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(Circulation. 2005;111:728-735.)
© 2005 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Atrial Tachycardia Remodeling of Pulmonary Vein Cardiomyocytes

Comparison With Left Atrium and Potential Relation to Arrhythmogenesis

Tae-Joon Cha, MD; Joachim R. Ehrlich, MD; Liming Zhang, MSc; Denis Chartier, MSc; Tack Ki Leung, MD; Stanley Nattel, MD

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

Correspondence to Stanley Nattel, 5000 Belanger St, Montreal, Quebec, H1T 1C8, Canada. E-mail stanley.nattel{at}icm-mhi.org

Received May 19, 2004; revision received October 19, 2004; accepted November 3, 2004.

Background— The pulmonary veins (PVs) are important in the pathophysiology of atrial fibrillation (AF), as is atrial tachycardia (AT) remodeling. The relative importance of AT remodeling in PVs versus other atrial sites is unknown. The present study assessed AT-induced cellular changes in PVs versus left atrium (LA) and their relationship to arrhythmogenesis.

Methods and Results— We studied ionic currents (single-cell patch clamp) and action potentials (APs; coronary-perfused multicellular preparations) in the PVs and LA free wall of dogs after 7-day AT pacing (400 bpm), as well as in nonpaced control dogs. In controls, rapid (I_Kr) and slow (I_Ks) delayed-rectifier currents were larger in PVs; transient-outward (I_to), inward-rectifier (I_K1), and L-type Ca²⁺ (I_Ca) currents and AP duration were smaller. AT remodeling reduced I_Ca and I_to, left I_Kr and I_Ks unchanged, and increased I_K1 in both LA and PV. AT reduced action potential duration in both LA and PV. LA–PV AP differences became smaller in AT than in control dogs. Premature extrastimuli induced atrial tachyarrhythmias at 4.5±2.8% (mean±SEM) sites in 6 control multicellular preparations compared with 64.2±7.3% sites in 9 AT-remodeled preparations (P<0.001). Resection of all PVs failed to alter atrial tachyarrhythmia inducibility in AT-remodeled preparations (67.5±13.1%). PV resection did not significantly change tachyarrhythmia duration (mean 3.9 seconds per heart, range 0.7 to 15.7 seconds before resection; mean 7.0 seconds per heart, range 0.9 to 36.0 seconds after resection) or cycle length (120±6 ms before resection, 115±8 ms after resection).

Conclusions— AT produces qualitatively similar ionic remodeling in LA and PVs but reduces PV–LA AP differences. PVs are not essential for AT-induced atrial tachyarrhythmia promotion in this model, which may relate to the failure of PV isolation to prevent AF in some patient populations.

Key Words: ion channels • atrium • fibrillation

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