Cardiac Sympathetic Modulation in Response to Apneas/Hypopneas through Heart Rate Variability Analysis

Autonomic dysfunction is recognized to contribute to cardiovascular consequences in obstructive sleep apnea/hypopnea syndrome (OSAHS) patients who present predominant cardiovascular sympathetic activity that persists during wakefulness. Here, we examined 1) the factors that influence sympathetic cardiac modulation in response to apneas/hypopneas; and 2) the influence of autonomic activity during apneas/hypopneas on CA. Sixteen OSAHS patients underwent in-hospital polysomnography. RR interval (RR) and RR spectral analysis using wavelet transform were used to study parasympathetic (high frequency power: HFWV) and sympathetic (low frequency power: LFWV and LFWV/HFWV ratio) activity before and after apnea/hypopnea termination. Autonomic cardiac modulations were compared according to sleep stage, apnea/hypopnea type and duration, arterial oxygen saturation, and presence of CA. At apnea/hypopnea termination, RR decreased (p<0.001) while LFWV (p = 0.001) and LFWV/HFWV ratio (p = 0.001) increased. Only RR and LFWV/HFWV ratio changes were higher when apneas/hypopneas produced CA (p = 0.030 and p = 0.035, respectively) or deep hypoxia (p = 0.023 and p = 0.046, respectively). Multivariate statistical analysis showed that elevated LFWV (p = 0.006) and LFWV/HFWV ratio (p = 0.029) during apneas/hypopneas were independently related to higher CA occurrence. Both the arousal and hypoxia processes may contribute to sympathetic cardiovascular overactivity by recurrent cardiac sympathetic modulation in response to apneas/hypopneas. Sympathetic overactivity also may play an important role in the acute central response to apneas/hypopneas, and in the sleep fragmentation.

[1]  V. Somers,et al.  Chemoreflexes--physiology and clinical implications. , 2003, Acta physiologica Scandinavica.

[2]  J. Weil,et al.  Bradycardia during sleep apnea. Characteristics and mechanism. , 1982, The Journal of clinical investigation.

[3]  F. Abboud,et al.  Interaction of baroreceptor and chemoreceptor reflex control of sympathetic nerve activity in normal humans. , 1991, The Journal of clinical investigation.

[4]  E. Sforza,et al.  Heart rate increment in the diagnosis of obstructive sleep apnoea in an older population. , 2012, Sleep medicine.

[5]  Jose M Marin,et al.  Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study , 2005, The Lancet.

[6]  M. Bonnet,et al.  Heart rate variability: sleep stage, time of night, and arousal influences. , 1997, Electroencephalography and clinical neurophysiology.

[7]  M. Malik Heart Rate Variability , 1996, Clinical cardiology.

[8]  M Chiodi,et al.  Different heart rate patterns in obstructive apneas during NREM sleep. , 1997, Sleep.

[9]  M. Merri,et al.  Sampling frequency of the electrocardiogram for spectral analysis of the heart rate variability , 1988, IEEE Transactions on Biomedical Engineering.

[10]  R. Cole,et al.  Postural baroreflex stimuli may affect EEG arousal and sleep in humans. , 1989, Journal of applied physiology.

[11]  A. Chesson,et al.  The American Academy of Sleep Medicine (AASM) Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications , 2007 .

[12]  F. Chouchoul,et al.  Autonomic pain responses during sleep: A study of heart rate variability , 2011 .

[13]  Vincent Ibanez,et al.  Cardiac activation during arousal in humans: further evidence for hierarchy in the arousal response , 2000, Clinical Neurophysiology.

[14]  N. Montano,et al.  Contribution of tonic chemoreflex activation to sympathetic activity and blood pressure in patients with obstructive sleep apnea. , 1998, Circulation.

[15]  S. Launois,et al.  Drug-induced arterial pressure elevation is associated with arousal from NREM sleep in normal volunteers. , 1999, Journal of applied physiology.

[16]  J. Floras,et al.  Obstructive sleep apnoea and its cardiovascular consequences , 2009, The Lancet.

[17]  A. Guggisberg,et al.  The significance of the sympathetic nervous system in the pathophysiology of periodic leg movements in sleep. , 2007, Sleep.

[18]  J. Mercer,et al.  Acute cardiovascular responses to arousal from non-REM sleep during normoxia and hypoxia. , 2001, Sleep.

[19]  E. Sforza,et al.  Time-dependent variation in cerebral and autonomic activity during periodic leg movements in sleep: implications for arousal mechanisms , 2002, Clinical Neurophysiology.

[20]  S. Esnaola,et al.  Obstructive sleep apnea-hypopnea and related clinical features in a population-based sample of subjects aged 30 to 70 yr. , 2001, American journal of respiratory and critical care medicine.

[21]  Anna Blasi,et al.  Cardiovascular variability after arousal from sleep: time-varying spectral analysis. , 2003, Journal of applied physiology.

[22]  P. Berger,et al.  Effect of sinoaortic denervation on arousal responses to hypotension in newborn lambs. , 1989, The American journal of physiology.

[23]  G. Breithardt,et al.  Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. , 1996 .

[24]  R. Kronenberg,et al.  Ventilatory and heart rate responses to hypoxia and hypercapnia during sleep in adults. , 1982, Journal of applied physiology: respiratory, environmental and exercise physiology.

[25]  T. Young,et al.  Sleep fragmentation, awake blood pressure, and sleep-disordered breathing in a population-based study. , 2000, American journal of respiratory and critical care medicine.

[26]  A. Malliani,et al.  Heart rate variability. Standards of measurement, physiological interpretation, and clinical use , 1996 .

[27]  N. Douglas,et al.  Spectral oscillations of RR intervals in sleep apnoea/hypopnoea syndrome patients , 2003, European Respiratory Journal.

[28]  F. Abboud,et al.  Chemoreflexes--responses, interactions and implications for sleep apnea. , 1993, Sleep.

[29]  J. Pépin,et al.  Obstructive sleep apnoea and the autonomic nervous system. , 1998, Sleep medicine reviews.

[30]  G. Lavigne,et al.  Sleep bruxism is associated to micro‐arousals and an increase in cardiac sympathetic activity , 2006, Journal of sleep research.

[31]  D. White,et al.  The cardiorespiratory activation response at an arousal from sleep is independent of the level of CO2 , 2006, Journal of sleep research.

[32]  Luciano Bernardi,et al.  Autonomic modulation of heart rate during obstructive versus central apneas in patients with sleep-disordered breathing. , 2003, American journal of respiratory and critical care medicine.

[33]  Christian Guilleminault,et al.  Heart rate variability, sympathetic and vagal balance and EEG arousals in upper airway resistance and mild obstructive sleep apnea syndromes. , 2005, Sleep medicine.

[34]  D L Eckberg,et al.  Mechanisms underlying very-low-frequency RR-interval oscillations in humans. , 1998, Circulation.

[35]  H. Schulz,et al.  Phasic or transient? Comment on the terminology of the AASM manual for the scoring of sleep and associated events. , 2007, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[36]  I Fietze,et al.  Arousability in sleep apnoea/hypopnoea syndrome patients , 2002, European Respiratory Journal.

[37]  J. Pépin,et al.  At 68 years, unrecognised sleep apnoea is associated with elevated ambulatory blood pressure , 2012, European Respiratory Journal.

[38]  J. Barthélémy,et al.  Sympathetic overactivity due to sleep fragmentation is associated with elevated diurnal systolic blood pressure in healthy elderly subjects: the PROOF-SYNAPSE study. , 2013, European heart journal.

[39]  V Pichot,et al.  Autonomic pain responses during sleep : a study of heart rate variability , 2010 .

[40]  B. Wuyam,et al.  Abnormal autonomic stress responses in obstructive sleep apnoea are reversed by nasal continuous positive airway pressure. , 1996, European Respiratory Journal.