title: Shift in the pattern of autonomic atrial innervation in subjects with persistent atrial fibrillation.
abstract: BACKGROUND
  Atrial fibrillation (AF) is a multifactorial disease of the atria.
  
  
  OBJECTIVE
  We studied the differences in the atrial autonomic innervation pattern in subjects with AF compared with sinus rhythm (SR).
  
  
  METHODS
  Preparation of postmortem isolated hearts of subjects with documented persistent AF (group A) and SR (group B) included: (1) histological sectioning of predefined areas and quantification of nerve density, and (2) differentiation using immunohistochemistry in adrenergic (sympathetic, tyrosine-hydroxylase antibody), cholinergic (parasympathetic, choline-acetyltransferase antibody) and mixed (adrenergic and cholinergic staining) nerves.
  
  
  RESULTS
  Characteristics of subjects in group A (N = 15) and group B (N = 24) did not differ. The mean overall nerve density was similar between groups (A: 0.31 ± 0.25/mm(2); B: 0.35 ± 0.25/mm(2); P = .87). Nerve density appeared higher in the region of the pulmonary vein ostia and antrum (group A: 0.38 ± 0.21/mm(2); group B: 0.32 ± 0.19/mm(2),) compared with other locations of the right and left atrium. A total of 2,224 (group A: 685; group B: 1539) nerves were differentiated using immunohistochemistry. There was a high degree of colocalization of adrenergic and cholinergic nerves (group A: 80% mixed staining, group B: 69% mixed staining). In group A hearts there was a significantly lower density of predominantly cholinergic nerves (0.025 ± 0.052/mm(2) vs. 0.058 ± 0.099/mm(2); P = .008) and a higher density of nerves containing adrenergic components (0.24 ± 0.18/mm(2) vs. 0.18 ± 0.17/mm(2), P = .046).
  
  
  CONCLUSIONS
  Overall autonomic nerve density did not differ between atria with persistent AF compared with SR. On a morphological level, we detected a shift toward a lower density of cholinergic nerves and a higher density of nerves containing adrenergic components in AF subjects.
authors.affiliation: University Heart Center Bochum, Bergmannsheil, Germany. thomas.deneke@rub.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Deneke
authors.forename: Huda
authors.initials: H
authors.lastname: Chaar
authors.forename: Joris R
authors.initials: JR
authors.lastname: de Groot
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Wilde
authors.forename: Thomas
authors.initials: T
authors.lastname: Lawo
authors.forename: Johanna
authors.initials: J
authors.lastname: Mundig
authors.forename: Leif
authors.initials: L
authors.lastname: Bösche
authors.forename: Andreas
authors.initials: A
authors.lastname: Mügge
authors.forename: Peter H
authors.initials: PH
authors.lastname: Grewe
mesh_terms: D000320:Adrenergic Fibers; D000368:Aged; D001281:Atrial Fibrillation / Q000503:physiopathology*; D017776:Autonomic Pathways / Q000503:physiopathology*; D001344:Autopsy; D016022:Case-Control Studies; D002799:Cholinergic Fibers; D005260:Female; D006325:Heart Atria / Q000293:injuries*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male