title: Resonance as the Mechanism of Daytime Periodic Breathing in Patients with Heart Failure.
abstract: In patients with chronic heart failure, daytime oscillatory breathing at rest is associated with a high risk of mortality. Experimental evidence, including exaggerated ventilatory responses to CO2and prolonged circulation time, implicates the ventilatory control system and suggests feedback instability (loop gain > 1) is responsible. However, daytime oscillatory patterns often appear remarkably irregular versus classic instability (Cheyne-Stokes respiration), suggesting our mechanistic understanding is limited.
  
  
  
  We propose that daytime ventilatory oscillations generally result from a chemoreflex resonance, in which spontaneous biological variations in ventilatory drive repeatedly induce temporary and irregular ringing effects. Importantly, the ease with which spontaneous biological variations induce irregular oscillations (resonance "strength") rises profoundly as loop gain rises toward 1. We tested this hypothesis through a comparison of mathematical predictions against actual measurements in patients with heart failure and healthy control subjects.
  
  
  
  In 25 patients with chronic heart failure and 25 control subjects, we examined spontaneous oscillations in ventilation and separately quantified loop gain using dynamic inspired CO2stimulation.
  
  
  
  Resonance was detected in 24 of 25 patients with heart failure and 18 of 25 control subjects. With increased loop gain-consequent to increased chemosensitivity and delay-the strength of spontaneous oscillations increased precipitously as predicted (r = 0.88), yielding larger (r = 0.78) and more regular (interpeak interval SD, r = -0.68) oscillations (P < 0.001 for all, both groups combined).
  
  
  
  Our study elucidates the mechanism underlying daytime ventilatory oscillations in heart failure and provides a means to measure and interpret these oscillations to reveal the underlying chemoreflex hypersensitivity and reduced stability that foretells mortality in this population.
authors: 1 Division of Sleep and Circadian Disorders and.|2 Department of Allergy, Immunology and Respiratory Medicine and Central Clinical School, The Alfred and Monash University, Melbourne, Victoria, Australia.
authors: Scott A
authors: SA
authors: Sands
authors: 3 International Center for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, United Kingdom.|4 Department of Clinical Engineering, Royal Brompton Hospital, London, United Kingdom.
authors: Yoseph
authors: Y
authors: Mebrate
authors: 1 Division of Sleep and Circadian Disorders and.|5 Sleep and Circadian Medicine Laboratory, Department of Physiology, and.|6 School of Psychological Sciences and Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Melbourne, Victoria, Australia.
authors: Bradley A
authors: BA
authors: Edwards
authors: 1 Division of Sleep and Circadian Disorders and.
authors: Shamim
authors: S
authors: Nemati
authors: 7 Institute of Cardiovascular Sciences, University College London, London, United Kingdom; and.
authors: Charlotte H
authors: CH
authors: Manisty
authors: 8 Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors: Akshay S
authors: AS
authors: Desai
authors: 1 Division of Sleep and Circadian Disorders and.
authors: Andrew
authors: A
authors: Wellman
authors: 3 International Center for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors: Keith
authors: K
authors: Willson
authors: 3 International Center for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors: Darrel P
authors: DP
authors: Francis
authors: 1 Division of Sleep and Circadian Disorders and.
authors: James P
authors: JP
authors: Butler
authors: 1 Division of Sleep and Circadian Disorders and.|9 Division of Pulmonary and Critical Care Medicine, University of California San Diego, La Jolla, California.
authors: Atul
authors: A
authors: Malhotra
mesh_terms: D002245:Carbon Dioxide / Q000378:metabolism; D016022:Case-Control Studies; D002639:Cheyne-Stokes Respiration / Q000209:etiology / Q000503:physiopathology; D002940:Circadian Rhythm / Q000502:physiology*; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D056152:Respiratory Rate / Q000502:physiology*
chemical_list: D002245:Carbon Dioxide
keywords: Cheyne-Stokes respiration; chemosensitivity; heart failure; instability; loop gain