Determinants of heart rate variability in obstructive sleep apnea syndrome during wakefulness and sleep.

Heart rate variability (HRV) is mediated by at least three primary mechanisms: 1) vagal feedback from pulmonary stretch receptors (PSR), 2) central medullary coupling between respiratory and cardiovagal neurons (RCC), and 3) arterial baroreflex (ABR)-induced fluctuations. We employed a noninvasive experimental protocol in conjunction with a minimal model to determine how these sources of HRV are altered in obstructive sleep apnea syndrome (OSAS). Respiration, heart rate, and blood pressure were monitored in eight normal subjects and nine untreated OSAS patients in relaxed wakefulness and stage 2 and rapid eye movement sleep. A computer-controlled ventilator delivered inspiratory pressures that varied randomly from breath to breath. Application of the model to the corresponding subject responses allowed the delineation of the three components of HRV. In all states, RCC gain was lower in OSAS patients than in normal subjects (P < 0.04). ABR gain was also reduced in OSAS patients (P < 0.03). RCC and ABR gains increased from wakefulness to sleep (P < 0.04). However, there was no difference in PSR gain between subject groups or across states. The findings of this study suggest that the adverse autonomic effects of OSAS include impairment of baroreflex gain and central respiratory-cardiovascular coupling, but the component of respiratory sinus arrhythmia that is mediated by lung vagal feedback remains intact.

[1]  J. Rissanen.  Estimation of structure by minimum description length , 1982 .

[2]  A. Rechtschaffen.  A manual of standardized terminology, techniques and scoring system for sleep of human subjects , 1968 .

[3]  Arthur S Slutsky,et al.  Respiratory sinus arrhythmia in dogs. Effects of phasic afferents and chemostimulation. , 1991, The Journal of clinical investigation.

[4]  H. Nagaraja,et al.  Heart rate variability: origins, methods, and interpretive caveats. , 1997, Psychophysiology.

[5]  T. DebRoy,et al.  Modeling of the role of atomic hydrogen in heat transfer during hot filament assisted deposition of diamond , 1992 .

[6]  A. Baydur.  Decay of inspiratory muscle pressure during expiration in anesthetized kyphoscoliosis patients. , 1992, Journal of applied physiology.

[7]  J. Dempsey,et al.  Role of respiratory motor output in within-breath modulation of muscle sympathetic nerve activity in humans. , 1999, Circulation research.

[8]  Heart rate variability in patients with obstructive sleep apnea. , 1996, Clinical science.

[9]  F. Abboud,et al.  Sympathetic neural mechanisms in obstructive sleep apnea. , 1995, The Journal of clinical investigation.

[10]  C W Whitney,et al.  Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. , 2001, American journal of respiratory and critical care medicine.

[11]  R. Berry,et al.  Spectral indices of cardiac autonomic function in obstructive sleep apnea. , 1999, Sleep.

[12]  W A Zin,et al.  Respiratory mechanics during halothane anesthesia and anesthesia-paralysis in humans. , 1983, Journal of applied physiology: respiratory, environmental and exercise physiology.

[13]  F. Yasuma,et al.  Respiratory sinus arrhythmia: why does the heartbeat synchronize with respiratory rhythm? , 2004, Chest.

[14]  David Watts.  Apnea , 1997, The Lancet.

[15]  E. Wolpert.  A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. , 1969 .

[16]  K. Yana,et al.  A time domain approach for the fluctuation analysis of heart rate related to instantaneous lung volume , 1993, IEEE Transactions on Biomedical Engineering.

[17]  A. Blasi,et al.  Model-based assessment of autonomic control in obstructive sleep apnea syndrome during sleep. , 2003, American journal of respiratory and critical care medicine.

[18]  Michael C. K. Khoo,et al.  Physiological Control Systems: Analysis, Simulation, and Estimation , 1999 .

[19]  M. Khoo,et al.  Estimation of cardiorespiratory transfer under spontaneous breathing conditions: a theoretical study. , 1997, The American journal of physiology.

[20]  Allan I. Pack,et al.  Regulation of breathing , 1994 .

[21]  J S Floras,et al.  Continuous positive airway pressure increases heart rate variability in congestive heart failure. , 1995, Journal of the American College of Cardiology.

[22]  C. D'Ambrosio,et al.  Sleep-related breathing disorders and cardiovascular disease. , 2000, The American journal of medicine.

[23]  R J Cohen,et al.  System identification of closed-loop cardiovascular control: effects of posture and autonomic blockade. , 1997, The American journal of physiology.

[24]  G. Anrep,et al.  Respiratory Variations of the Heart Rate. II.--The Central Mechanism of the Respiratory Arrhythmia and the Inter-Relations between the Central and the Reflex Mechanisms , 1936 .

[25]  M. Uusitupa,et al.  Cardiac sympathovagal balance during sleep apnea episodes. , 1996, Clinical physiology.

[26]  U. Wiklund,et al.  Autonomic cardiovascular regulation in patients with obstructive sleep apnoea: a study based on spectral analysis of heart rate variability. , 2000, Clinical physiology.

[27]  P G Katona,et al.  Cardiac vagal efferent activity and heart period in the carotid sinus reflex. , 1970, The American journal of physiology.

[28]  K. Chon,et al.  A dual-input nonlinear system analysis of autonomic modulation of heart rate , 1996, IEEE Transactions on Biomedical Engineering.

[29]  E. d’Angelo,et al.  Statics of the respiratory system , 1999 .

[30]  Michael C. K. Khoo,et al.  Physiological Control Systems , 2018 .

[31]  N. Simionescu,et al.  The Cardiovascular System , 1983 .

[32]  J A Dempsey,et al.  Respiratory sinus arrhythmia in humans: an obligatory role for vagal feedback from the lungs. , 1995, Journal of applied physiology.

[33]  R. Cohen,et al.  An Efficient Algorithm for Spectral Analysis of Heart Rate Variability , 1986, IEEE Transactions on Biomedical Engineering.

[34]  J. T. Shepherd,et al.  Peripheral circulation and organ blood flow , 1983 .

[35]  D. L. Eckberg.  Respiratory sinus arrhythmia and other human cardiovascular neural periodicities , 1995 .

[36]  M. Younes,et al.  Control of breathing during sleep assessed by proportional assist ventilation. , 1998, Journal of applied physiology.

[37]  N. Montano,et al.  Altered cardiovascular variability in obstructive sleep apnea. , 1998, Circulation.

[38]  P. Ponikowski,et al.  Chemoreceptor-Baroreceptor Interactions in Cardiovascular Disease , 2000 .

[39]  C. Zwillich,et al.  Sleep apnoea and autonomic function. , 1998, Thorax.

[40]  EW Russi,et al.  Diving and the risk of barotrauma , 1998, Thorax.

[41]  G. Anrep,et al.  Respiratory Variations of the Heart Rate. I.--The Reflex Mechanism of the Respiratory Arrhythmia , 1936 .

[42]  E. Bruce,et al.  Override of spontaneous respiratory pattern generator reduces cardiovascular parasympathetic influence. , 1995, Journal of applied physiology.

[43]  E. Phillipson,et al.  Obstructive sleep apnea as a cause of systemic hypertension. Evidence from a canine model. , 1997, The Journal of clinical investigation.

[44]  R. Berry,et al.  Model-based assessment of autonomic control in obstructive sleep apnea syndrome. , 2003, Sleep.

[45]  T. D. Bradley,et al.  Haemodynamic effects of continuous positive airway pressure in humans with normal and impaired left ventricular function. , 1995, Clinical science.

[46]  I Korhonen,et al.  Assessment of arterial and cardiopulmonary baroreflex gains from simultaneous recordings of spontaneous cardiovascular and respiratory variability. , 2001, Journal of hypertension.

[47]  A. Malliani,et al.  Cardiovascular variability signals: towards the identification of a closed-loop model of the neural control mechanisms , 1988, IEEE Transactions on Biomedical Engineering.

[48]  A J Camm,et al.  Prognostic value of baroreflex sensitivity testing after acute myocardial infarction. , 1992, British heart journal.

[49]  J. Floras,et al.  Sleep apnea : implications in cardiovascular and cerebrovascular disease , 2000 .

[50]  M. Piepoli,et al.  Origin of respiratory sinus arrhythmia in conscious humans. An important role for arterial carotid baroreceptors. , 1997, Circulation.