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Original Article

Effect of Renal Denervation on Neurohumoral Activation Triggering Atrial Fibrillation in Obstructive Sleep Apnea

Dominik Linz, Mathias Hohl, Alexander Nickel, Felix Mahfoud, Michael Wagner, Sebastian Ewen, Ulrich Schotten, Christoph Maack, Klaus Wirth, Michael Böhm
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https://doi.org/10.1161/HYPERTENSIONAHA.113.01728
Hypertension. 2013;HYPERTENSIONAHA.113.01728
Originally published August 19, 2013
Dominik Linz
From the Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg, Saar, Germany (D.L., M.H., A.N., F.M., M.W., S.E., C.M., M.B.); Cardiovascular Research Institute Maastricht, The Netherlands (U.S.); and Sanofi-Aventis Deutschland GmbH, R&D, Aging/Disability of CVC origin, Frankfurt, Germany (K.W.).
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Mathias Hohl
From the Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg, Saar, Germany (D.L., M.H., A.N., F.M., M.W., S.E., C.M., M.B.); Cardiovascular Research Institute Maastricht, The Netherlands (U.S.); and Sanofi-Aventis Deutschland GmbH, R&D, Aging/Disability of CVC origin, Frankfurt, Germany (K.W.).
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Alexander Nickel
From the Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg, Saar, Germany (D.L., M.H., A.N., F.M., M.W., S.E., C.M., M.B.); Cardiovascular Research Institute Maastricht, The Netherlands (U.S.); and Sanofi-Aventis Deutschland GmbH, R&D, Aging/Disability of CVC origin, Frankfurt, Germany (K.W.).
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Felix Mahfoud
From the Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg, Saar, Germany (D.L., M.H., A.N., F.M., M.W., S.E., C.M., M.B.); Cardiovascular Research Institute Maastricht, The Netherlands (U.S.); and Sanofi-Aventis Deutschland GmbH, R&D, Aging/Disability of CVC origin, Frankfurt, Germany (K.W.).
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Michael Wagner
From the Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg, Saar, Germany (D.L., M.H., A.N., F.M., M.W., S.E., C.M., M.B.); Cardiovascular Research Institute Maastricht, The Netherlands (U.S.); and Sanofi-Aventis Deutschland GmbH, R&D, Aging/Disability of CVC origin, Frankfurt, Germany (K.W.).
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Sebastian Ewen
From the Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg, Saar, Germany (D.L., M.H., A.N., F.M., M.W., S.E., C.M., M.B.); Cardiovascular Research Institute Maastricht, The Netherlands (U.S.); and Sanofi-Aventis Deutschland GmbH, R&D, Aging/Disability of CVC origin, Frankfurt, Germany (K.W.).
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Ulrich Schotten
From the Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg, Saar, Germany (D.L., M.H., A.N., F.M., M.W., S.E., C.M., M.B.); Cardiovascular Research Institute Maastricht, The Netherlands (U.S.); and Sanofi-Aventis Deutschland GmbH, R&D, Aging/Disability of CVC origin, Frankfurt, Germany (K.W.).
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Christoph Maack
From the Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg, Saar, Germany (D.L., M.H., A.N., F.M., M.W., S.E., C.M., M.B.); Cardiovascular Research Institute Maastricht, The Netherlands (U.S.); and Sanofi-Aventis Deutschland GmbH, R&D, Aging/Disability of CVC origin, Frankfurt, Germany (K.W.).
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Klaus Wirth
From the Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg, Saar, Germany (D.L., M.H., A.N., F.M., M.W., S.E., C.M., M.B.); Cardiovascular Research Institute Maastricht, The Netherlands (U.S.); and Sanofi-Aventis Deutschland GmbH, R&D, Aging/Disability of CVC origin, Frankfurt, Germany (K.W.).
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Michael Böhm
From the Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg, Saar, Germany (D.L., M.H., A.N., F.M., M.W., S.E., C.M., M.B.); Cardiovascular Research Institute Maastricht, The Netherlands (U.S.); and Sanofi-Aventis Deutschland GmbH, R&D, Aging/Disability of CVC origin, Frankfurt, Germany (K.W.).
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Abstract

Obstructive sleep apnea is characterized by repetitive collapses of the upper airway, negative thoracic pressure periods, and intermittent hypoxia, stimulating the autonomic nervous system. The increased sympathetic drive during obstructive sleep apnea results in postapneic blood pressure rises and neurohumoral activation potentially involved in the initiation and progression to permanent atrial fibrillation (AF). In a pig model mimicking obstructive sleep apnea, we studied the effects of repetitive obstructive respiratory events for 4 hours on the occurrence of spontaneous AF episodes, postapneic blood pressure rises, and neurohumoral activation. In addition, renal sympathetic denervation was performed to investigate the impact of the sympathetic nervous system. Repetitive obstructive respiratory events caused pronounced postapneic blood pressure rises, prolonged duration of spontaneous AF episodes triggered by spontaneous atrial beats, and increased plasma renin activity and aldosterone concentrations. This was associated with increased nicotinamide adenine dinucleotide phosphate-oxidase activity, reduced antioxidative capacity, and elevated expression of connective tissue growth factor, a redox-sensitive mediator of fibrosis. Renal sympathetic denervation inhibited postapneic blood pressure rises and decreased plasma renin activity and aldosterone concentrations. The occurrence and duration of spontaneous AF were reduced comparable with a combined pharmacological blockade of angiotensin receptor and β-adrenoceptor. Increased atrial oxidative stress, together with the activation of profibrotic pathways and intermittent hypoxia, was not attenuated after renal sympathetic denervation. Repetitive obstructive respiratory events triggered spontaneous AF, increased atrial oxidative stress, and activated profibrotic pathways in the atrium. Renal sympathetic denervation reduced spontaneous AF and postapneic blood pressure rises by combined reduction of sympathetic drive and components of the circulating renin–angiotensin system. However, the generation of atrial oxidative stress was not modulated.

  • atrial fibrillation
  • autonomic nervous system
  • oxidative stress
  • sleep apnea, obstructive
  • Received May 17, 2013.
  • Revision received June 30, 2013.
  • Accepted July 27, 2013.
  • © 2013 American Heart Association, Inc.
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    Effect of Renal Denervation on Neurohumoral Activation Triggering Atrial Fibrillation in Obstructive Sleep Apnea
    Dominik Linz, Mathias Hohl, Alexander Nickel, Felix Mahfoud, Michael Wagner, Sebastian Ewen, Ulrich Schotten, Christoph Maack, Klaus Wirth and Michael Böhm
    Hypertension. 2013;HYPERTENSIONAHA.113.01728, originally published August 19, 2013
    https://doi.org/10.1161/HYPERTENSIONAHA.113.01728

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    Effect of Renal Denervation on Neurohumoral Activation Triggering Atrial Fibrillation in Obstructive Sleep Apnea
    Dominik Linz, Mathias Hohl, Alexander Nickel, Felix Mahfoud, Michael Wagner, Sebastian Ewen, Ulrich Schotten, Christoph Maack, Klaus Wirth and Michael Böhm
    Hypertension. 2013;HYPERTENSIONAHA.113.01728, originally published August 19, 2013
    https://doi.org/10.1161/HYPERTENSIONAHA.113.01728
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