Ganglionated plexi stimulation induces pulmonary vein triggers and promotes atrial arrhythmogenecity: In silico modeling study

Fig 1. Model of GP and nerves based on the “octopus hypothesis” [6]. The PVs and LA area are indicated in yellow and blue, respectively. The GP and nerves are indicated in green.

Fig 2. Late phase 3 early afterdepolarization (EAD)-like depolarization. Action potentials (APs), intracellular calcium concentration, sodium-calcium exchanger (NCX) current, and Na+ current before and after the pacing cycle length (PCL) change from 100 to 1000 ms are shown. A late phase 3 EAD-like depolarization is observed at the first beat after the PCL change. Increases in the intracellular calcium, NCX current, and Na+ current accompanied the late phase 3 EAD-like depolarization. The red dots represent the pacing time points.

Fig 3. Spontaneous action potential in the pulmonary vein (PV). (A) Ganglionated plexus (GP) and nerve model based on the octopus hypothesis.[6] (B) Action potentials (APs) at 5 points on the PV and left atrium (LA) are shown after rapid pacing in the left superior PV (location 2). Sequential wave propagation from point 1 to 5 is observed. Red dots represent the pacing time points. (C) Three-dimensional AP maps showing wave propagation. (D) Approximately 7 s after rapid pacing, the wave propagation becomes irregular and degenerates to atrial fibrillation (AF).

Fig 4. A local reentry in the maintenance of atrial fibrillation. (A) The location of reentry. The numbers indicate the locations of the action potentials (APs) shown in (H). (B) Phase singularity (PS) map showing the trajectory of the center of the reentry near the PV-LA junction. (C) Isochronal map showing the reentry near the PV-LA junction. (D) AP at a location (1 in (A)) in the reentry. (E) [Ca2+]i at the location (1 in (A)) where AP in (D) was recorded. (F) Magnification of the box (marked *) in (D). (G) Magnification of the box (marked **) in (E). [Ca2+]i did not always increase at each depolarization in (F). (H) APs at 5 locations (marked in (A)) around the reentry. APs exhibit the rotational propagation near the PV-LA junction.

Fig 5. Wave-dynamics parameters following parasympathetic stimulation. Complex fractionated atrial electrogram (CFAE) and phase singularity (PS) maps for ACh concentrations of 0 and 0.03 μM are shown. The CFAE cycle length (CFAE-CL) is shorter overall, and more PSs are observed for an ACh concentration of 0.03 μM than 0 μM. The action potential (AP) at a point in the right anterior ganglionated plexus is shown for both ACh concentrations. The APD is shorter for ACh concentrations of 0.03 than 0 μM.

Fig 6. Two patterns of virtual ablations. Ganglionated plexus (GP)-only ablation did not terminate atrial fibrillation (AF), whereas circumferential pulmonary vein isolation (CPVI) including the GP areas terminated AF at approximately 9 s after the virtual ablation was performed. In the case of CPVI including the GP areas, activity was still observed within the ablation line around the right inferior pulmonary vein (PV). Action potentials (APs) in the left atrium (LA) and PV are shown for both patterns of virtual ablations.