Induction of Atrial Fibrillation and Nerve Sprouting by Prolonged Left Atrial Pacing in Dogs

The authors hypothesized that rapid electrical stimulation can induce nerve sprouting in canine atria, and that LA pacing is more effective than RA pacing in inducing sustained AF. Chronic rapid (20 Hz) LA epicardial pacing was performed in six dogs. Sustained AF (>48 hours) was induced within 23 +/- 8 days, which was much faster than that with RA endocardial pacing using the same protocol (139 +/- 84 days, P < 0.05). Nerves were identified by immunocytochemical techniques. In all dogs, growth-associated protein 43-positive (sprouting) nerve density was highest near the pacing site, and the rapid LA pacing resulted in differential nerve sprouting among the LA, left superior pulmonary vein (LSPV), interatrial septum (IAS), and RA (5521 +/- 1496, 3154 +/- 2355, 3953 +/- 1164, 1559 +/- 1077 microm2/mm2, respectively, P = 0.0032). Tyrosine hydroxylase-positive (sympathetic) nerve density were not significantly different among groups (2726 +/- 1165, 1586 +/- 558, 2156 +/- 1741, 1509 +/- 1242 microm2/mm2, respectively). The nerves were inhomogeneously distributed. LA epicardial pacing induced sustained AF much faster than RA endocardial pacing and rapid electrical stimulation can induce inhomogeneous nerve sprouting near the pacing site.