PRECLINICAL STUDY
Rapid and Stable Re-Entry Within the Pulmonary Vein as a Mechanism Initiating Paroxysmal Atrial Fibrillation
Sunny S. Po, MD, PhD*,*,
Yuhua Li, PhD ,
David Tang, MS,
Hong Liu, PhD,
Ning Geng, MD ,
Warren M. Jackman, MD*,
Benjamin Scherlag, PhD*,
Ralph Lazzara, MD* and
Eugene Patterson, PhD
* Cardiac Arrhythmia Research Institute, Department of Medicine, Oklahoma City, Oklahoma
College of Engineering, School of Electrical and Computer Engineering, University of Oklahoma, Norman, Oklahoma
Cardiology Department, 2nd Affiliated Hospital of China Medical University, Shenyang, China
Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma
Manuscript received December 23, 2004;
revised manuscript received February 9, 2005,
accepted February 22, 2005.
* Reprint requests and correspondence: Dr. Sunny S. Po, 1200 Everett Drive, ET-6E103, Oklahoma City, Oklahoma 73104. (Email: sunny-po{at}ouhsc.edu).
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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Abbreviations and Acronyms
| | ACH = acetylcholine | | AF = atrial fibrillation | | APD = action potential duration | | CL = cycle length | | DI = diastolic interval | | DS = distal pulmonary vein sleeve | | LA = left atrium/atrial | | PS = proximal pulmonary vein sleeve | | PV = pulmonary vein | | Rt = steepest slope of the action potential restitution curve |
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