In a computer model of canine atrial cells, uniform acetylcholine reduced spiral wave core meander by approximately 70% and accelerated the dominant frequency from 6.5 Hz to 17.0 Hz.
A computer model of canine atrial cells suggests that atrial fibrillation can result from relatively stable primary spiral-wave generators rather than multiple wavelets, and that vagal AF may arise from ACh-induced stabilization of these generators.
Absolute Event Rate: 17% vs 6.5%
Classical concepts of atrial fibrillation (AF) have been rooted in Moe's multiple-wavelet hypothesis and simple cellular-automaton computer model. Recent experimental work has raised questions about the multiple-wavelet mechanism, suggesting a discrete "driver region" underlying AF. We reexplored the theoretical basis for AF with a 2-dimensional computer model of a 5x10-cm sheet of atrial cells with realistic ionic and coupling properties. Vagal actions were formulated based on patch-clamp studies of acetylcholine (ACh) effects. In control, a single extrastimulus resulted in a highly meandering unstable spiral wave. Simulated electrograms showed fibrillatory activity, with a dominant frequency (DF, 6.5 Hz) that correlated with the mean rate. Uniform ACh reduced core meander of the spiral wave by approximately 70% (as measured by the standard deviation of spiral-wave tip position) and accelerated the DF to 17.0 Hz. Simulated vagally induced refractoriness heterogeneity caused wavefront breakup as accelerated reentrant activity in regions of short refractoriness impinged on regions unable to respond in a 1:1 fashion because of longer refractoriness. In 7 simulations spanning the range of conditions giving sustained AF, 5 were maintained by single dominant spiral waves. On average, 3.0+/-1.3 wavelets were present (range, 1 to 7). Most wavelets were short-lived and did not contribute to AF maintenance. In contrast to predictions of the multiple-wavelet hypothesis, but in agreement with recent experimental evidence, our model indicates that AF can result from relatively stable primary spiral-wave generators and is significantly organized. Our results suggest that vagal AF may arise from ACh-induced stabilization of the primary spiral-wave generator and disorganization of the heterogeneous tissue response. The full text of this article is available at http://www.circresaha.org.
Kneller et al. (2002) studied Atrial fibrillation. Acetylcholine (ACh) vs. Control was evaluated on Dominant frequency (DF) and core meander of the spiral wave. In a computer model of canine atrial cells, uniform acetylcholine reduced spiral wave core meander by approximately 70% and accelerated the dominant frequency from 6.5 Hz to 17.0 Hz.