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Heart Failure Decreases Nerve Activity in the Right Atrial Ganglionated Plexus

Authors

  • TETSUJI SHINOHARA M.D., Ph.D.,

    1. Division of Cardiology, Department of Medicine, Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana, USA
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  • MARK J. SHEN M.D.,

    1. Division of Cardiology, Department of Medicine, Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana, USA
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  • SEONGWOOK HAN M.D., Ph.D.,

    1. Division of Cardiology, Department of Medicine, Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana, USA
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  • MITSUNORI MARUYAMA M.D., Ph.D.,

    1. Division of Cardiology, Department of Medicine, Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana, USA
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  • HYUNG-WOOK PARK M.D., Ph.D.,

    1. Division of Cardiology, Department of Medicine, Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana, USA
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  • MICHAEL C. FISHBEIN M.D.,

    1. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California, USA
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  • CHANGYU SHEN Ph.D.,

    1. Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana, USA
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  • PENG-SHENG CHEN M.D.,

    1. Division of Cardiology, Department of Medicine, Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana, USA
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  • SHIEN-FONG LIN Ph.D.

    1. Division of Cardiology, Department of Medicine, Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana, USA
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  • Supported in part by National Institutes of Health grants P01 HL78931, R01 HL78932, 71140, R21 HL106554; a Heart Rhythm Society Fellowship in Cardiac Pacing and Electrophysiology (M.J.S.); a Nihon Kohden/St. Jude Medical Electrophysiology fellowship (M. M.); Medtronic-Zipes Endowments (P.-S.C.); and an American Heart Association Established Investigator Award (S.-F.L.).

  • Dr. Chen reports receiving support in the form of research equipment from St. Jude Medical, Medtronic, Cyberonics, and CryoCath. Other authors: No disclosures.

Address for correspondence: Shien-Fong Lin, Ph.D., 1800 N. Capitol Ave., 308 E, Indianapolis, IN 46202, USA. Fax: 317-962-0100; E-mail: linsf@iupui.edu

Abstract

Reduced Vagal Control in Heart Failure.

Objective: We tested the hypothesis that heart failure (HF) results in right atrial ganglionated plexus (RAGP) denervation that contributes to sinoatrial node dysfunction.

Background: HF is associated with sinoatrial node dysfunction. However, the detailed mechanisms remain unclear.

Methods: We recorded nerve activity (NA) from the RAGP, right stellate ganglion (SG), and right vagal nerve in 7 ambulatory dogs at baseline and after pacing-induced HF. We also determined the effects of RAGP stimulation in isolated normal and HF canine RA.

Results: NAs in both the SG and vagal were significantly higher in HF than at baseline. The relationship between 1-minute integrated NAs of vagal and RAGP showed either a positive linear correlation (Group 1, n = 4) or an L-shaped correlation (Group 2, n = 3). In all dogs, a reduced heart rate was observed when vagal-NA was associated with simultaneously increased RAGP-NA. On the other hand, when vagal-NA was not associated with increased RAGP-NA, the heart rate was not reduced. The induction of HF significantly decreased RAGP-NA in all dogs (P < 0.05). Stimulating the superior RAGP in isolated RA significantly reduced the sinus rate in normal but not the HF hearts. Immunohistochemical staining revealed lower densities of tyrosine hydroxylase- and choline acetyltransferase-positive nerve tissues in HF RAGP than normal (P < 0.001 and P = 0.001, respectively).

Conclusions: The RAGP-NA is essential for the vagal nerve to counterbalance the SG in sinus rate control. In HF, RAGP denervation and decreased RAGP-NA contribute to the sinus node dysfunction.

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