High sensitivity of the sheep pulmonary vein antrum to acetylcholine stimulation

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.