title: Autonomic innervation and segmental muscular disconnections at the human pulmonary vein-atrial junction: implications for catheter ablation of atrial-pulmonary vein junction.
abstract: OBJECTIVE
  This study sought to examine the muscle connections and autonomic nerve distributions at the human pulmonary vein (PV)-left atrium (LA) junction.
  
  
  BACKGROUND
  One approach to catheter ablation of atrial fibrillation (AF) is to isolate PV muscle sleeves from the LA. Elimination of vagal response further improves success rates.
  
  
  METHODS
  We performed immunohistochemical staining on 192 circumferential venoatrial segments (32 veins) harvested from 8 autopsied human hearts using antibodies to tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT).
  
  
  RESULTS
  Muscular discontinuities of widths 0.1 to 5.5 mm (1.1 +/- 1.0 mm) and abrupt 90 degrees changes in fiber orientation were found in 70 of 192 (36%) and 36 of 192 (19%) of PV-LA junctions, respectively. Although these anisotropic features were more common in the anterosuperior junction (p < 0.01), they were also present around the entire PV-LA junction. Autonomic nerve density was highest in the anterosuperior segments of both superior veins (p < 0.05 versus posteroinferior) and inferior segments of both inferior veins (p < 0.05 vs. superior), highest in the LA within 5 mm of the PV-LA junction (p < 0.01), and higher in the epicardium than endocardium (p < 0.01). Adrenergic and cholinergic nerves were highly co-located at tissue and cellular levels. A significant proportion (30%) of ganglion cells expressed dual adrenocholinergic phenotypes.
  
  
  CONCLUSIONS
  Muscular discontinuities and abrupt fiber orientation changes are present in >50% of PV-LA segments, creating significant substrates for re-entry. Adrenergic and cholinergic nerves have highest densities within 5 mm of the PV-LA junction, but are highly co-located, indicating that it is impossible to selectively target either vagal or sympathetic nerves during ablation procedures.
authors.affiliation: Division of Cardiology, Department of Medicine, Los Angeles, California, USA.
authors.forename: Alex Y
authors.initials: AY
authors.lastname: Tan
authors.forename: Hongmei
authors.initials: H
authors.lastname: Li
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wachsmann-Hogiu
authors.forename: Lan S
authors.initials: LS
authors.lastname: Chen
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Chen
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fishbein
mesh_terms: D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000601:surgery; D017776:Autonomic Pathways / Q000033:anatomy & histology*; D017115:Catheter Ablation; D005260:Female; D006325:Heart Atria / Q000033:anatomy & histology* / Q000294:innervation; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000033:anatomy & histology; D009206:Myocardium / Q000166:cytology; D011667:Pulmonary Veins / Q000033:anatomy & histology* / Q000294:innervation / Q000601:surgery