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
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Figure 1 Patterns of pulmonary vein (PV)-left atrium (LA) connections. (A) Three patterns of PV-LA connections, from disconnected (Pattern 1) to well connected (Pattern 3). (B) Circumferential distributions.
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Figure 2 Circumferential distributions of muscular discontinuities and fiber orientations at the pulmonary vein (PV)-left atrium (LA) junction. (A1) The PV-LA gap (dotted line segment). (A2) Mean length of the PV-LA gap. (A3) Circumferential distribution of disconnected segments. (B1, B2) Two examples of abrupt reduction in muscle sleeve thickness at the PV-LA junction. (B3) The extent of reductions in muscle sleeve thickness at the anterosuperior versus posteroinferior junctions. (C1) Abrupt 90° changes in fiber direction at the PV-LA junction. (C2) High-power view of the boxed area in C1. (C3) Distribution of segments with this pattern. LIPV = left inferior pulmonary vein; LSPV = left superior pulmonary vein; RIPV = right inferior pulmonary vein; RSPV = right superior pulmonary vein.
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Figure 3 Examples of immunohistochemical staining results in cardiac ganglia and nerves. (A) Growth-associated protein 43 (GAP 43) demonstrating axonal growth within the ganglion; (B) synaptophysin (SYN) staining demonstrating synaptic endings; (C) neurofilament (NF) staining confirming the presence of nerve fibers; (D) choline acetyltransferase (ChAT) staining showing cholinergic nature of most ganglion cells; (E) tyrosine hydroxylase (TH) staining showing co-localization of adrenergic cells within the same ganglion; and (F) ChAT positivity of nerve adjacent to ganglion.
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Figure 4 Longitudinal (A) and transmural (B) autonomic nerve distribution. ChAT = anticholine acetyltransferase; LA = left atrium; TH = antityrosine hydroxylase.
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Figure 5 Circumferential distribution of autonomic nerves at the pulmonary vein (PV)-left atrium (LA) junction. AO = aorta; CS = coronary sinus; IVC = inferior vena cava; LA = left atrium; LI = left inferior pulmonary vein; LS = left superior pulmonary vein; PA = pulmonary artery; PV = pulmonary veins; RI = right inferior pulmonary vein; RS = right superior pulmonary vein; SVC = superior vena cava; VOM = vein of marshall.
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Figure 6 Co-location of adrenergic and cholinergic nerves at a tissue level (A1 to A5) and at a cellular level within nerve fiber trunks (B1 to B2, D1 to D3) and cardiac ganglia (C1 to C2, E1 to E3). See text for explanations. ChAT = anticholine acetyltransferase; TH = antityrosine hydroxylase.
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Figure 7 Adrenocholinergic neural connections within cardiac ganglia (A1 to A4), and ganglion cells expressing dual adrenergic and cholinergic phenotypes (B1 to B4). ChAT = anticholine acetyltransferase; TH = antityrosine hydroxylase.
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