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, Hongmei Li, Sebastian Wachsmann-Hogiu, Lan Chen, Peng-Sheng Chen, Michael C. Fishbein

Research output: Contribution to journalArticle

225 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)132-143
Number of pages12
JournalJournal of the American College of Cardiology
Volume48
Issue number1
DOIs
StatePublished - Jul 4 2006
Externally publishedYes

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Catheter Ablation
Pulmonary Veins
Heart Atria
Autonomic Pathways
Muscles
Choline O-Acetyltransferase
Tyrosine 3-Monooxygenase
Adrenergic Agents
Atrial Fibrillation
Cholinergic Agents
Veins
Staining and Labeling
Antibodies

ASJC Scopus subject areas

  • Nursing(all)

Cite this

Autonomic Innervation and Segmental Muscular Disconnections at the Human Pulmonary Vein-Atrial Junction. Implications for Catheter Ablation of Atrial-Pulmonary Vein Junction. / Tan, Alex Y.; Li, Hongmei; Wachsmann-Hogiu, Sebastian; Chen, Lan; Chen, Peng-Sheng; Fishbein, Michael C.

In: Journal of the American College of Cardiology, Vol. 48, No. 1, 04.07.2006, p. 132-143.

Research output: Contribution to journalArticle

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abstract = "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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T1 - Autonomic Innervation and Segmental Muscular Disconnections at the Human Pulmonary Vein-Atrial Junction. Implications for Catheter Ablation of Atrial-Pulmonary Vein Junction

AU - Tan, Alex Y.

AU - Li, Hongmei

AU - Wachsmann-Hogiu, Sebastian

AU - Chen, Lan

AU - Chen, Peng-Sheng

AU - Fishbein, Michael C.

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N2 - 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.

AB - 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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