Background The pulmonary veins (PVs) have recently been shown to play a major role in the genesis of atrial fibrillation (AF). Focal “triggers” and “drivers” in the PV appear to be significantly modified or regulated by the parasympathetic nervous system. Nonetheless, the detailed autonomic profile of the PVs-especially as it compares with the posterior left atrium (PLA) and the rest of the left atrium-has not been well characterized. We hypothesized that the left atrium exhibits a heterogeneous electrophysiologic response to autonomic maneuvers, with the activation and repolarization characteristics of the PVs being different from the rest of the left atrium. Since IKAch is the ion channel that is primarily responsible for vagal effects on left atrial refractoriness, we further hypothesized that interregional variation in repolarization (in response to vagal maneuvers) is due to differences in the expression and spatial distribution of IKAch within the PVs, PLA, and left atrial appendage (LAA).
Methods In 14 dogs, high-density plaques were sutured onto the left inferior PV (8 × 5 electrodes), the PLA (7 × 3 electrodes), and LAA (7 × 3 electrodes) for bipolar electrogram recording and pacing. Epicardial mapping was performed in the PVs, PLA, and LAA under the following conditions: baseline, 20 Hz cervical vagal stimulation (VS), propranolol (P), P + VS, and P + atropine. Effective refractory periods (ERPs) were measured and conduction vectors were computed at multiple sites. Western blotting and immunostaining were performed for IKAch (Kir3.1/3.4).
Results In response to VS, there was a significant decrease in ERP (9%) in the PV compared with baseline (p = .001). In contrast, ERP changes in the PLA and LAA in response to VS were not as pronounced. In the presence of beta-blockade, vagal stimulation (P + VS) resulted in a more pronounced decrease in ERP in the PV (17.7%), PLA (19.9%), and LAA (11.6%) (P + VS vs P − PV: p < .001, PLA: p = .003, LAA: p = .036) compared with VS alone. ERP decrease in the PV and PLA was significantly greater than in the LAA (p < .05). Cumulative vagal effect (ERP difference between P + VS and P + ATR) was found to be greatest in the LAA (ERP change: LAA > PV, p = .04; LAA > PLA, p = .12). The cumulative vagal effect in the PV, PLA, and LAA corresponded to the relative expression of the IKAch subunits Kir3.1 and Kir3.4 in these regions (for both Kir3.1 and 3.4, LAA > PLA > PV). However, vagal-induced ERP shortening was significantly more heterogeneous in the PLA compared with the LAA (variance of ERP shortening: PLA > LAA, p = .04). Heterogeneity of ERP shortening corresponded to the heterogeneity of IKAch distribution in each region (variance of the number of Kir3.1-positive cells counted under six high-power (40×) fields: PV = PLA > > LAA, p < .01). With VS and/or P, there was evidence of regional conduction delay in the PVs with a significant change in activation direction. Similar activation changes were not seen in the PLA and LAA.
Conclusions The PVs and PLA demonstrate unique activation and repolarization characteristics in response to autonomic manipulation. The heterogeneity of vagal responses correlates with the pattern of IKAch distribution in the left atrium. The peculiar autonomic characteristics of the PVs and PLA may create substrate for reentry and atrial fibrillation.