Nerve sprouting and sympathetic hyperinnervation in a canine model of atrial fibrillation produced by prolonged right atrial pacing

Che Ming Chang, Tsu Juey Wu, Shengmei Zhou, Rahul N. Doshi, Moon Hyoung Lee, Toshihiko Ohara, Michael C. Fishbein, Hrayr S. Karagueuzian, Peng-Sheng Chen, Lan Chen

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

Background - Long-term rapid atrial pacing may result in atrial fibrillation (AF) in dogs. Whether there is histological evidence for neural remodeling is unclear. Method and Results - We performed rapid right atrial pacing in 6 dogs for 111±76 days to induce sustained AF. Tissues from 6 healthy dogs were used as controls. Immunocytochemical staining of cardiac nerves was performed using anti-growth-associated protein 43 (GAP43) and anti-tyrosine hydroxylase (TH) antibodies. In dogs with AF, the density of GAP43-positive and TH-positive nerves in the right atrium was 470±406 and 231±126 per mm2, respectively, which was significantly (P2, respectively). The density of GAP43-positive and TH-positive nerves in the atrial septum was 317±36 and 155±85 per mm2, respectively, and was significantly (P2, respectively). Similarly, the density of GAP43-positive and TH-positive nerves in the left atrium of dogs with AF was 119±61 and 91±40 per mm2, respectively, which was significantly (P2, respectively). Furthermore, in dogs with AF, the right atrium had a significantly higher nerve density than the left atrium. Microscopic examinations revealed an inhomogeneous distribution of cardiac nerves within each sampling site. Conclusions - Significant nerve sprouting and sympathetic hyperinnervation are present in a canine model of sustained AF produced by prolonged right atrial pacing. The magnitude of nerve sprouting and hyperinnervation was higher in the right atrium than in the left atrium.

Original languageEnglish (US)
Pages (from-to)22-25
Number of pages4
JournalCirculation
Volume103
Issue number1
StatePublished - Jan 9 2001
Externally publishedYes

Fingerprint

Heart Atria
Atrial Fibrillation
GAP-43 Protein
Canidae
Tyrosine 3-Monooxygenase
Dogs
Atrial Septum
Staining and Labeling
Antibodies

Keywords

  • Catecholamines
  • Electrophysiology
  • Nervous system, autonomic
  • Remodeling
  • Tachyarrhythmias

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Nerve sprouting and sympathetic hyperinnervation in a canine model of atrial fibrillation produced by prolonged right atrial pacing. / Chang, Che Ming; Wu, Tsu Juey; Zhou, Shengmei; Doshi, Rahul N.; Lee, Moon Hyoung; Ohara, Toshihiko; Fishbein, Michael C.; Karagueuzian, Hrayr S.; Chen, Peng-Sheng; Chen, Lan.

In: Circulation, Vol. 103, No. 1, 09.01.2001, p. 22-25.

Research output: Contribution to journalArticle

Chang, CM, Wu, TJ, Zhou, S, Doshi, RN, Lee, MH, Ohara, T, Fishbein, MC, Karagueuzian, HS, Chen, P-S & Chen, L 2001, 'Nerve sprouting and sympathetic hyperinnervation in a canine model of atrial fibrillation produced by prolonged right atrial pacing', Circulation, vol. 103, no. 1, pp. 22-25.
Chang, Che Ming ; Wu, Tsu Juey ; Zhou, Shengmei ; Doshi, Rahul N. ; Lee, Moon Hyoung ; Ohara, Toshihiko ; Fishbein, Michael C. ; Karagueuzian, Hrayr S. ; Chen, Peng-Sheng ; Chen, Lan. / Nerve sprouting and sympathetic hyperinnervation in a canine model of atrial fibrillation produced by prolonged right atrial pacing. In: Circulation. 2001 ; Vol. 103, No. 1. pp. 22-25.
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AU - Chang, Che Ming

AU - Wu, Tsu Juey

AU - Zhou, Shengmei

AU - Doshi, Rahul N.

AU - Lee, Moon Hyoung

AU - Ohara, Toshihiko

AU - Fishbein, Michael C.

AU - Karagueuzian, Hrayr S.

AU - Chen, Peng-Sheng

AU - Chen, Lan

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Y1 - 2001/1/9

N2 - Background - Long-term rapid atrial pacing may result in atrial fibrillation (AF) in dogs. Whether there is histological evidence for neural remodeling is unclear. Method and Results - We performed rapid right atrial pacing in 6 dogs for 111±76 days to induce sustained AF. Tissues from 6 healthy dogs were used as controls. Immunocytochemical staining of cardiac nerves was performed using anti-growth-associated protein 43 (GAP43) and anti-tyrosine hydroxylase (TH) antibodies. In dogs with AF, the density of GAP43-positive and TH-positive nerves in the right atrium was 470±406 and 231±126 per mm2, respectively, which was significantly (P2, respectively). The density of GAP43-positive and TH-positive nerves in the atrial septum was 317±36 and 155±85 per mm2, respectively, and was significantly (P2, respectively). Similarly, the density of GAP43-positive and TH-positive nerves in the left atrium of dogs with AF was 119±61 and 91±40 per mm2, respectively, which was significantly (P2, respectively). Furthermore, in dogs with AF, the right atrium had a significantly higher nerve density than the left atrium. Microscopic examinations revealed an inhomogeneous distribution of cardiac nerves within each sampling site. Conclusions - Significant nerve sprouting and sympathetic hyperinnervation are present in a canine model of sustained AF produced by prolonged right atrial pacing. The magnitude of nerve sprouting and hyperinnervation was higher in the right atrium than in the left atrium.

AB - Background - Long-term rapid atrial pacing may result in atrial fibrillation (AF) in dogs. Whether there is histological evidence for neural remodeling is unclear. Method and Results - We performed rapid right atrial pacing in 6 dogs for 111±76 days to induce sustained AF. Tissues from 6 healthy dogs were used as controls. Immunocytochemical staining of cardiac nerves was performed using anti-growth-associated protein 43 (GAP43) and anti-tyrosine hydroxylase (TH) antibodies. In dogs with AF, the density of GAP43-positive and TH-positive nerves in the right atrium was 470±406 and 231±126 per mm2, respectively, which was significantly (P2, respectively). The density of GAP43-positive and TH-positive nerves in the atrial septum was 317±36 and 155±85 per mm2, respectively, and was significantly (P2, respectively). Similarly, the density of GAP43-positive and TH-positive nerves in the left atrium of dogs with AF was 119±61 and 91±40 per mm2, respectively, which was significantly (P2, respectively). Furthermore, in dogs with AF, the right atrium had a significantly higher nerve density than the left atrium. Microscopic examinations revealed an inhomogeneous distribution of cardiac nerves within each sampling site. Conclusions - Significant nerve sprouting and sympathetic hyperinnervation are present in a canine model of sustained AF produced by prolonged right atrial pacing. The magnitude of nerve sprouting and hyperinnervation was higher in the right atrium than in the left atrium.

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