Zhou Shengmei, Tan Alex Y, Paz Offir, Ogawa Masahiro, Chou Chung-Chuan, Hayashi Hideki, Nihei Motoki, Fishbein Michael C, Chen Lan S, Lin Shien-Fong, Chen Peng-Sheng
Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Heart Rhythm. 2008 Feb;5(2):289-97. doi: 10.1016/j.hrthm.2007.10.014. Epub 2007 Oct 9.
Beta3-adrenergic receptor (beta3-AR) stimulation inhibits cardiac contractility.
This study sought to test the hypothesis that beta3-AR stimulation is antiarrhythmic.
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.
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.
Beta3-AR stimulation significantly reduces the occurrence of ventricular tachycardia.
β3 - 肾上腺素能受体（β3 - AR）刺激可抑制心脏收缩力。
本研究旨在验证β3 - AR刺激具有抗心律失常作用这一假说。
我们为18只具有自发性室性心动过速（VT）高发病率倾向的犬植入了用于连续心电图监测的无线电发射器。18只犬中有10只接受皮下持续输注BRL37344（β3 - AR激动剂）1个月（实验组）。其余犬作为对照组。对在60天随访期内存活的所有犬的非梗死左心室游离壁取样组织进行蛋白质印迹研究。
实验组中2期VT出现的时间明显晚于对照组（P <.05）。在第一个月（0.5±0.95次/天对2.6±2.3次/天）和第二个月（0.2±0.2次/天对1.2±1.1次/天，两者P均<.05），实验组的VT发作次数均明显低于对照组。实验组的QTc比对照组短（P <.002）。实验组钠钙交换体和二氢吡啶受体的蛋白水平降低，β3 - AR表达增加，而β1 - AR、β2 - AR无变化。实验组的平均心脏重量和左心室游离壁厚度（分别为226±17 g和15.1±1.2 mm）明显低于对照组（分别为265±21 g和17.4±2.5 mm，两者P均<.05）。这两组犬的心脏性猝死发生率无差异。
β3 - AR刺激可显著减少室性心动过速的发生。
