title: 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±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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiovascular Diseases, First Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Jiu Yang
authors.initials: JY
authors.lastname: Jiang
authors.forename: Xiu Fen
authors.initials: XF
authors.lastname: Qu
authors.forename: Guang
authors.initials: G
authors.lastname: Yu
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D054087:Atrial Septum / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002304:Cardiac Pacing, Artificial / Q000009:adverse effects; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism; D006321:Heart / Q000294:innervation; D006325:Heart Atria / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017764:Parasympathectomy / Q000009:adverse effects*; D013373:Substance P / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; D019922:GAP-43 Protein; D018377:Neurotransmitter Agents; D013373:Substance P