Evidence for Increased Atrial Sympathetic Innervation in Persistent Human Atrial Fibrillation

OBJECTIVE: In this study, we aimed to compare the level of atrial sympathetic innervation in human atrial fibrillation (AF) to that in sinus rhythm (SR). BACKGROUND: Histological studies of atrial tissue obtained from animals with experimentally induced AF indicate that sympathetic hyperinnervation could play a role in the pathogenesis of AF. METHODS: In 24 patients (12 in SR and 12 in AF) undergoing bypass surgery, we collected right atrial appendage tissue. In AF patients, left atrial appendage tissue was also acquired. The degree of sympathetic innervation was quantified by measuring the amount of staining for tyrosine hydroxylase (TH) and tissue norepinephrine (NE). In conjunction, nerve growth factor (NGF) mRNA expression was assessed by real-time polymerase chain reaction (PCR). Growth-associated protein 43 (GAP43) immunostaining was used to assess degree of new neural growth. RESULTS: When corrected for differences in tissue fibrosis, the expression of both TH (AF 0.45 +/- 0.1%, SR 0.09 +/- 0.03%, P = 0.02) and tissue NE (AF 358 +/- 49 pg/mg, SR 225 +/- 39 pg/mg, P = 0.04) was greater in atrial tissue of the AF cohort. The degree of atrial TH staining (P = 0.01) and NE content (P < 0.001) was also significantly greater in the right compared with left atrial samples in the AF cohort. There were no differences in NGF mRNA expression or GAP43 staining. CONCLUSION: This study provides evidence for the presence of heightened atrial sympathetic innervation in patients with persistent AF, suggesting autonomic remodeling may be part of atrial substrate for AF.