Antiarrhythmic effects of beta3-adrenergic receptor stimulation in a canine model of ventricular tachycardia.
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.
Zhou
Shengmei
S
Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Tan
Alex Y
AY
Paz
Offir
O
Ogawa
Masahiro
M
Chou
Chung-Chuan
CC
Hayashi
Hideki
H
Nihei
Motoki
M
Fishbein
Michael C
MC
Chen
Lan S
LS
Lin
Shien-Fong
SF
Chen
Peng-Sheng
PS
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
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000889:Anti-Arrhythmia Agents; D004983:Ethanolamines; D015221:Potassium Channels; C057368:BRL 37344