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This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 105/1/293    most recent 01270.2007v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Liang, L. Articles by Chen, Y.-H. Search for Related Content PubMed PubMed Citation Articles by Liang, L. Articles by Chen, Y.-H.

High sensitivity of the sheep pulmonary vein antrum to acetylcholine stimulation

¹Department of Cardiology, Tongji Hospital, ²Heart Rhythm Research Center, and ³Institute of Medical Genetics, Tongji University, Shanghai, China; ⁴Montreal Heart Institute, Montreal, Quebec, Canada; ⁵Heart Rhythm Management Center, Cardiovascular Center, UZ Brussel-VUB, Brussels, Belgium; ⁶Department of Cardiology, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China; and ⁷Masonic Medical Research Laboratory, Utica, New York

Submitted 4 December 2007 ; accepted in final form 23 April 2008

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 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 (M₂R) were also distributed heterogeneously in the atrial myocardium, with the highest density in the antrum (the relative fluorescent intensity results of the M₂R 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 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.

atrial fibrillation; pulmonary vein antrum; effective refractory period; muscarinic type 2 receptor