PRECLINICAL STUDY
Unique Autonomic Profile of the Pulmonary Veins and Posterior Left Atrium
Rishi Arora, MD,
Jason Ng, PhD,
Joseph Ulphani, MD,
Ilias Mylonas, MD,
Haris Subacius, PhD,
Greg Shade, BS,
David Gordon, MD, PhD,
Alexander Morris, BS,
Xiang He, MS,
Yi Lu, MD,
Rashad Belin, PhD,
Jeffrey J. Goldberger, MD and
Alan H. Kadish, MD*
Division of Cardiology and Department of Medicine, Northwestern University-Feinberg School of Medicine, Chicago, Illinois.
Manuscript received May 9, 2006;
revised manuscript received October 23, 2006,
accepted October 29, 2006.
* Reprint requests and correspondence: Dr. Alan H. Kadish, Northwestern Memorial Hospital, 251 East Huron, Feinberg 8-542, Chicago, Illinois 60611. (Email: a-kadish{at}northwestern.edu).
Objectives: The purpose of this study was to investigate the electrophysiologic profile of the pulmonary veins (PVs) and left atrium (LA) in response to autonomic manipulation.
Background: The parasympathetic innervation of the PVs and posterior left atrium (PLA) is thought to contribute to focal atrial fibrillation (AF). We hypothesized that autonomic effects would be more prominent in these regions.
Methods: In 14 dogs, epicardial mapping was performed in the PVs, PLA, and left atrial appendage (LAA) under the following conditions: baseline, 20-Hz cervical vagal stimulation (VS), propranolol (P), P + VS, and P + atropine. Effective refractory periods (ERPs) were measured, and conduction vectors were computed at multiple sites. Western blotting and immunostaining were performed for IKAch (Kir3.1/3.4).
Results: The VS and P + VS caused more ERP shortening in the PV and PLA than in the LAA. The P + atropine caused greatest ERP prolongation in the LAA. Cumulative ERP change (ERP difference between P + VS and P + atropine) was greatest in the LAA and corresponded with expression of Kir3.1/3.4 (LAA > PLA  PV). The ERP change in response to vagal manipulation was most heterogeneous in the PLA; this corresponded with a pronounced heterogeneity of Kir3.1 distribution in the PLA. With VS and/or P, there was evidence of regional conduction delay in the PVs with a significant change in activation direction. Similar activation changes were not seen in the PLA and LAA.
Conclusions: The PVs and PLA demonstrate unique activation and repolarization characteristics in response to autonomic manipulation. The heterogeneity of vagal responses correlates with the pattern of IKAch distribution in the LA. The peculiar autonomic characteristics of the PVs and PLA might create substrate for re-entry and AF.
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Abbreviations and Acronyms
| | AF = atrial fibrillation | | ATR = atropine | | ERP = effective refractory period | | LA = left atrium | | LAA = left atrial appendage | | P = propranolol | | PLA = posterior left atrium | | PV = pulmonary vein | | VS = vagal stimulation |
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