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.