Abstract 1255: Sustained Atrial Fibrillation Increases Cardiac Sympathetic and Vagal Nerve Activity and Leads to Neural Remodeling of the Atria and Stellate Ganglion
Background. Nerve sprouting and sympathetic hyperinnervation are characteristics of the canine model of chronic atrial fibrillation (AF) induced by rapid atrial pacing. The mechanism of nerve sprouting and the patterns of cardiac sympathetic and vagal nerve activity during AF in this model remain undetermined.
Methods. We induced sustained AF by rapid left atrial (LA) pacing (20Hz) in 7 ambulatory dogs, and simultaneously recorded nerve activity directly from the left stellate ganglion (SGNA), superior cardiac branch of the left vagal nerve (VNA) and LA continuously (24 hr/d) for 6±2 weeks using a data sciences international radiotransmitter. Coronary sinus (CS) and aortic (AO) blood were sampled for norepinephrine (NE) and Nerve Growth Factor (NGF) ELISA assay. Tissues were immunostained for Tyrosine Hydroxylase (TH) and synaptophysin (SYN).
Results. Sustained (>48hrs) AF was induced after 4±2 weeks of rapid atrial pacing. Compared to baseline sinus rhythm (SR), sustained AF increased daily averaged SGNA (5.92±2.58 mV to 7.01±3.54 mV p<.05) and VNA (1.05±0.46 to 1.42±0.56 mV p<.05). There was a rise in transcardiac (CS-AO) NGF levels (−1.6±2.1 to 2.6±2.6ng/ml, p<.02 ) indicating augmented cardiac release of NGF. This was associated with nerve sprouting in the atria (TH immunoreactivity, 4249±1198 vs 1521±488μm2/mm2 normal controls p<.05) and LSG (SYN immunoreactivity 26171±5508 vs 8535±4513 μm2/mm2 p<.01), and an increase in transcardiac NE levels at rest (0.13±0.36 to 2.23±1.30 ng/ml, p<.05) and with LSG stimulation (1.75±0.56 to 12.11±4.58 ng/ml, p<.01). In all dogs, sustained AF spontaneously converted to SR in 5±3 days. After SR resumed, there was an increased incidence of paroxysmal AF (0 vs 4±1 episodes/d, 3/7dogs) and paroxysmal atrial tachycardia (2±2 vs 10±3 episodes/d), preceded by significantly increased SGNA and/or VNA in 96% of episodes (n=100).
Conclusions. Sustained induced AF is associated with increased transcardiac NGF expression, heightened cardiac sympathetic and vagal activity, sympathetic nerve sprouting and augmented cardiac NE release. These findings indicate that the newly sprouted sympathetic nerve endings are functionally active and contributed to the development of paroxysmal AF and AT after the resumption of SR.