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June 6, 2000Circulation374 citations

Effects of Experimental Heart Failure on Atrial Cellular and Ionic Electrophysiology

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DLDanshi LiPMPeter MelnykJFJianlin Feng

Key Result

Experimental CHF in dogs selectively decreased atrial Ito, ICa, and IKs, increased NCX current, and prolonged mean AF duration from 8 to 535 seconds (P<0.01).

Structured PICO

Does experimental congestive heart failure alter action potential properties and ionic currents in atrial myocytes?

P
Population
Atrial myocytes from dogs with congestive heart failure (CHF) induced by ventricular pacing at 220 to 240 bpm for 5 weeks (n=160 cells per group)
I
Intervention
Experimental congestive heart failure (CHF) induced by ventricular pacing
C
Comparator
Control (atrial myocytes from dogs without CHF)
O
Outcome
Action potential (AP) properties and ionic currents in atrial myocytessurrogate

Experimental heart failure induces distinct cellular electrophysiological remodeling in atrial myocytes, creating a substrate for atrial fibrillation.

Main Result

Absolute Event Rate: 535% vs 8%

p-value: p=<0.01

Abstract

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 Ca 2+ 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 Ca 2+ currents were not altered by CHF. CHF increased transient inward Na + /Ca 2+ 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.

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Cite This Study

Li et al. (2000) studied Congestive heart failure. Experimental congestive heart failure vs. Control was evaluated on Mean AF duration (seconds) (p=<0.01). Experimental CHF in dogs selectively decreased atrial Ito, ICa, and IKs, increased NCX current, and prolonged mean AF duration from 8 to 535 seconds (P<0.01).

synapsesocial.com/papers/6a0f3cba04e2b0ba896cb93ahttps://doi.org/10.1161/01.cir.101.22.2631
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