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 Chen, Shien-Fong Lin, Peng-Sheng Chen

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 - Feb 2008

Fingerprint

Ventricular Tachycardia
Adrenergic Receptors
Canidae
Dogs
Control Groups
Sodium-Calcium Exchanger
Calcium-Sensing Receptors
L-Type Calcium Channels
Adrenergic Agonists
Sudden Cardiac Death
Incidence
Radio
Electrocardiography
Western Blotting
Weights and Measures
Proteins

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Antiarrhythmic effects of beta3-adrenergic receptor stimulation in a canine model of ventricular tachycardia. / Zhou, Shengmei; Tan, Alex Y.; Paz, Offir; Ogawa, Masahiro; Chou, Chung Chuan; Hayashi, Hideki; Nihei, Motoki; Fishbein, Michael C.; Chen, Lan; Lin, Shien-Fong; Chen, Peng-Sheng.

In: Heart Rhythm, Vol. 5, No. 2, 02.2008, p. 289-297.

Research output: Contribution to journalArticle

Zhou, Shengmei ; Tan, Alex Y. ; Paz, Offir ; Ogawa, Masahiro ; Chou, Chung Chuan ; Hayashi, Hideki ; Nihei, Motoki ; Fishbein, Michael C. ; Chen, Lan ; Lin, Shien-Fong ; Chen, Peng-Sheng. / Antiarrhythmic effects of beta3-adrenergic receptor stimulation in a canine model of ventricular tachycardia. In: Heart Rhythm. 2008 ; Vol. 5, No. 2. pp. 289-297.
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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.",
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AU - Tan, Alex Y.

AU - Paz, Offir

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AU - Chou, Chung Chuan

AU - Hayashi, Hideki

AU - Nihei, Motoki

AU - Fishbein, Michael C.

AU - Chen, Lan

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AU - Chen, Peng-Sheng

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N2 - 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.

AB - 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.

KW - Beta3-AR agonist

KW - Sudden cardiac death

KW - Ventricular arrhythmia

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