Heterogeneous Atrial Denervation Creates Substrate for Sustained Atrial Fibrillation

Abstract

Background-Heterogeneous electrophysiological properties, which may be due in part to autonomic innervation, are important in the maintenance of atrial fibrillation (AF). We hypothesized that heterogeneous sympathetic denervation with phenol would create a milieu for sustained AF. Methods and Results-After the determination of baseline inducibility, 15 dogs underwent atrial epicardial phenol application and 11 underwent a sham procedure. After 2 weeks of recovery, the animals had repeat attempts at inducing AF and effective refractory period (ERP) testing. Epicardial maps were obtained to determine local AF cycle lengths. ERPs were determined at baseline and during sympathetic, vagal, and simultaneous vagal/sympathetic stimulation.

Inducibility of atrial fibrillation during electrophysiologic evaluation is associated with increased dispersion of atrial refractoriness

“…Experimental studies also suggested that ERP dispersion is an important factor in determining the ability to sustain AF [24,25]. Our results showed that dispersion of refractoriness is a suitable indicator of atrial vulnerability for the induction of AF.…”

Atrial Fibrillation Produced by Prolonged Rapid Atrial Pacing Is Associated With Heterogeneous Changes in Atrial Sympathetic Innervation

“…21,22 However, in recent studies we found that heterogeneous sympathetic denervation of the atria with the epicardial application of phenol in dogs resulted in increased heterogeneity of atrial refractoriness and a milieu for sustained AF. 12 In the present study, we found that heterogeneity of sympathetic innervation increases with prolonged rapid rates. We also found that this sympathetic heterogeneity is spatially related to heterogeneity of atrial refractoriness (as reflected by AFCL).…”

“…The feasibility and methods of using [C-11]-labeled hydroxyephedrine (HED) to label atrial sympathetic nerve terminals have been previously described by our group. 12,14 HED was injected intravenously and arterial blood samples were drawn over a 30-minute period to calculate the available blood pool of HED. Two minutes before euthanasia, [F-18]-labeled microspheres of hydroxyapatite (20-to 40-m diameter) were injected into the left ventricular cavity and a continuous blood sample was drawn from the femoral artery at a predetermined rate to determine total atrial blood flow by the reference sample technique.…”

“…10,11 Recently we showed that heterogeneous atrial sympathetic denervation with epicardial phenol increases dispersion of atrial refractoriness and creates a substrate for sustained AF. 12 Whether changes in sympathetic innervation occur during electrophysiological remodeling of the atria and the mechanism by which these changes could alter atrial electrophysiology is unknown. We used a rapid atrial-paced canine model of AF to test the hypothesis that rapid atrial rates are accompanied by altered sympathetic innervation.…”

Differences in atrial fibrillation properties under vagal nerve stimulation versus atrial tachycardia remodeling

“…One of the characteristics of such remodeling is an increased heterogeneity in atrial refractoriness. Analogous to studies in ventricular arrhythmias, it has been proposed that a potential mechanism of such spatial dispersion of refractoriness could be the heterogeneity of autonomic innervation 99 . Thus, heterogeneous atrial denervation with application of phenol facilitated sustained AF in one study.…”