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(Circulation. 2003;107:1937.)
© 2003 American Heart Association, Inc.

Basic Science Reports

Pacing-Induced Spontaneous Activity in Myocardial Sleeves of Pulmonary Veins After Treatment With Ryanodine

Haruo Honjo, MD; Mark R. Boyett, PhD; Ryoko Niwa, MD; Shin Inada, MEng; Mitsuru Yamamoto, MD; Kazuyuki Mitsui, PhD; Toshiyuki Horiuchi, PhD; Nitaro Shibata, MD; Kaichiro Kamiya, MD; Itsuo Kodama, MD

From RIEM, Nagoya University, Nagoya, Japan (H.H., R.N., M.Y., T.H., K.K., I.K.); School of Biomedical Sciences, University of Leeds, Leeds, UK (M.R.B.); School of Engineering, Tokyo Denki University, Tokyo, Japan (S.I., K.M.); and Tokyo Women’s Medical University, Tokyo, Japan (N.S.).

Correspondence to Dr Haruo Honjo, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan. E-mail honjo{at}riem.nagoya-u.ac.jp

Background— Recent clinical electrophysiology studies and successful results of radiofrequency catheter ablation therapy suggest that high-frequency focal activity in the pulmonary veins (PVs) plays important roles in the initiation and perpetuation of atrial fibrillation, but the mechanisms underlying the focal arrhythmogenic activity are not understood.

Methods and Results— Extracellular potential mapping of rabbit right atrial preparations showed that ryanodine (2 µmol/L) caused a shift of the leading pacemaker from the sinoatrial node to an ectopic focus near the right PV-atrium junction. The transmembrane potential recorded from the isolated myocardial sleeve of the right PV showed typical atrial-type action potentials with a stable resting potential under control conditions. Treatment with ryanodine (0.5 to 2 µmol/L) resulted in a depolarization of the resting potential and a development of pacemaker depolarization. These changes were enhanced transiently after an increase in the pacing rate: a self-terminating burst of spontaneous action potentials (duration, 33.6±5.0 s; n=32) was induced by a train of rapid stimuli (3.3 Hz) applied after a brief rest period. The pacing-induced activity was attenuated by either depletion of the sarcoplasmic reticulum of Ca²⁺ or blockade of the sarcolemmal Na⁺-Ca²⁺ exchanger or Cl^- channels and potentiated by ß-adrenergic stimulation.

Conclusions— PV myocardial sleeves have the potential to generate spontaneous activity, and such arrhythmogenic activity is uncovered by modulation of intracellular Ca²⁺ dynamics.

Key Words: electrophysiology • fibrillation • veins • action potentials

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