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(Circulation. 2004;109:412-418.)
© 2004 American Heart Association, Inc.

Basic Science Reports

Dissociation Between Ionic Remodeling and Ability to Sustain Atrial Fibrillation During Recovery From Experimental Congestive Heart Failure

Tae-Joon Cha, MD; Joachim R. Ehrlich, MD; Liming Zhang, MSc; Yan-Fen Shi, MD; Jean-Claude Tardif, MD; Tack Ki Leung, MD; Stanley Nattel, MD

From the Departments of Medicine (T.J.C., J.R.E., L.Z., Y.F.S., J.C.T., S.N.) and Pathology (T.K.L.), Montreal Heart Institute and University of Montreal, Montreal, Quebec, Canada.

Correspondence to Stanley Nattel, 5000 Belanger St East, Montreal, Quebec, H1T 1C8, Canada. E-mail nattel{at}icm.umontreal.ca

Received July 28, 2003; revision received September 23, 2003; accepted September 25, 2003.

Background— Congestive heart failure (CHF) downregulates atrial transient outward (I_to), slow delayed rectifier (I_Ks), and L-type Ca²⁺ (I_Ca,L) currents and upregulates Na⁺-Ca²⁺ 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.

Methods and 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 65% (P<0.01), decreased I_Ca,L density by 50% (P<0.01), and diminished I_Ks density by 40% (P<0.01) while increasing I_NCX density by 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.

Key Words: heart failure • ion channels • atrium • fibrillation

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