Effects of Acetylcholine Release Spatial Distribution on the Frequency of Atrial Reentrant Circuits: a Computational Study.

The frequency of the $ECG$ fibrillatory f-waves $(F_{\mathrm{f}})$ in atrial fibrillation $(AF)$ shows significant variations over time. Cardiorespiratory interactions through the autonomic nervous system have been suggested to play a role in such variations. Here, we tested whether the spatial distribution associated with the release of the parasympathetic neurotransmitter acetylcholine $(ACh)$ could affect the frequency of atrial reentrant circuits. Computational simulations in a human persistent-AF $3D$ atrial model were performed. We evaluated two different patterns of atrial innervation: $ACh$ release restricted to the area of the ganglionated plexi $(GP)$ and the nerves departing from them, following the so-called octopus hypothesis, and $ACh$ release distributed uniformly randomly throughout the atria. In both cases, $ACh$ release sites occupied 8% of the atria. The temporal pattern of $ACh$ release was simulated following a sinusoidal waveform of frequency 0.125 $Hz$ (respiratory frequency). Different mean levels and peak-to-peak variation ranges of $ACh$ were tested. We found that variations in the dominant frequency $F_{\mathrm{f}}$ followed the simulated temporal $ACh$ pattern in all cases, with $F_{\mathrm{f}}$ modulation being more pronounced for increasingly $larger\ ACh$ variation ranges. For the tested percentage of $ACh$ release sites (8%), the spatial distribution of $ACh$ did not have an impact on $F_{\mathrm{f}}$ modulation.