title: Antiarrhythmic effects of beta3-adrenergic receptor stimulation in a canine model of ventricular tachycardia.
abstract: BACKGROUND
  Beta3-adrenergic receptor (beta3-AR) stimulation inhibits cardiac contractility.
  
  
  OBJECTIVE
  This study sought to test the hypothesis that beta3-AR stimulation is antiarrhythmic.
  
  
  METHODS
  We implanted a radio transmitter for continuous electrocardiogram monitoring in 18 dogs with a tendency for high incidence of spontaneous ventricular tachycardia (VT). Ten of 18 had subcutaneous continuous BRL37344 (beta3-AR agonist) infusion (experimental group) for 1 month. The other dogs were controls. Western blotting studies were performed on tissues sampled from the noninfarcted left ventricular free wall of all dogs that survived the 60-day follow-up period.
  
  
  RESULTS
  Phase 2 VT appeared significantly later in the experimental group than in the control group (P <.05). The number of VT episodes in the experimental group was significantly lower than in the control group during both the first month (0.5 +/- 0.95 episodes/day vs. 2.6 +/- 2.3 episodes/day) and the second month (0.2 +/- 0.2 episode/day vs. 1.2 +/- 1.1 episodes/day, P <.05 for both). The experimental group had shorter QTc than control (P <.002). The experimental group had decreased protein levels for sodium calcium exchanger and dihydropyridine receptor, increased beta3-AR expression, without changes in beta1-AR, beta2-AR. The average heart weight and the left ventricular free wall thickness in the experimental group (226 +/- 17 g and 15.1 +/- 1.2 mm, respectively) was significantly lower than in the control group (265 +/- 21 g and 17.4 +/- 2.5 mm, respectively, P <.05 for both). There was no difference in the incidences of sudden cardiac death in these 2 groups of dogs.
  
  
  CONCLUSIONS
  Beta3-AR stimulation significantly reduces the occurrence of ventricular tachycardia.
authors.affiliation: Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Shengmei
authors.initials: S
authors.lastname: Zhou
authors.forename: Alex Y
authors.initials: AY
authors.lastname: Tan
authors.forename: Offir
authors.initials: O
authors.lastname: Paz
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ogawa
authors.forename: Chung-Chuan
authors.initials: CC
authors.lastname: Chou
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Motoki
authors.initials: M
authors.lastname: Nihei
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fishbein
authors.forename: Lan S
authors.initials: LS
authors.lastname: Chen
authors.forename: Shien-Fong
authors.initials: SF
authors.lastname: Lin
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Chen
mesh_terms: D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D015153:Blotting, Western; D016757:Death, Sudden, Cardiac / Q000517:prevention & control; D004285:Dogs; D004562:Electrocardiography; D004983:Ethanolamines / Q000494:pharmacology; D006327:Heart Block; D007150:Immunohistochemistry; D009200:Myocardial Contraction / Q000187:drug effects*; D009203:Myocardial Infarction / Q000150:complications; D015221:Potassium Channels; D012307:Risk Factors; D017180:Tachycardia, Ventricular / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000889:Anti-Arrhythmia Agents; D004983:Ethanolamines; D015221:Potassium Channels; C057368:BRL 37344