Parasympathetic and substance P-immunoreactive nerve denervation in atrial fibrillation models.

Abstract

BACKGROUND: Recent studies demonstrated that atrial fibrillation (AF) induced heterogeneous sympathetic hyperinnervation and baroreflex impartation, but the changes of vagal and afferent nerve are not clear. METHODS: Six dogs underwent atrial pacing at 600 beats/min (AF group). All paced dogs developed sustained AF by 5 weeks of pacing. Tissues from six healthy dogs were used as controls. Immunohistochemistry staining of cardiac nerves was performed using anti-growth-associated protein 43 (anti-GAP43), anti-tyrosine hydroxylase, antiacetylcholine (anti-ACh), and anti-substance P (anti-SP) antibodies. RESULTS: In AF group, the density of GAP43-positive in the right atrium (RA), atrial septum (AS), and left atrium (LA) was 5590.24&#xb1;1417.51, 8083.22&#xb1;1271.39, and 10854.56&#xb1;1877.56 &#x3bc;m(2)/mm(2), respectively, which was significantly (P<.01) higher than the control group. Most of the newly sprouting nerves are sympathetic nerve. Sympathetic nerve density in AF group was significantly higher than that of control group (P<.001). Whereas denervation of parasympathetic and SP-immunoreactive nerve occurred in AF group. In the dogs with AF, the density of ACh-positive nerve in the RA, AS, and LA was 506.04&#xb1;104.44, 317.72&#xb1;84.10, and 114.9&#xb1;29. 62 &#x3bc;m(2)/mm(2), respectively, which was lower than the control group (P<.01). At the same time, the density of SP-positive nerve in the atria of AF dogs was also significantly lower than the control tissues (P<.01). CONCLUSION: AF led to significant nerve sprouting and sympathetic hyperinnervation in the canine models, but the newly sprouting nerve did not include parasympathetic and SP-immunoreactive nerve. Heterogeneous parasympathetic and SP-immunoreactive nerve denervation occurred in the AF dogs.