title: Activation of inward rectifier potassium channels accelerates atrial fibrillation in humans: evidence for a reentrant mechanism.
abstract: BACKGROUND
  It is unclear whether atrial fibrillation (AF) drivers in humans are focal or reentrant. To test the hypothesis that functional reentry is involved in human AF maintenance, we determined the effects of adenosine infusion on local dominant frequency (DF) at different atrial sites. By increasing inward rectifier potassium channel conductance, adenosine would increase DF of reentrant drivers but decrease it in the case of a focal mechanism.
  
  
  RESULTS
  Thirty-three patients were studied during AF (21 paroxysmal, 12 persistent) using recordings from each pulmonary vein-left atrial junction (PV-LAJ), high right atrium, and coronary sinus. DFs were determined during baseline and peak adenosine effect. In paroxysmal AF, adenosine increased maximal DF at each region compared with baseline (PV-LAJ, 8.03+/-2.2 versus 5.7+/-0.8; high right atrium, 7+/-2.2 versus 5.4+/-0.7; coronary sinus, 6.6+/-1.1 versus 5.3+/-0.7 Hz; P=0.001) and increased the left-to-right DF gradient (P=0.007). In contrast, in persistent AF, adenosine increased DF only in the high right atrium (8.33+/-1.1 versus 6.8+/-1.2 Hz; P=0.004). In 4 paroxysmal AF patients, real-time DF mapping of the left atrium identified the highest DF sites near the PV-LAJ, where adenosine induced an increase in DF (6.7+/-0.29 versus 4.96+/-0.26 Hz; P=0.008). Finally, simulations demonstrate that the frequency of reentrant drivers accelerates proportionally to the adenosine-modulated inward rectifier potassium current.
  
  
  CONCLUSIONS
  Adenosine accelerates drivers and increases frequency differently in paroxysmal compared with persistent human AF. The results strongly suggest that AF is maintained by reentrant sources, most likely located at the PV-LAJ in paroxysmal AF, whereas non-PV locations are more likely in persistent AF.
authors.affiliation: Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: Atienza
authors.forename: Jesús
authors.initials: J
authors.lastname: Almendral
authors.forename: Javier
authors.initials: J
authors.lastname: Moreno
authors.forename: Ravi
authors.initials: R
authors.lastname: Vaidyanathan
authors.forename: Arkazdi
authors.initials: A
authors.lastname: Talkachou
authors.forename: Jérôme
authors.initials: J
authors.lastname: Kalifa
authors.forename: Angel
authors.initials: A
authors.lastname: Arenal
authors.forename: Julian P
authors.initials: JP
authors.lastname: Villacastín
authors.forename: Esteban G
authors.initials: EG
authors.lastname: Torrecilla
authors.forename: Ana
authors.initials: A
authors.lastname: Sánchez
authors.forename: Robert
authors.initials: R
authors.lastname: Ploutz-Snyder
authors.forename: José
authors.initials: J
authors.lastname: Jalife
authors.forename: Omer
authors.initials: O
authors.lastname: Berenfeld
mesh_terms: D000241:Adenosine / Q000502:physiology*; D000328:Adult; D001281:Atrial Fibrillation / Q000503:physiopathology* / Q000601:surgery; D017115:Catheter Ablation; D003198:Computer Simulation; D004594:Electrophysiology; D005260:Female; D006325:Heart Atria / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000502:physiology*; D011667:Pulmonary Veins / Q000503:physiopathology; D012849:Sinoatrial Node / Q000503:physiopathology; D013614:Tachycardia, Paroxysmal / Q000503:physiopathology
chemical_list: D024661:Potassium Channels, Inwardly Rectifying; D000241:Adenosine