Submitted on December 4, 2007
Accepted on April 23, 2008
High sensitivity of the sheep pulmonary vein antrum to acetylcholine stimulation
Liang Lei1, Qin Pan2, Yi Liu2, Huaizhi Chen1, Jun Li1, Ramon Brugada3, Pedro Brugada4, Kui Hong5, Guillermo J. Perez6, Cuimei Zhao1, Jie Qi1, Yangyang Zhang1, Luying Peng2, Li Li2, and Yi-Han Chen1*
1 Department of Cardiology, Tongji Hospital, Tongji University, Shanghai, China
2 Institute of Medical Genetics, Tongji University, Shanghai, China
3 Montreal Heart Institute, Montreal, Canada
4 Department of Cardiology, Free University of Brussels, Brussel, Belgium
5 Department of Cardiology, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
6 Masonic Medical Research Laboratory, Utica, New York, United States
* To whom correspondence should be addressed. E-mail: yihanchen{at}mail.tongji.edu.cn.
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 µM acetylcholine, the shortest ERP occurred in the pulmonary vein antrum, which was recorded using the standard intracellular microelectrode technique (the ERP in the pulmonary vein antrum, left atrial posterior wall, roof, free wall and appendage, and right atrial free wall was 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 (M2R) were also distributed heterogeneously in the atrial myocardium with the highest density in the antrum (the relative fluorescent intensity of the M2R in the pulmonary vein antrum, left atrial posterior wall, roof, free wall and appendage, and right atrial free wall was 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 to be associated with the dense M2R 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.
