title: Testosterone replacement increases aged pulmonary vein and left atrium arrhythmogenesis with enhanced adrenergic activity.
abstract: BACKGROUND
  Aging and testosterone deficiency contribute to the pathogenesis of atrial fibrillation (AF). We determine the effects of testosterone replacement on the electrophysiology and arrhythmogenesis of pulmonary vein (PV) and left atrium (LA) in aged rabbits.
  
  
  METHODS
  Electrocardiography, heart rate variability, echocardiography, Western blot and conventional microelectrodes were used in aged rabbits (age, >2 years) with and without (control) testosterone treatment (10mg/kg, 12 weeks).
  
  
  RESULTS
  Testosterone-treated aged rabbits had longer corrected QT interval, higher low frequency/high frequency, greater left ventricle (LV) mass but lower LA total emptying fraction and LV ejection fraction than control rabbits. In tissue preparations, the spontaneous rate was faster for testosterone-treated PVs than for control PVs. Angiotensin II concentration-dependently increased the amplitude of delayed afterdepolarizations (DADs) in testosterone-treated PVs but only did so at the highest angiotensin II concentration (100 nM) in control PVs. Isoproterenol increased the incidence of early afterdepolarizations (EADs) and DADs in testosterone-treated PVs but not in control PVs. Testosterone-treated PVs had more H2O2-induced burst firing and EADs than control PVs. Testosterone-treated LAs had more isoproterenol-induced DADs and spontaneous activity than did control LAs. However, acetylcholine infusion and rapid atrial pacing (10-20 Hz) induced AF in control LAs but not in testosterone-treated LAs. In addition, as compared with control LAs, testosterone-treated LAs expressed more androgen receptor, β1-adrenergic receptor, and Cav 1.2 and less G protein-coupled receptor kinase-2 and Kv 4.2.
  
  
  CONCLUSIONS
  Testosterone replacement increased arrhythmogenesis in PV and LA by enhancing adrenergic activity in aged rabbits.
authors.affiliation: Division of Cardiology, Tzu-Chi General Hospital, Hualien, Taiwan.
authors.forename: Wen-Chin
authors.initials: WC
authors.lastname: Tsai
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of General Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ting-I
authors.initials: TI
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Hsun
authors.initials: YH
authors.lastname: Kao
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Cardiology, Sijhih Cathay General Hospital, New Taipei City, Taiwan.
authors.forename: Yen-Yu
authors.initials: YY
authors.lastname: Lu
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yung-Kuo
authors.initials: YK
authors.lastname: Lin
authors.affiliation: School of medicine, National Yang-Ming University, Taipei, Taiwan; Division of Cardiology, Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address: a9900112@ms15.hinet.net.
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000375:Aging / Q000187:drug effects*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D016279:Atrial Function, Left / Q000187:drug effects*; D008297:Male; D009924:Organ Culture Techniques; D011667:Pulmonary Veins / Q000187:drug effects* / Q000503:physiopathology; D011817:Rabbits; D013739:Testosterone / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D000318:Adrenergic beta-Agonists; D013739:Testosterone
keywords: Adrenergic activity; Atrial fibrillation; Pulmonary vein; Testosterone