Atrial Tachycardia Remodeling of Pulmonary Vein Cardiomyocytes

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Abstract
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 Ca 2+ ( 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 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.