Ectopic activity in the rat pulmonary vein can arise from simultaneous activation of α1- and β1-adrenoceptors
Ectopic activity in the rat pulmonary vein can arise from simultaneous activation of α1- and β1-adrenoceptors
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DOI：
10.1038/sj.bjp.0707177
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发表时间：
2007-04-01
影响因子：
7.3
通讯作者：
Findlay, I.
中科院分区：
文献类型：
--
作者：
Maupoil, V.;Bronquard, C.;Findlay, I.
背景和目的：心房颤动(房颤)是临床上最常见的电性心脏病。房颤的主要诱因是延伸到肺静脉的心肌袖中来源不明的局灶性异位活动。我们研究了去甲肾上腺素在肺静脉异位活动发生中的作用。实验方法：用等长张力仪记录雄性Wistar大鼠肺静脉条的机械活动。Krebs-Heinseleit液温36℃~37℃，充气95%O~2.5%CO2的组织浴中，电场刺激可诱发心肌细胞的抽动收缩。肺静脉异位收缩与电诱发的抽动收缩无关。去甲肾上腺素对肺静脉的作用可通过同时应用α受体激动剂苯肾上腺素和β受体激动剂异丙肾上腺素来复制，但不能单独应用。肾上腺素受体亚型的选择性激动剂和拮抗剂的使用表明，肺静脉的异位活动是由α(1)和β(1)肾上腺素受体同时刺激引起的。左心房离体条应用去甲肾上腺素并未引起异位收缩(n=10)。结论：肺静脉异位活动的起源需要同时激活a和b肾上腺素受体。这也为我们理解房颤的触发机制开辟了新的视角。
Background and purpose: Atrial fibrillation (AF) is the most common electrical cardiac disorder in clinical practice. The major trigger for AF is focal ectopic activity of unknown origin in sleeves of cardiac muscle that extend into the pulmonary veins. We examined the role of noradrenaline in the genesis of ectopic activity in the pulmonary vein.Experimental approach: Mechanical activity of strips of pulmonary vein isolated from male Wistar rats was recorded via an isometric tension meter. Twitch contractions of cardiac myocytes were evoked by electrical field stimulation in a tissue bath through which flowed Krebs-Heinseleit solution warmed to 36-37 degrees C and gassed with 95% O-2 5% CO2.Key results: The superfusion of noradrenaline induced ectopic contractions in 71 of 76 different isolated pulmonary veins. Ectopic contractions in the pulmonary vein were not associated with electrically evoked twitch contractions. The effect of noradrenaline on the pulmonary vein could be replicated by the simultaneous, but not separate, application of the alpha adrenoceptor agonist phenylephrine and the beta adrenoceptor agonist isoprenaline. The use of selective agonists and antagonists for adrenoceptor subtypes showed that ectopic activity in the pulmonary vein arose from the simultaneous stimulation of alpha(1) and beta(1) adrenoceptors. The application of noradrenaline to isolated strips of left atrium did not induce ectopic contractions (n = 10).Conclusions: These findings suggest an origin for ectopic activity in the pulmonary vein that requires activation of both a and b adrenoceptors. They also open new perspectives towards our understanding of the triggering of AF.