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(Circulation. 2001;103:22.)
© 2001 American Heart Association, Inc.
Brief Rapid Communications |
Nerve Sprouting and Sympathetic Hyperinnervation in a Canine Model of Atrial Fibrillation Produced by Prolonged Right Atrial Pacing
From the Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, Calif (C.-M.C., S.-M.Z., R.N.D, M.-H.L., T.O., H.S.K., P.-S.C.); Taichung Veterans General Hospital and National Yang-Ming University School of Medicine, Taiwan (T.-J.W.); the Department of Pathology and Laboratory Medicine at University of California at Los Angeles School of Medicine (M.C.F); and Children’s Hospital Los Angeles and University of Southern California Keck School of Medicine (L.S.C.), Los Angeles, Calif.
Correspondence to Lan S. Chen, MD, Division of Neurology #82, Children’s Hospital of Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027.
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 (P<0.001) higher than the nerve density in control tissues (25±32 and 88±40 per mm2, 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 (P<0.001) higher than the nerve density in control tissues (9±13 and 30±7 per mm2, 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 (P<0.001) higher than the nerve density in control tissues (10±15 and 38±39 per mm2, 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.
Key Words: remodeling • electrophysiology • nervous system, autonomic • tachyarrhythmias • catecholamines
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