Pacing-induced spontaneous activity in myocardial sleeves of pulmonary veins after treatment with ryanodine.
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.


RESULTS
Extracellular potential mapping of rabbit right atrial preparations showed that ryanodine (2 micromol/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 micromol/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 beta-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.
Honjo
Haruo
H
Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan. honjo@riem.nagoya-u.ac.jp
Boyett
Mark R
MR
Niwa
Ryoko
R
Inada
Shin
S
Yamamoto
Mitsuru
M
Mitsui
Kazuyuki
K
Horiuchi
Toshiyuki
T
Shibata
Nitaro
N
Kamiya
Kaichiro
K
Kodama
Itsuo
I
D000200:Action Potentials; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology; D016275:Atrial Function / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D046508:Culture Techniques; D004594:Electrophysiology; D006325:Heart Atria / Q000033:anatomy & histology / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D011667:Pulmonary Veins; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013327:Strophanthidin / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D012433:Ryanodine; D013327:Strophanthidin; D007545:Isoproterenol; D002118:Calcium