© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Atrial electrophysiological remodeling caused by rapid atrial activation: underlying mechanisms and clinical relevance to atrial fibrillation
Research Center and Department of Medicine, Montreal Heart Institute, the Department of Medicine, University of Montreal, and the Department of Pharmacology and Therapeutics, McGill University, 5000 Bélanger Street East, Montreal, Quebec H1T 1C8, Canada
nattel{at}icm.umontreal.ca
* Corresponding author. Tel.: +1-514-376-3330 ext. 3990; fax: +1-514-376-1355
One of the most exciting developments in our understanding of atrial fibrillation (AF) over the last several years has been the recognition that AF itself modifies atrial electrical properties in a way that promotes the occurrence and maintenance of the arrhythmia, a process termed ‘atrial remodeling’. The principle stimulus for AF-induced atrial remodeling is the rapid atrial rate that results: rapid regular atrial pacing produces changes similar to those caused by AF in animal models. The mechanisms of atrial tachycardia-induced remodeling have been extensively explored, and involve changes in atrial electrophysiology associated with altered ion channel function. The most important ionic change is a reduction in L-type Ca2+ current, which reduces action potential duration (APD) and APD adaptation to rate. AF-induced changes in ion channel function appear to be due both to rapid voltage- and time-dependent alterations in channel availability caused by tachycardia and to slower downregulation of messenger RNA concentrations encoding 
-subunits of specific ion channels. Atrial remodeling likely contributes importantly to a wide variety of clinical phenomena of previously unrecognized mechanism, including atrial dysfunction after cardioversion of AF, the increasing resistance to therapy of longer-standing AF, the association of AF with other forms of supraventricular tachyarrhythmia and the tendency of paroxysmal AF to become chronic. The present paper reviews the state of knowledge regarding the mechanisms and clinical consequences for AF of atrial remodeling caused by rapid atrial activation.
KEYWORDS Atrial fibrillation; Electrophysiological remodeling; Ion channels; Antiarrhythmic drugs; Electrophysiology of human heart; Electrocardiogram; Action potential
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