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TITLE The effect of vagally induced dispersion of action potential duration on atrial arrhythmogenesis
AUTHORS Edward J. Vigmond, Vincent Tsoi, Samuel Kuo, Hermenegild Arevalo, James Kneller, Stanley Nattel, and Natalia Trayanova
ABSTRACT 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.
MOVIES

© CCEL 2005
Johns Hopkins University

 < < Click on the image to play the video!
Atria with 1.6 mm islands of ACh; basal ACh level = low; island ACh level = High; The model exhibits a stable figure-of-8 reentrant activity. Due to electrotonic effects, the small islands have little role in promoting APD dispersion. Hence, no break up is observed.

© CCEL 2005
Johns Hopkins University

 < < Click on the image to play the video!
Atria with 3.2 mm islands of ACh; basal ACh level = low; island ACh level = High; This model results in a quasi-stable reentrant pattern. The large island size and the high difference between the basal and island ACh level result in breakup of activity.