title: Dynamics of atrial arrhythmias modulated by time-dependent acetylcholine concentration: a simulation study.
abstract: OBJECTIVE
  The autonomic nervous system modulates atrial activity, notably through acetylcholine (ACh) release. This time-dependent action may alter the dynamics of atrial arrhythmia. Our aim is to investigate in a computer model the changes induced by ACh release and degradation on the dynamical regime of a reentry.
  
  
  RESULTS
  A functional reentry was simulated in a 10 × 5 cm(2) two-dimensional tissue with canine atrial membrane kinetics including an ACh-dependent K(+) current. The local ACh concentration was altered over time in a circular region following a predefined spatiotemporal profile (ACh release and degradation) characterized by its maximum ACh level, time constant of release/degradation, and diameter of the region. Phase singularities were tracked to monitor the complexity of the dynamics. Four scenarios were identified: (i) the original reentry remained stable; (ii) repolarization gradients induced by ACh release caused wavebreaks, resulting in a transient complex dynamics that spontaneously converted to a single stable reentry; (iii) the reentry self-terminated through wavebreaks and wavefront interactions; (4) wavebreaks led to a complex dynamics that converted to two or three reentries that remained stable after ACh degradation. Higher ACh level, short ACh release time constant, larger heterogeneous region, and short distance between the heterogeneous region and the spiral tip were associated with higher occurrence of ACh-induced wavebreaks.
  
  
  CONCLUSIONS
  Variation of ACh concentration over time may modulate the complexity of atrial arrhythmias.
authors.affiliation: Centre de Recherche, Hôpital du Sacré-Coeur de Montréal, 5400, boul. Gouin Ouest, Montreal, QC, Canada H4J 1C5 Département de Physiologie Moléculaire et Intégrative, Institut de Génie Biomédical, Université de Montréal, Montreal, QC, Canada H3T 1J4.
authors.forename: Elhacene
authors.initials: E
authors.lastname: Matene
authors.affiliation: Centre de Recherche, Hôpital du Sacré-Coeur de Montréal, 5400, boul. Gouin Ouest, Montreal, QC, Canada H4J 1C5 Département de Physiologie Moléculaire et Intégrative, Institut de Génie Biomédical, Université de Montréal, Montreal, QC, Canada H3T 1J4.
authors.forename: Alain
authors.initials: A
authors.lastname: Vinet
authors.affiliation: Centre de Recherche, Hôpital du Sacré-Coeur de Montréal, 5400, boul. Gouin Ouest, Montreal, QC, Canada H4J 1C5 Département de Physiologie Moléculaire et Intégrative, Institut de Génie Biomédical, Université de Montréal, Montreal, QC, Canada H3T 1J4 vincent.jacquemet@umontreal.ca.
authors.forename: Vincent
authors.initials: V
authors.lastname: Jacquemet
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism* / Q000503:physiopathology; D001341:Autonomic Nervous System / Q000378:metabolism* / Q000503:physiopathology; D003198:Computer Simulation; D004285:Dogs; D006325:Heart Atria / Q000294:innervation / Q000378:metabolism* / Q000503:physiopathology; D007700:Kinetics; D008955:Models, Cardiovascular; D009716:Numerical Analysis, Computer-Assisted
chemical_list: D000109:Acetylcholine
keywords: Atrial arrhythmia; Biophysical modelling; Cholinergic action; Time-dependent parameter; Transient dynamics; Wavebreaks