Adjustment of the human respiratory system to increased upper airway resistance during sleep

A cardiorespiratory model incorporating control of the human upper airway during sleep is described. Most previous models have not considered the possibility that the upper airway could be a limiting factor for gas exchange. Our model was developed to also predict certain pathophysiological phenomena in the cardiorespiratory system that characterize heavy snoring or sleep apnea. We started by adapting our collapsible upper airway model to include the impact of nasal passage and larynx, and extended the model with equations for gas exchange in the lungs. A feedback loop both to the respiratory pump and the upper airway dilator muscles was included. The model enabled successful breath-by-breath simulations of obstructive events of the upper airway. Although the model incorporates several physiologically relevant components of the system, the simulation results suggest that only few parameters suffice to predict the key adjustments that the cardiorespiratory system is known to make in patients with heavy snoring.

[1]  J. Dempsey,et al.  Effect of hypercapnia on total pulmonary resistance during wakefulness and during NREM sleep. , 1991, The American review of respiratory disease.

[2]  J. Costantino,et al.  Accuracy of end-tidal and transcutaneous PCO2 monitoring during sleep. , 1994, Chest.

[3]  E. Bruce,et al.  Stability analysis of CO2 control of ventilation. , 1990, Journal of applied physiology.

[4]  S. McNamara,et al.  Respiratory challenge induces high frequency spiking on the static charge sensitive bed (SCSB). , 1996, The European respiratory journal.

[5]  Yoshitsugu Yamada,et al.  Analysis of the mechanisms of expiratory asynchrony in pressure support ventilation: a mathematical approach. , 2000, Journal of applied physiology.

[6]  W. Mapleson,et al.  A model lung with direct representation of respiratory muscle activity. , 1992, British journal of anaesthesia.

[7]  L. Huang,et al.  Neuromechanical interaction in human snoring and upper airway obstruction. , 1999, Journal of applied physiology.

[8]  H. T. Tran,et al.  Stability of the human respiratory control system II. Analysis of a three-dimensional delay state-space model , 2000, Journal of mathematical biology.

[9]  B Vielle,et al.  Delay equation analysis of human respiratory stability. , 1998, Mathematical biosciences.

[10]  L. Findley,et al.  Habitually sleepy drivers have a high frequency of automobile crashes associated with respiratory disorders during sleep. , 2000, American journal of respiratory and critical care medicine.

[11]  R. Berry,et al.  Within-night variation in respiratory effort preceding apnea termination and EEG delta power in sleep apnea. , 1998, Journal of applied physiology.

[12]  S. Pennycook,et al.  Synthesis of spherical luminescent particulate coatings , 1999 .

[13]  R. Berry,et al.  Ventilatory dynamics during transient arousal from NREM sleep: implications for respiratory control stability. , 1996, Journal of applied physiology.

[14]  W. Mapleson,et al.  Ventilatory assistance and respiratory muscle activity. 2: Simulation with an adaptive active ("aa" or "a-squared") model lung. , 1998, British journal of anaesthesia.

[15]  F. Sériès,et al.  Effects of inspiratory and expiratory positive pressure difference on airflow dynamics during sleep. , 1998, Journal of applied physiology.

[16]  N Gavriely,et al.  Theory and measurements of snores. , 1993, Journal of applied physiology.

[17]  T J Pedley,et al.  Prediction of coronary blood flow with a numerical model based on collapsible tube dynamics. , 1990, The American journal of physiology.

[18]  J Eugenín Generation of the respiratory rhythm: modelling the inspiratory off switch as a neural integrator. , 1995, Journal of theoretical biology.

[19]  Mats Gyllenberg,et al.  Detection of high-frequency respiratory movements during sleep , 2000, Comput. Methods Programs Biomed..

[20]  J. Alihanka,et al.  A new method for long-term monitoring of the ballistocardiogram, heart rate, and respiration. , 1981, The American journal of physiology.

[21]  G. Taylor Theory of operation of the quantum‐well injection laser without k selection , 1991 .

[22]  G. Kalamangalam,et al.  The role of the central chemoreceptor in causing periodic breathing. , 2000, IMA journal of mathematics applied in medicine and biology.

[23]  I. Riech,et al.  GROWTH AND OPTICAL CHARACTERIZATION OF INDIRECT-GAP ALXGA1-XAS ALLOYS , 1999 .

[24]  A I Pack,et al.  Sleep-induced periodic breathing and apnea: a theoretical study. , 1991, Journal of applied physiology.

[25]  H. Lorino,et al.  Effects of nasal prongs on nasal airflow resistance. , 2000, Chest.

[26]  J. Bates,et al.  Estimating respiratory mechanics in the presence of flow limitation. , 1999, Journal of applied physiology.

[27]  H. Lorino,et al.  Heavy snoring with upper airway resistance syndrome may induce intrinsic positive end-expiratory pressure. , 1998, Journal of applied physiology.

[28]  R D Kamm,et al.  Tube law for the intrapulmonary airway. , 1988, Journal of applied physiology.

[29]  D. White,et al.  Sleep and the ventilatory response to resistive loading in normal men. , 1988, Journal of applied physiology.

[30]  Mats Gyllenberg,et al.  Testing for Periodicity in Signals:an Application to Detect Partial Upper Airway Obstruction during Sleep , 2000 .

[31]  M Noshiro,et al.  Nonlinear identification of the PCO2 control system in man. , 1993, Computer methods and programs in biomedicine.

[32]  J. Dempsey,et al.  Effect of mechanical loading on expiratory and inspiratory muscle activity during NREM sleep. , 1990, Journal of applied physiology.

[33]  M. Fatemian,et al.  Identification of fast and slow ventilatory responses to carbon dioxide under hypoxic and hyperoxic conditions in humans , 1999, The Journal of physiology.

[34]  S A Shea,et al.  The effect of sleep on reflex genioglossus muscle activation by stimuli of negative airway pressure in humans. , 1994, The Journal of physiology.

[35]  A. J. Bart,et al.  Mathematical analysis and digital simulation of the respiratory control system. , 1967, Journal of applied physiology.

[36]  J J Batzel,et al.  Stability of the human respiratory control system I. Analysis of a two-dimensional delay state-space model , 2000, Journal of mathematical biology.

[37]  D. White,et al.  Influence of sleep onset on upper-airway muscle activity in apnea patients versus normal controls. , 1996, American journal of respiratory and critical care medicine.

[38]  K. Foley,et al.  Receptor interactions in modulating ventilatory activity. , 1990, The American journal of physiology.

[39]  N. Ayas,et al.  Hypercapnia can induce arousal from sleep in the absence of altered respiratory mechanoreception. , 2000, American journal of respiratory and critical care medicine.

[40]  D. Hudgel,et al.  Fluctuation in timing of upper airway and chest wall inspiratory muscle activity in obstructive sleep apnea. , 1990, Journal of applied physiology.

[41]  T. Aittokallio,et al.  Analysis of inspiratory flow shapes in patients with partial upper-airway obstruction during sleep. , 2001, Chest.

[42]  P. Suratt,et al.  Upper airway muscle activation is augmented in patients with obstructive sleep apnea compared with that in normal subjects. , 1988, The American review of respiratory disease.

[43]  E. Carson,et al.  Modelling the dynamic ventilatory response to hypoxia in normal subjects. , 1994, Journal of Theoretical Biology.

[44]  Hopf bifurcations and the stability of the respiratory control system. , 1986, Journal of theoretical biology.

[45]  R. Pellegrino,et al.  Lung elastic recoil during breathing at increased lung volume. , 1999, Journal of applied physiology.

[46]  Olli Polo,et al.  Pathogenesis of obstructive sleep apnoea/hypopnoea syndrome , 1994, The Lancet.

[47]  A S Slutsky,et al.  Factors inducing periodic breathing in humans: a general model. , 1982, Journal of applied physiology: respiratory, environmental and exercise physiology.

[48]  L. Glass,et al.  Oscillation and chaos in physiological control systems. , 1977, Science.

[49]  J P Cleave,et al.  The control of ventilation: a theoretical analysis of the response to transient disturbances. , 1984, Journal of theoretical biology.

[50]  P S Crooke,et al.  Patient-ventilator interaction: a general model for nonpassive mechanical ventilation. , 1998, IMA journal of mathematics applied in medicine and biology.

[51]  S. Javaheri A mechanism of central sleep apnea in patients with heart failure. , 1999, The New England journal of medicine.

[52]  P S Crooke,et al.  A general mathematical model for respiratory dynamics relevant to the clinical setting. , 1993, The American review of respiratory disease.

[53]  T. Young,et al.  The occurrence of sleep-disordered breathing among middle-aged adults. , 1993, The New England journal of medicine.

[54]  H Lorino,et al.  Linear modeling of ventilatory mechanics during spontaneous breathing. , 1982, Computers and biomedical research, an international journal.

[55]  D. White,et al.  Effect of wake‐sleep transitions and rapid eye movement sleep on pharyngeal muscle response to negative pressure in humans , 1999, The Journal of physiology.

[56]  M. Tavola,et al.  Volume and time dependence of respiratory system mechanics in normal anaesthetized paralysed humans. , 2000, The European respiratory journal.

[57]  M. Khoo,et al.  A model-based evaluation of the single-breath CO2 ventilatory response test. , 1990, Journal of applied physiology.

[58]  J. Leiter,et al.  Upper airway shape: Is it important in the pathogenesis of obstructive sleep apnea? , 1996, American journal of respiratory and critical care medicine.

[59]  A. Malhotra,et al.  Upper airway muscle responsiveness to rising PCO(2) during NREM sleep. , 2000, Journal of applied physiology.

[60]  P. Suratt,et al.  Lateral pharyngeal fat pad pressure during breathing in anesthetized pigs. , 1997, Journal of applied physiology.

[61]  W. Mapleson,et al.  Ventilatory assistance and respiratory muscle activity. 1: Interaction in healthy volunteers. , 1998, British Journal of Anaesthesia.

[62]  D. M. Band,et al.  Respiratory oscillations in arterial carbon dioxide tension as a control signal in exercise , 1980, Nature.

[63]  J P Perdrix,et al.  A computer program for automatic measurement of respiratory mechanics in artificially ventilated patients. , 1995, Computer methods and programs in biomedicine.

[64]  D. Shannon,et al.  A minimal mathematical model of human periodic breathing. , 1988, Journal of applied physiology.

[65]  G Kember,et al.  A mathematical analysis of the Grodins model of respiratory control. , 1993, IMA journal of mathematics applied in medicine and biology.

[66]  Erry,et al.  Prospective study of the association between sleep-disordered breathing and hypertension. , 2000, The New England journal of medicine.

[67]  N. Douglas,et al.  Management of obstructive sleep apnoea/hypopnoea syndrome , 1994, The Lancet.

[68]  B. Vielle A new explicit stability criterion for human periodic breathing<--RID="*"--><--ID="*" This research was supported by grants from DRED (96-920).--> , 2000, Journal of mathematical biology.

[69]  A. Harf,et al.  Techniques for measuring respiratory mechanics: an analytic approach with a viscoelastic model. , 1993, Journal of applied physiology.

[70]  R. Pellegrino,et al.  Measurement of pulmonary resistance and dynamic compliance with airway obstruction. , 1998, Journal of applied physiology.

[71]  J. Demongeot,et al.  Entrainment of the respiratory rhythm: a new approach. , 1993, Journal of theoretical biology.

[72]  J. Cleave,et al.  Can periodic breathing have advantages for oxygenation? , 1995, Journal of theoretical biology.

[73]  T Aittokallio,et al.  A model of a snorer's upper airway. , 1999, Mathematical biosciences.

[74]  Tero Aittokallio,et al.  Classification of Nasal Inspiratory Flow Shapes by Attributed Finite Automata , 1999, Comput. Biomed. Res..

[75]  P. Lévy,et al.  Comparison of esophageal pressure with pulse transit time as a measure of respiratory effort for scoring obstructive nonapneic respiratory events. , 2000, American journal of respiratory and critical care medicine.

[76]  M. Tafti,et al.  Why don't all heavy snorers have obstructive sleep apnea? , 1991, The American review of respiratory disease.

[77]  C Hendricks,et al.  Changes in inspiratory muscle electrical activity and upper airway resistance during periodic breathing induced by hypoxia during sleep. , 1987, The American review of respiratory disease.