Dissociation between ionic remodeling and ability to sustain atrial fibrillation during recovery from experimental congestive heart failure.
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.
Cha
Tae-Joon
TJ
5000 Belanger St East, Montreal, Quebec, H1T 1C8, Canada. nattel@icm.umontreal.ca
Ehrlich
Joachim R
JR
Zhang
Liming
L
Shi
Yan-Fen
YF
Tardif
Jean-Claude
JC
Leung
Tack Ki
TK
Nattel
Stanley
S
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
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