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(Circulation Research. 2004;94:1403.)
© 2004 American Heart Association, Inc.

Editorials

Defining "Culprit Mechanisms" in Arrhythmogenic Cardiac Remodeling

Stanley Nattel

From the Department of Medicine, Montreal Heart Institute, University of Montreal, and Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.

Correspondence to Dr Stanley Nattel, Montreal Heart Institute, 5000 Belanger St E, Montreal, Quebec H1T 1C8, Canada. E-mail nattel@icm.umontreal.ca

Key Words: atrial fibrillation • cardiac ion channels • heart rhythm disorders • antiarrhythmic drug therapy

An extract of the first 250 words of the full text is provided, because this article has no abstract.

There has been increasing awareness of the importance of arrhythmogenic remodeling in the pathophysiology of cardiac arrhythmias.^1–3 Arrhythmogenic remodeling, involving acquired changes in cardiac structure or function that promote the occurrence of cardiac arrhythmias, occurs in a wide variety of paradigms including congestive heart failure (CHF), atrial fibrillation (AF), hypertensive cardiac disease, acute myocardial infarction, and valvular heart disease. In many of these contexts, changes occur at many levels: ion-channel density, distribution, and function; ion-transporter (pumps and exchanges) function; connexin-protein density and distribution; tissue and cell structure; and cardiac-chamber dimension and shape. Progress in the identification of such changes has been impressive: in some cases, hundreds of alterations have been described in response to single well-defined experimental paradigms. A major resulting challenge is to determine which changes are particularly central to the pathophysiology of remodeling-related arrhythmias, and to establish therapeutic implications. In the present issue of Circulation Research, Verheule et al take advantage of a unique transgenic mouse model to address this issue.⁴

Potential Role of Fibrosis in AF

Interstitial fibrosis has been associated with AF since at least the 1960s.⁵ Recent studies have demonstrated an association between atrial fibrous-tissue content, conduction abnormalities, and propensity to AF in animals with CHF,⁶ mitral regurgitation,^7,8 and senescence.^9,10 These observations point toward fibrosis-induced conduction abnormalities as promoters of local reentry^11,12 and thereby AF. However, the evidence has been predominantly circumstantial. Other mechanisms, such as delayed afterdepolarization-related triggered activity,¹³ favored by the Na⁺-Ca²⁺ exchanger upregulation that occurs in CHF,¹⁴ could also play a prominent role.

Verheule et al⁴ . . . [Full Text of this Article]

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