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

Shengmei Zhou, Alex Y. Tan, Offir Paz, Masahiro Ogawa, Chung Chuan Chou, Hideki Hayashi, Motoki Nihei, Michael C. Fishbein, Lan S. Chen, Shien Fong Lin, Peng Sheng Chen

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)289-297
Number of pages9
JournalHeart Rhythm
Volume5
Issue number2
DOIs
StatePublished - Feb 2008

Keywords

  • Beta3-AR agonist
  • Sudden cardiac death
  • Ventricular arrhythmia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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