Treatment of rabbit pulmonary vein myocardial sleeves with ryanodine (0.5-2 micromol/L) induced spontaneous pacemaker activity and self-terminating bursts of action potentials after rapid pacing.
Does ryanodine treatment and rapid pacing induce spontaneous arrhythmogenic activity in rabbit pulmonary vein myocardial sleeves?
Pulmonary vein myocardial sleeves can generate spontaneous arrhythmogenic activity when intracellular calcium dynamics are modulated, providing mechanistic insight into focal triggers of atrial fibrillation.
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 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 et al. (Mon,) conducted a other in Atrial fibrillation mechanisms. Ryanodine vs. Control conditions was evaluated on Transmembrane potential and spontaneous activity. Treatment of rabbit pulmonary vein myocardial sleeves with ryanodine (0.5-2 micromol/L) induced spontaneous pacemaker activity and self-terminating bursts of action potentials after rapid pacing.