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(Circulation. 2005;111:2889-2897.)
© 2005 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Intracellular Calcium Dynamics and Anisotropic Reentry in Isolated Canine Pulmonary Veins and Left Atrium

Chung-Chuan Chou, MD; Motoki Nihei, MD; Shengmei Zhou, MD; Alex Tan, MD; Ayaka Kawase, MD; Edgar S. Macias, BS; Michael C. Fishbein, MD; Shien-Fong Lin, PhD; Peng-Sheng Chen, MD

From the Division of Cardiology (C.-C.C., M.N., S.Z., A.T., A.K., E.S.M., S.-F.L., P.-S.C.), Department of Medicine, Cedars-Sinai Medical Center, and the Division of Anatomical Pathology (M.C.F.), Department of Pathology, David Geffen School of Medicine, UCLA, Los Angeles, Calif.

Correspondence to Peng-Sheng Chen, MD, Room 5342, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048. E-mail chenp{at}cshs.org

Received August 9, 2004; revision received February 2, 2005; accepted February 9, 2005.

Background— Rapid activations due to either focal discharge or reentry are often present during atrial fibrillation (AF) in the pulmonary veins (PVs). The mechanisms of these rapid activations are unclear.

Methods and Results— We studied 7 isolated, Langendorff-perfused canine left atrial (LA) and PV preparations and used 2 cameras to map membrane potential alone (Vm, n=3) or Vm and intracellular calcium simultaneously (Ca_i, n=4). Rapid atrial pacing induced 26 episodes of focal discharge from the proximal PVs in 5 dogs. The cycle lengths were 223±52 ms during ryanodine infusion (n=13) and 133±59 ms during ryanodine plus isoproterenol infusion (n=13). The rise of Ca_i preceded Vm activation at the sites of focal discharge in 6 episodes of 2 preparations, compatible with voltage-independent spontaneous Ca_i release. Phase singularities during pacing-induced reentry clustered specifically at the PV-LA junction. Periodic acid-Schiff (PAS) stain identified large cells with pale cytoplasm along the endocardium of PV muscle sleeves. There were abrupt changes in myocardial fiber orientation and increased interstitial fibrosis in the PV and at the PV-LA junction.

Conclusions— PV muscle sleeves may develop voltage-independent Ca_i release, resulting in focal discharge. Focal discharge may also be facilitated by the presence of PAS-positive cells that are compatible with node-like cells. During reentry, phase singularities clustered preferentially at sites of increased anisotropy such as the PV-LA junction. These findings suggest that focal discharge caused by spontaneous calcium release and anisotropic reentry both contribute to rapid activations in the PVs during AF.

Key Words: fibrillation • imaging • calcium • mapping • anisotropy

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