Antiarrhythmic effects of beta3-adrenergic receptor stimulation in a canine model of ventricular tachycardia

Heart Rhythm. 2008 Feb;5(2):289-97. doi: 10.1016/j.hrthm.2007.10.014. Epub 2007 Oct 9.

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.

Conclusion: Beta3-AR stimulation significantly reduces the occurrence of ventricular tachycardia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-3 Receptor Agonists*
  • Adrenergic beta-Agonists / pharmacology*
  • Animals
  • Anti-Arrhythmia Agents / pharmacology*
  • Blotting, Western
  • Death, Sudden, Cardiac / prevention & control
  • Dogs
  • Electrocardiography
  • Ethanolamines / pharmacology
  • Heart Block
  • Immunohistochemistry
  • Myocardial Contraction / drug effects*
  • Myocardial Infarction / complications
  • Potassium Channels
  • Risk Factors
  • Tachycardia, Ventricular / drug therapy*
  • Tachycardia, Ventricular / etiology
  • Tachycardia, Ventricular / physiopathology*
  • Time Factors

Substances

  • Adrenergic beta-3 Receptor Agonists
  • Adrenergic beta-Agonists
  • Anti-Arrhythmia Agents
  • Ethanolamines
  • Potassium Channels
  • BRL 37344