title: Dissociation between ionic remodeling and ability to sustain atrial fibrillation during recovery from experimental congestive heart failure.
abstract: BACKGROUND
  Congestive heart failure (CHF) downregulates atrial transient outward (I(to)), slow delayed rectifier (I(Ks)), and L-type Ca(2+) (I(Ca,L)) currents and upregulates Na(+)-Ca(2+) exchange current (I(NCX)) (ionic remodeling) and causes atrial fibrosis (structural remodeling). The relative importance of ionic versus structural remodeling in CHF-related atrial fibrillation (AF) is controversial.
  
  
  RESULTS
  We measured hemodynamic and echocardiographic parameters, mean duration of burst pacing-induced AF (DAF), and atrial-myocyte ionic currents in dogs with CHF induced by 2-week ventricular tachypacing (240 bpm), CHF dogs allowed to recover without pacing for 4 weeks (REC), and unpaced controls. Left ventricular ejection fraction averaged 58.6+/-1.2% (control), 36.2+/-2.3% (CHF, P<0.01), and 57.9+/-1.6% (REC), indicating full hemodynamic recovery. Similarly, left atrial pressures were 2.2+/-0.3 (control), 13.1+/-1.5 (CHF), and 2.4+/-0.4 (REC) mm Hg. CHF reduced I(to) density by approximately 65% (P<0.01), decreased I(Ca,L) density by approximately 50% (P<0.01), and diminished I(Ks) density by approximately 40% (P<0.01) while increasing I(NCX) density by approximately 110% (P<0.05). In REC, all ionic current densities returned to control values. DAF increased in CHF (1132+/-207 versus 14.3+/-8.8 seconds, control) and remained increased with REC (1014+/-252 seconds). Atrial fibrous tissue content also increased in CHF (2.1+/-0.2% for control versus 10.2+/-0.7% for CHF, P<0.01), with no recovery observed in REC (9.4+/-0.8%, P<0.01 versus control, P=NS versus CHF).
  
  
  CONCLUSIONS
  With reversal of CHF, there is complete recovery of ionic remodeling, but the prolonged-AF substrate and structural remodeling remain. This suggests that structural, not ionic, remodeling is the primary contributor to AF maintenance in experimental CHF.
authors.affiliation: 5000 Belanger St East, Montreal, Quebec, H1T 1C8, Canada. nattel@icm.umontreal.ca
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Cha
authors.forename: Joachim R
authors.initials: JR
authors.lastname: Ehrlich
authors.forename: Liming
authors.initials: L
authors.lastname: Zhang
authors.forename: Yan-Fen
authors.initials: YF
authors.lastname: Shi
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
authors.forename: Tack Ki
authors.initials: TK
authors.lastname: Leung
authors.forename: Stanley
authors.initials: S
authors.lastname: Nattel
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002478:Cells, Cultured; D051668:Delayed Rectifier Potassium Channels; D004285:Dogs; D004553:Electric Conductivity; D005355:Fibrosis; D006325:Heart Atria / Q000473:pathology; D006333:Heart Failure / Q000150:complications*; D006439:Hemodynamics; D007473:Ion Channels / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D019831:Sodium-Calcium Exchanger / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D051668:Delayed Rectifier Potassium Channels; D007473:Ion Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D019831:Sodium-Calcium Exchanger