High sensitivity of the sheep pulmonary vein antrum to acetylcholine stimulation.

High sensitivity of the sheep pulmonary vein antrum to acetylcholine stimulation.
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绵羊肺静脉窦对乙酰胆碱刺激高度敏感。

DOI:
10.1152/japplphysiol.01270.2007
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发表时间:
2008-07
影响因子:
3.3
通讯作者:
--
中科院分区:
医学2区
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--
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隔离肺静脉窦可以终止心房颤动,但其基本原理尚未阐明。在本研究中,我们发现给予乙酰胆碱可不同程度地缩短绵羊心房有效不应期(ERP)。灌注15 μM乙酰胆碱后,肺静脉窦出现最短的ERP,采用标准细胞内微电极技术记录肺静脉窦、左心房后壁、房顶、游离壁及附件、右心房游离壁的ERP结果分别为52.0+/-1.6、75.1+/-2.0、77.2+/-1.7、85.6分别为 +/- 1.7、64.3 +/- 2.1 和 90.5 +/- 1.3 毫秒(P < 0.05)。免疫荧光染色显示,心房肌中毒蕈碱2型受体(M(2)R)分布也不均匀,以窦部密度最高(肺静脉窦部、左心房后壁、房顶、游离壁及心耳、右心房游离壁M(2)R相对荧光强度结果分别为62.64±2.56、53.12±2.76,分别为 51.83 +/- 2.45、47.90 +/- 2.33、55.27 +/- 2.08 和 45.53 +/- 2.02;P < 0.05),这与 ERP 分布的异质性一致。因此,肺静脉窦是一个对乙酰胆碱高度敏感的独特电生理区域,其对乙酰胆碱的强烈反应很可能与该区域密集的M(2)R分布有关。这种乙酰胆碱诱导的 ERP 异质性可能是心房颤动的底物,因此是隔离治疗的潜在电生理学基础之一。
Isolation of the pulmonary vein antrum can terminate atrial fibrillation, but the rationale has not been elucidated. In the present study, we show that sheep atrial effective refractory period (ERP) was heterogeneously shortened by acetylcholine administration. After perfusion with 15 muM acetylcholine, the shortest ERP occurred in the pulmonary vein antrum, which was recorded with the standard intracellular microelectrode technique (the ERP results in the pulmonary vein antrum, left atrial posterior wall, roof, free wall and appendage, and right atrial free wall were 52.0 +/- 1.6, 75.1 +/- 2.0, 77.2 +/- 1.7, 85.6 +/- 1.7, 64.3 +/- 2.1, and 90.5 +/- 1.3 ms, respectively; P < 0.05). Immunofluorescent staining revealed that muscarinic type 2 receptors (M(2)R) were also distributed heterogeneously in the atrial myocardium, with the highest density in the antrum (the relative fluorescent intensity results of the M(2)R in the pulmonary vein antrum, left atrial posterior wall, roof, free wall and appendage, and right atrial free wall were 62.64 +/- 2.56, 53.12 +/- 2.76, 51.83 +/- 2.45, 47.90 +/- 2.33, 55.27 +/- 2.08, and 45.53 +/- 2.02, respectively; P < 0.05), which was in accordance with the heterogeneity of ERP distribution. Thus the pulmonary vein antrum is a unique electrophysiological region with high sensitivity to acetylcholine, and its intensive response to acetylcholine is most likely associated with the dense M(2)R distribution of this region. Such an acetylcholine-induced ERP heterogeneity is possibly a substrate for atrial fibrillation and hence one of the potential electrophysiological bases for the isolation therapy.
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