Different effects of norepinephrine and nerve growth factor on atrial fibrillation vulnerability. Issue 5 (November 2019) - Yang, Mei
Highlights: Nerve growth factor increases atrial fibrillation (AF) vulnerability. Norepinephrine decreases atrial hyperinnervation. Norepinephrine increases the incidence of AF and its duration. Ionic remodeling provides important substrates for AF vulnerability. Sympathetic hyperinnervation has no strong association with AF induction. Abstract: Background: The sympathetic nerve plays an important role in atrial fibrillation (AF) vulnerability. Norepinephrine (NE) has a relationship with AF and nerve growth factor (NGF) injection can induce sympathetic innervation. However, the mechanisms of NE and NGF on AF vulnerability remain unclear. Methods: Four groups of rabbits were studied: the control group, the NGF group, the NE group, and the NGF + valsartan + metoprolol group. After receiving drugs for 15 days, induced AF was observed, and left atrium (LA) tissues were obtained. Immunocytochemical staining of cardiac nerves and ionic remodeling were performed using anti–growth-associated protein 43 (GAP43), anti-tyrosine hydroxylase (TH) antibodies, and patch clamp. Results: The incidence of AF was significantly higher ( p < 0.01) in the NGF group and the NE group than in the control group and the NGF + valsartan + metoprolol group. The nerve densities for TH and GAP43-positive at the LA were significantly higher ( p < 0.01) after NGF, but the nerve densities decreased after NE. ICa, L was increased while instant outward K+ channel current (Ito) was decreased in the LA of rabbits after treatment with NGF and NE. Metoprolol and valsartan can reverse the ICa, L and Ito remodeling and the vulnerability to AF. However, these drugs did not inhibit the effect of NGF on sympathetic sprouting. Conclusions: The effects of NE and NGF on AF vulnerability have a relationship with the ionic remodeling, while the sympathetic hyperinnervation did not have a strong association with the induction of AF.