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. Dogs then underwent PET imaging with either a sympathetic ([11C]hydroxyephedrine, HED) or parasympathetic (5[11C]methoxybenzovesamicol, MOBV) nerve label. None of the animals had sustained AF (>60 minutes) at baseline. None of the sham dogs and 14 of 15 phenol dogs had sustained AF at follow-up. Sites to which phenol was applied had a significantly shorter ERP (136±17.6 ms) than those same sites in the sham controls (156±19.1 ms) (P=0.01). Although there was no difference in the ERP change with either vagal or sympathetic stimulation alone between phenol and nonphenol sites, the percent decrease in ERP with simultaneous vagal/sympathetic stimulation was greater in the phenol sites (17±8%) than in the nonphenol sites (9±9%) (P=0.01). There was a significantly increased dispersion of refractoriness (21±6.4 ms in the sham versus 58±14 ms in the phenol dogs, P=0.01) as well as dispersion of AF cycle length (49±10 ms in the Sham versus 105± 12 ms in the phenol dogs, P=0.0001). PET images demonstrated defects of HED uptake in the areas of phenol application, with no defect of MOBV uptake. Conclusions-Heterogeneous sympathetic atrial denervation with phenol facilitates sustained AF.