CLINICAL RESEARCH
Autonomic Innervation and Segmental Muscular Disconnections at the Human Pulmonary Vein-Atrial Junction
Implications for Catheter Ablation of Atrial-Pulmonary Vein Junction
Alex Y. Tan, MD*,
Hongmei Li, MD*,
Sebastian Wachsmann-Hogiu, PhD ,
Lan S. Chen, MD ,
Peng-Sheng Chen, MD, FACC* and
Michael C. Fishbein, MD, FACC ,*
* Division of Cardiology, Department of Medicine
Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California
Division of Neurology, Department of Pediatrics, Los Angeles Children's Hospital and USC Keck School of Medicine, Los Angeles, California
Division of Anatomic Pathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California
Manuscript received October 6, 2005;
revised manuscript received February 1, 2006,
accepted February 7, 2006.
* Reprint requests and correspondence: Dr. Michael C. Fishbein, Department of Pathology and Laboratory Medicine, UCLA School of Medicine, Room 13-145H, 10833 Le Conte Avenue, Los Angeles, California 90095-1732 (Email: mfishbein{at}mednet.ucla.edu).
OBJECTIVES: This study sought to examine the muscle connections and autonomic nerve distributions at the human pulmonary vein (PV)-left atrium (LA) junction.
BACKGROUND: One approach to catheter ablation of atrial fibrillation (AF) is to isolate PV muscle sleeves from the LA. Elimination of vagal response further improves success rates.
METHODS: We performed immunohistochemical staining on 192 circumferential venoatrial segments (32 veins) harvested from 8 autopsied human hearts using antibodies to tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT).
RESULTS: Muscular discontinuities of widths 0.1 to 5.5 mm (1.1 ± 1.0 mm) and abrupt 90° changes in fiber orientation were found in 70 of 192 (36%) and 36 of 192 (19%) of PV-LA junctions, respectively. Although these anisotropic features were more common in the anterosuperior junction (p < 0.01), they were also present around the entire PV-LA junction. Autonomic nerve density was highest in the anterosuperior segments of both superior veins (p < 0.05 versus posteroinferior) and inferior segments of both inferior veins (p < 0.05 vs. superior), highest in the LA within 5 mm of the PV-LA junction (p < 0.01), and higher in the epicardium than endocardium (p < 0.01). Adrenergic and cholinergic nerves were highly co-located at tissue and cellular levels. A significant proportion (30%) of ganglion cells expressed dual adrenocholinergic phenotypes.
CONCLUSIONS: Muscular discontinuities and abrupt fiber orientation changes are present in >50% of PV-LA segments, creating significant substrates for re-entry. Adrenergic and cholinergic nerves have highest densities within 5 mm of the PV-LA junction, but are highly co-located, indicating that it is impossible to selectively target either vagal or sympathetic nerves during ablation procedures.
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Abbreviations and Acronyms
| | AF = atrial fibrillation | | ChAT = anticholine acetyltransferase | | LA = left atrium | | LIPV = left inferior pulmonary vein | | LSPV = left superior pulmonary vein | | PV = pulmonary vein | | RF = radiofrequency | | RSPV = right superior pulmonary vein | | TH = antityrosine hydroxylase |
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