Effects of Experimental Heart Failure on Atrial Cellular and Ionic Electrophysiology

Li, Danshi PhD
Melnyk, Peter MSc
Feng, Jianlin MSc
Wang, Zhiguo PhD
Petrecca, Kevin BSc
Shrier, Alvin PhD
Nattel, Stanley MD

From the Department of Medicine, Montreal Heart Institute and University of Montreal (D.L., J.F., Z.W., S.N.), and the Departments of Pharmacology (S.N.), Physiology (K.P., A.S.), and Pathology (P.M.), McGill University, Montreal, Quebec, Canada.

Received October 12, 1999;

revision received December 14, 1999; accepted December 22, 1999.

Correspondence to Dr Stanley Nattel, Research Center, Montreal Heart Institute, 5000 Belanger St E, Montreal, Quebec, Canada, H1T 1C8. E-mail [email protected]

Circulation 101(22):p 2631-2638, June 6, 2000.

Background

Congestive heart failure (CHF) is frequently associated with atrial fibrillation (AF), but little is known about the effects of CHF on atrial cellular electrophysiology.

Methods and Results

We studied action potential (AP) properties and ionic currents in atrial myocytes from dogs with CHF induced by ventricular pacing at 220 to 240 bpm for 5 weeks. Atrial myocytes from CHF dogs were hypertrophied (mean±SEM capacitance, 89±2 pF versus 71±2 pF in control, n=160 cells per group, P <0.001). CHF significantly reduced the density of L-type Ca²⁺ current (I_Ca) by ≈30%, of transient outward K⁺ current (I_to) by ≈50%, and of slow delayed rectifier current (I_Ks) by ≈30% without altering their voltage dependencies or kinetics. The inward rectifier, ultrarapid and rapid delayed rectifier, and T-type Ca²⁺ currents were not altered by CHF. CHF increased transient inward Na⁺/Ca²⁺ exchanger (NCX) current by ≈45%. The AP duration of atrial myocytes was not altered by CHF at slow rates but was increased at faster rates, paralleling in vivo refractory changes. CHF created a substrate for AF, prolonging mean AF duration from 8±4 to 535±82 seconds (P <0.01).

Conclusions

Experimental CHF selectively decreases atrial I_to, I_Ca, and I_Ks, increases NCX current, and leaves other currents unchanged. The cellular electrophysiological remodeling caused by CHF is quite distinct from that caused by atrial tachycardia, highlighting important differences in the cellular milieu characterizing different clinically relevant AF substrates.