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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 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
Pages (from-to)289-297
Number of pages9
JournalHeart Rhythm
Volume5
Issue number2
DOIs
StatePublished - 1 Feb 2008

Keywords

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

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