title: Left-to-right gradient of atrial frequencies during acute atrial fibrillation in the isolated sheep heart.
abstract: BACKGROUND
  Recent studies demonstrated spatiotemporal organization in atrial fibrillation (AF). We hypothesized that waves emanating from sources in the left atrium (LA) undergo fragmentation, resulting in left-to-right frequency gradient. Our objective was to characterize impulse propagation across Bachmann's bundle (BB) and the inferoposterior pathway (IPP) during AF.
  
  
  RESULTS
  In 13 Langendorff-perfused sheep hearts, AF was induced in the presence of acetylcholine (ACh). Fast Fourier transform of optical and bipolar electrode recordings was performed. Frequency-dependent changes in the left-to-right dominant frequency (DF) gradient were studied by perfusing D600 (2 micromol/L) and by increasing ACh concentration from 0.2 to 0.5 micromol/L. BB and IPP were subsequently ablated. At baseline, a left-to-right decrease in DFs occurred along BB and IPP, resulting in an LA-right atrium (RA) frequency gradient of 5.7+/-1.4 HZ: Left-to-right impulse propagation was present in 81+/-5% and 80+/-10% of cases along BB and IPP, respectively. D600 decreased the highest LA frequency from 19.7+/-4.4 to 16.2+/-3.9 Hz (P<0.01) and raised RA DF from 8.6+/-2.0 to 10.7+/-1.8 Hz (P<0.05). An increase in ACh concentration increased the LA-RA frequency gradient from 4.9+/-1.8 to 8.9+/-1.8 Hz (P<0.05). Ablation of BB and IPP decreased RA DF from 10.9+/-1.2 to 9.0+/-1.5 Hz (P<0.01) without affecting LA DF (16.8+/-1.5 versus 16.9+/-1.8 Hz, P=NS).
  
  
  CONCLUSIONS
  Left-to-right impulse propagation and frequency-dependent changes in the LA-RA frequency gradient during AF strongly support the hypothesis that this arrhythmia is the result of high-frequency periodic sources in the LA, with fibrillatory conduction away from such sources.
authors.affiliation: Departments of Pharmacology, SUNY Upstate Medical University, Syracuse, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Mansour
authors.forename: R
authors.initials: R
authors.lastname: Mandapati
authors.forename: O
authors.initials: O
authors.lastname: Berenfeld
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: F H
authors.initials: FH
authors.lastname: Samie
authors.forename: J
authors.initials: J
authors.lastname: Jalife
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000208:Acute Disease; D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005711:Gallopamil / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology*; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D012756:Sheep; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D005711:Gallopamil; D000109:Acetylcholine