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

Cardiovasc Pathol. 2012 Jan-Feb;21(1):39-45. doi: 10.1016/j.carpath.2011.01.003. Epub 2011 Feb 24.

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±1417.51, 8083.22±1271.39, and 10854.56±1877.56 μm(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±104.44, 317.72±84.10, and 114.9±29. 62 μm(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.

MeSH terms

  • Animals
  • Atrial Fibrillation / etiology
  • Atrial Fibrillation / metabolism
  • Atrial Fibrillation / pathology*
  • Atrial Septum / innervation
  • Atrial Septum / metabolism
  • Atrial Septum / pathology
  • Biomarkers / metabolism
  • Cardiac Pacing, Artificial / adverse effects
  • Disease Models, Animal
  • Dogs
  • Female
  • GAP-43 Protein / metabolism
  • Heart / innervation
  • Heart Atria / innervation
  • Heart Atria / metabolism
  • Heart Atria / pathology
  • Male
  • Neurons / metabolism
  • Neurons / pathology
  • Neurotransmitter Agents / metabolism*
  • Parasympathectomy / adverse effects*
  • Substance P / metabolism*
  • Sympathetic Nervous System / metabolism
  • Sympathetic Nervous System / pathology

Substances

  • Biomarkers
  • GAP-43 Protein
  • Neurotransmitter Agents
  • Substance P