The effect of vagally induced dispersion of action potential duration on atrial arrhythmogenesis.
OBJECTIVE
The purpose of this study is to ascertain the effects of spatially variable ACh distributions on arrhythmogenesis in a morphologically realistic computer model of canine atria.


BACKGROUND
Vagal stimulation releases acetylcholine (ACh), which causes a dose-dependent reduction in action potential duration (APD) in the atria. Due to the nonuniform distribution of nerve endings, APD dispersion may result, which has been shown to play a role in the breakup of activity.


METHODS
Reentry was initiated in a computationally efficient, morphologically realistic computer model of the atria. Discrete regions corresponding to ACh release sites, referred to as islands, were assigned shortened APDs in an ACh-dependent fashion. Island APD was varied as well as the basal APD. The window of vulnerability for ectopic beat-induction of sustained reentry was determined for both left atrial(LA) and right atrial (RA) stimulation. The resulting reentries were categorized based on type and location.


RESULTS
1) Atrial geometry severely restricts the formation of reentrant circuits. 2) Wave fractionation only occurred for large differences between island and basal APD. 3) Small ACh concentration differences produced stable figure-of-8 reentrant patterns. 4) Large islands displayed more wave breakup but could sometimes anchor reentries.


CONCLUSIONS
Large APD gradients produced by ACh heterogeneity can lead to a breakdown of organized activity.
Vigmond
Edward J
EJ
Department of Electrical and Computer Engineering, University of Calgary, Calgary, Alberta, Canada.
Tsoi
Vincent
V
Kuo
Samuel
S
Arevalo
Hermenigeld
H
Kneller
James
J
Nattel
Stanley
S
Trayanova
Natalia
N
D000109:Acetylcholine / Q000502:physiology*; D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001016:Aortic Bodies / Q000503:physiopathology; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000503:physiopathology; D003198:Computer Simulation; D004285:Dogs; D004558:Electric Stimulation; D006325:Heart Atria / Q000503:physiopathology*; D008955:Models, Cardiovascular; D013997:Time Factors
D000109:Acetylcholine