heart Block / Q000139:chemically induced*; D006329:Heart Conduction System / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D010477:Perfusion; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011817:Rabbits; D013267:Stilbenes / Q000494:pharmacology*; D014693:Ventricular Fibrillation / Q000139:chemically induced*
chemical_list: D013267:Stilbenes; C041525:3,3',4,5'-tetrahydroxystilbene; D011505:Protein-Tyrosine Kinases; D002118:Calcium
keywords: Animal studies; Electrophysiology; Heart failure; Ischemia–reperfusion; Mapping; Piceatannol