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.
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.
Authors: J M Cao; M C Fishbein; J B Han; W W Lai; A C Lai; T J Wu; L Czer; P L Wolf; T A Denton; I P Shintaku; P S Chen; L S Chen Journal: Circulation Date: 2000-04-25 Impact factor: 29.690
Authors: S Zhou; J M Cao; Z D Tebb; T Ohara; H L Huang; C Omichi; M H Lee; B H Kenknight; L S Chen; M C Fishbein; H S Karagueuzian; P S Chen Journal: J Cardiovasc Electrophysiol Date: 2001-09
Authors: J M Cao; L S Chen; B H KenKnight; T Ohara; M H Lee; J Tsai; W W Lai; H S Karagueuzian; P L Wolf; M C Fishbein; P S Chen Journal: Circ Res Date: 2000-04-14 Impact factor: 17.367
Authors: Moshe Swissa; Shengmei Zhou; Ignacio Gonzalez-Gomez; Che-Ming Chang; Angela C Lai; Adam W Cates; Michael C Fishbein; Hrayr S Karagueuzian; Peng-Sheng Chen; Lan S Chen Journal: J Am Coll Cardiol Date: 2004-03-03 Impact factor: 24.094