Key result
Acetylcholine shortens pulmonary vein refractoriness, enabling induction of stable re-entrant tachycardias.
Why the study?
The mechanisms of rapid repetitive discharges from the pulmonary vein initiating paroxysmal atrial fibrillation remain incompletely understood.
Does acetylcholine induce re-entrant tachycardias in canine pulmonary vein sleeves?
Does acetylcholine induce re-entrant tachycardias in canine pulmonary vein sleeves?
Elevated parasympathetic tone combined with heterogeneity of electrophysiological properties in pulmonary veins creates a favorable substrate for rapid and stable re-entry, potentially driving paroxysmal atrial fibrillation.
Acetylcholine enables stable PV reentry in canine models; leaves open whether parasympathetic tone drives clinical paroxysmal AF.
OBJECTIVES: We investigated the hypothesis that re-entrant pulmonary vein (PV) tachycardias may serve as a mechanism for initiating and sustaining paroxysmal atrial fibrillation (PAF). BACKGROUND: The mechanisms of rapid repetitive discharges from the PV initiating PAF remain incompletely understood. Pulmonary vein myocardial sleeves appear to provide a favorable substrate for re-entry formation. METHODS: The electrophysiologic properties of canine PV sleeves were investigated using a combination of high-resolution optical mapping (n = 5) and extracellular bipolar and intracellular microelectrode recordings (n = 56) in a superfused PV preparation. RESULTS: From the left atrium to distal PV, there was progressive shortening of the action potential (AP) duration, reduction in AP and bipolar electrogram amplitude, and depolarization of resting membrane potentials. Sustained PV tachycardias were induced exclusively in the presence of acetylcholine (10(-7) to 10(-6) mol/l, n = 12). Sustained PV tachycardias were rapid (mean cycle length = 93 +/- 15 ms), regular, and capable of induction, termination, and resetting by single extrastimuli. Re-entry as the mechanism underlying PV tachycardias was confirmed by optical mapping (n = 5). Acetylcholine also reduced the slope of the AP restitution curve and suppressed AP alternans (n = 6). Importantly, PV tachycardias exhibited 1:1 conduction into the atrium at short cycle lengths (<100 ms), emphasizing the potential role of re-entrant PV tachycardia in atrial fibrillation. CONCLUSIONS: Pulmonary veins provide a favorable substrate for re-entry formation. Heterogeneity of the electrophysiologic properties and marked abbreviation of action potential duration and refractoriness by acetylcholine combine to produce rapid and stable re-entrant PV tachycardias. Elevated parasympathetic tone and re-entrant PV tachycardia may serve as a mechanism underlying the perpetuation of PAF.
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Po et al. (2005) studied Paroxysmal Atrial Fibrillation (n=61). Acetylcholine vs. Absence of acetylcholine (basal conditions) was evaluated on Induction of sustained pulmonary vein tachycardias. Acetylcholine administration reduced action potential duration and refractoriness, exclusively enabling the induction of rapid and stable re-entrant pulmonary vein tachycardias.
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