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The frequency of atrial fibrillatory waves is modulated by the spatiotemporal pattern of acetylcholine release : a 3D computational study

Celotto, Chiara LU ; Sánchez, Carlos ; Abdollahpur, Mostafa LU ; Sandberg, Frida LU ; Rodriguez, Jose F. ; Laguna, Pablo and Pueyo, Esther (2024) In Frontiers in Physiology 14.
Abstract

In atrial fibrillation (AF), the ECG P-wave, which represents atrial depolarization, is replaced with chaotic and irregular fibrillation waves (f waves). The f-wave frequency,
F
f, shows significant variations over time. Cardiorespiratory interactions regulated by the autonomic nervous system have been suggested to play a role in such variations. We conducted a simulation study to test whether the spatiotemporal release pattern of the parasympathetic neurotransmitter acetylcholine (ACh) modulates the frequency of atrial reentrant circuits. Understanding parasympathetic involvement in AF may guide more effective treatment approaches and could help to design autonomic markers alternative to heart rate variability (HRV), which... (More)

In atrial fibrillation (AF), the ECG P-wave, which represents atrial depolarization, is replaced with chaotic and irregular fibrillation waves (f waves). The f-wave frequency,
F
f, shows significant variations over time. Cardiorespiratory interactions regulated by the autonomic nervous system have been suggested to play a role in such variations. We conducted a simulation study to test whether the spatiotemporal release pattern of the parasympathetic neurotransmitter acetylcholine (ACh) modulates the frequency of atrial reentrant circuits. Understanding parasympathetic involvement in AF may guide more effective treatment approaches and could help to design autonomic markers alternative to heart rate variability (HRV), which is not available in AF patients. 2D tissue and 3D whole-atria models of human atrial electrophysiology in persistent AF were built. Different ACh release percentages (8% and 30%) and spatial ACh release patterns, including spatially random release and release from ganglionated plexi (GPs) and associated nerves, were considered. The temporal pattern of ACh release, ACh(
t), was simulated following a sinusoidal waveform of frequency 0.125 Hz to represent the respiratory frequency. Different mean concentrations


(



A
C
h

¯


)

and peak-to-peak ranges of ACh (ΔACh) were tested. We found that temporal variations in
F
f,
F
f(
t), followed the simulated temporal ACh(
t) pattern in all cases. The temporal mean of
F
f(
t),





F

¯



f


, depended on the fibrillatory pattern (number and location of rotors), the percentage of ACh release nodes and




A
C
h

¯


. The magnitude of
F
f(
t) modulation, Δ
F
f, depended on the percentage of ACh release nodes and ΔACh. The spatial pattern of ACh release did not have an impact on





F

¯



f


and only a mild impact on Δ
F
f. The f-wave frequency, being indicative of vagal activity, has the potential to drive autonomic-based therapeutic actions and could replace HRV markers not quantifiable from AF patients.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Frontiers in Physiology
volume
14
article number
1189464
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85182481015
  • pmid:38235381
ISSN
1664-042X
DOI
10.3389/fphys.2023.1189464
project
Diagnostic Biomarkers in Atrial Fibrillation - Autonomic Nervous System Response as a Sign of Disease Progression
language
English
LU publication?
yes
id
9b5d59c5-463f-46d2-b4df-4e61611bcf6c
date added to LUP
2024-01-19 14:02:43
date last changed
2024-04-26 06:22:16
@article{9b5d59c5-463f-46d2-b4df-4e61611bcf6c,
  abstract     = {{<p>In atrial fibrillation (AF), the ECG P-wave, which represents atrial depolarization, is replaced with chaotic and irregular fibrillation waves (f waves). The f-wave frequency, <br>
 F <br>
 f, shows significant variations over time. Cardiorespiratory interactions regulated by the autonomic nervous system have been suggested to play a role in such variations. We conducted a simulation study to test whether the spatiotemporal release pattern of the parasympathetic neurotransmitter acetylcholine (ACh) modulates the frequency of atrial reentrant circuits. Understanding parasympathetic involvement in AF may guide more effective treatment approaches and could help to design autonomic markers alternative to heart rate variability (HRV), which is not available in AF patients. 2D tissue and 3D whole-atria models of human atrial electrophysiology in persistent AF were built. Different ACh release percentages (8% and 30%) and spatial ACh release patterns, including spatially random release and release from ganglionated plexi (GPs) and associated nerves, were considered. The temporal pattern of ACh release, ACh( <br>
 t), was simulated following a sinusoidal waveform of frequency 0.125 Hz to represent the respiratory frequency. Different mean concentrations <br>
 <br>
 <br>
 (<br>
 <br>
 <br>
 <br>
 A<br>
 C<br>
 h<br>
 <br>
 ¯<br>
 <br>
 <br>
 )<br>
 <br>
 and peak-to-peak ranges of ACh (ΔACh) were tested. We found that temporal variations in<br>
 F <br>
 f, <br>
 F <br>
 f(<br>
 t), followed the simulated temporal ACh(<br>
 t) pattern in all cases. The temporal mean of <br>
 F <br>
 f(<br>
 t), <br>
 <br>
 <br>
 <br>
 <br>
 <br>
 F<br>
 <br>
 ¯<br>
 <br>
 <br>
 <br>
 f<br>
 <br>
 <br>
 , depended on the fibrillatory pattern (number and location of rotors), the percentage of ACh release nodes and <br>
 <br>
 <br>
 <br>
 <br>
 A<br>
 C<br>
 h<br>
 <br>
 ¯<br>
 <br>
 <br>
 . The magnitude of <br>
 F <br>
 f(<br>
 t) modulation, Δ <br>
 F <br>
 f, depended on the percentage of ACh release nodes and ΔACh. The spatial pattern of ACh release did not have an impact on <br>
 <br>
 <br>
 <br>
 <br>
 <br>
 F<br>
 <br>
 ¯<br>
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 <br>
 <br>
 f<br>
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 and only a mild impact on Δ <br>
 F <br>
 f. The f-wave frequency, being indicative of vagal activity, has the potential to drive autonomic-based therapeutic actions and could replace HRV markers not quantifiable from AF patients.<br>
 </p>}},
  author       = {{Celotto, Chiara and Sánchez, Carlos and Abdollahpur, Mostafa and Sandberg, Frida and Rodriguez, Jose F. and Laguna, Pablo and Pueyo, Esther}},
  issn         = {{1664-042X}},
  language     = {{eng}},
  month        = {{01}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Physiology}},
  title        = {{The frequency of atrial fibrillatory waves is modulated by the spatiotemporal pattern of acetylcholine release : a 3D computational study}},
  url          = {{http://dx.doi.org/10.3389/fphys.2023.1189464}},
  doi          = {{10.3389/fphys.2023.1189464}},
  volume       = {{14}},
  year         = {{2024}},
}