Nerve sprouting induced by radiofrequency catheter ablation in dogs

Objectives: The purpose of this study was to test the hypothesis that radiofrequency (RF) catheter ablation results in cardiac nerve sprouting. Background: Nerve sprouting plays a role in cardiac arrhythmogenesis. Whether or not nerve sprouting occurs after RF catheter ablation is unclear. Methods: We performed RF catheter ablation in the right atrium (RA) and right ventricle (RV) in 10 dogs, which then were sacrificed in 2 hours (acute group, n = 5) or 1 month (chronic group, n = 5). Seven normal dogs were used as control. Immunohistochemical staining for growth-associated protein 43 (GAP-43) was performed to measure growing (sprouting) nerves. Results: A significant increase of GAP-43 immunoreactive nerve fiber density was observed at the RA ablation sites in 2 hours (4,410 ± 1,379 μm²/mm²) and in 1 month (2,948 ± 666 μm²/mm²) after ablation compared to controls (1,377 ± 471 μm²/mm², P = .0001). At remote sites (>2 cm away from ablation sites) of RA, RF ablation also resulted in robust nerve sprouting in both the acute group (5,846 ± 3241 μm²/mm²) and the chronic group (6,030 ± 2226 μm²/mm²). RF ablation in the RV did not increase nerve density at the ablation sites, but nerve density was increased at remote sites in 2 hours (1,345 ± 451 μm²/mm², P = .0136) that was reduced down to the normal control level (722 ± 337 μm²/mm²) in 1 month. Conclusions: Nerve sprouting occurred within 2 hours after RF ablation in both the RA and RV and persisted for at least 1 month in the RA but not the RV. The increased GAP-43⁺ nerve densities developed at both the ablation and the remote sites.