Affiliation:
1. 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.
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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
319 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献