Abstract 1361: Heterogeneous Distribution Of Muscarinic Receptors Contributes To The Substrate For Vagal Atrial Fibrillation
Introduction: Parasympathetic influences are thought to play an important role in the genesis of focal atrial fibrillation (AF). Since heterogeneity of repolarization contributes to AF, we hypothesized that muscarinic (M2) receptors are unevenly distributed in the PVs and left atrium and that this creates heterogeneity of repolarization in response to vagal stimulation (VS).
Methods: Pulmonary veins (PV), posterior left atrium (PLA) and left atrial appendage (LAA) were harvested from 5 normal dogs. Sections of tissue were immunostained for M2 receptors and their distribution was quantified by counting the number of stained tissue elements. In 8 normal dogs median thoracotomy was performed for epicardial bipolar mapping in the PVs (2×2 electrodes), PLA (7×3 electrodes) and LAA (7×3 electrodes). Effective refractory periods (ERP) were measured at baseline and after left cervical VS at 20Hz.
Results: M2 receptors were localized in and around nerve bundles and fibers, perivascularly and in individual cardiomyocytes (fig A⇓). M2 distribution was more pronounced in the PLA than the other two regions (M2 stained cells/cm2: PLA=17.8±8.3, PV=14.3±7.3, LAA=14.5±8, p=0.012; fig B⇓). VS led to ERP shortening in PV, PLA and LAA, with ERP shortening being most pronounced in the PLA (ΔERP PLA=−25.6, PV=−20, LAA=−20.5 msec, p<0.05; fig C⇓). The M2 distribution patterns correlated significantly with regional ERP shortening (correl: −0.9, p=0.02).
Conclusions: The distribution of M2 receptors correlates with the heterogeneity of vagal responses in the left atrium. The M2 receptors preferentially located in the PLA, suggesting an important role for this region in creation of vagal AF.