Heterogeneous atrial denervation creates substrate for sustained atrial fibrillation

Background-Heterogeneous electrophysiological properties, which may be due in part to autonomic innervation, are important in the maintenance of atria l fibrillation (AF), We hypothesized that heterogeneous sympathetic denerva tion with phenol would create a milieu for sustained AF. Methods and Results-After the determination of baseline inducibility, 15 do gs underwent atrial epicardial phenol application and 11 underwent a sham p rocedure, After 2 weeks of recovery, the animals had repeat attempts at ind ucing AF and effective refractory period (ERP) testing. Epicardial maps wer e obtained to determine local AF cycle lengths. ERPs were determined at bas eline and during sympathetic, vagal, and simultaneous vagal/sympathetic sti mulation. Dogs then underwent PET imaging with either a sympathetic ([C-11] hydroxyephedrine, HED) or parasympathetic (5-[C-11]methoxybenzovesamicol, M OBV) nerve label. None of the animals had sustained AF (>60 minutes) at bas eline. None of the sham dogs and 14 of 15 phenol dogs had sustained AF at f ollow-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 m s) (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 stimulatio n 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 refractor iness (21+/-64 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 10 5+/-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 upta ke. Conclusions-Heterogeneous sympathetic atrial denervation with phenol facili tates sustained AF.