Arousal pattern following central and obstructive breathing abnormalities in infants and children.

We analyzed the polysomnographic records of 15 children and 20 infants with obstructive sleep apnea (OSA) to examine the interaction between central and obstructive breathing abnormalities and arousal from sleep. Each patient was matched for age with an infant or child who had no OSA. We found that the majority of respiratory events in infants and children was not terminated with arousal. In children, arousals terminated 39.3 +/- 7.2% of respiratory events during quiet sleep and 37.8 +/- 7.2% of events during active (rapid-eye-movement) sleep. In infants, arousals terminated 7.9 +/- 1.0% of events during quiet sleep and 7.9 +/- 1.2% of events during active sleep. In both infants and children, however, respiratory-related arousals occurred more frequently after obstructive apneas and hypopneas than after central events. Spontaneous arousals occurred in all patients with OSA during quiet and active sleep. The frequency of spontaneous arousals was not different between children with OSA and their matched controls. During active sleep, however, infants with OSA had significantly fewer spontaneous arousals than did control infants. We conclude that arousals is not an important mechanism in the termination of respiratory events in infants and children and that electroencephalographic criteria are not essential to determine the clinical severity of OSA in the pediatric population.

Control of ventilation during continuous swallowing.

The upper airway performs three distinct functions that must be coordinated to allow maximal operation of each individual system. We tested the ventilatory response to progressive hypercapnia in seven normal adults during continuous swallowing. Swallowing was induced by oral infusion of water while the subject breathed through the nose. Infusion of 40 ml/min resulted in repetitive swallows (rate: 8.1 +/- 4.1 swallows/min, mean +/- SD), but this did not cause a single incidence of coughing or aspiration. Swallows interrupted inspiration and expiration and resulted in compensatory changes in tidal volume and breathing frequency. Continuous drinking did not significantly change the slope of the ventilatory response to hypercapnia. The test was repeated in three subjects swallowing water infused at 60, 80, and 100 ml/min. The slope of the response was also not significantly different from control in these tests. We conclude that continuous swallowing does not override ventilatory control mechanisms in human adults.

Gustatory stimulation of the oropharynx fails to induce swallowing in the sleeping dog.

BACKGROUND/AIMS: Very little is known about the influence of sleep in initiation of swallowing in response to gustatory stimulation of the oropharynx. The aim of the present study was to examine the effect of sleep on swallowing. METHODS: Studies were performed in a group of four dogs trained to sleep naturally in our laboratory. During nasal breathing, tap water, 0.9% NaCl, 0.5 mol/L glucose, 0.5 mol/L NaHCO3, or acetic acid (pH 5.2) were infused at 0.5 mL/s on the dorsum of the tongue using a special feeding tube. The entire surface of the tongue was mapped for initiation of swallowing in the awake and sleeping animal. RESULTS: Swallowing never occurred during non-rapid eye movement and rapid eye movement sleep. Infusion of a solution either did not cause any reaction, resulting in dribbling of the test fluid through the opening between the jaws, or caused arousal that was occasionally followed by a swallow. Arousal-swallow complex occurred most significantly after application of acid and when the fluid was applied to the posterior tongue area. CONCLUSIONS: Wakefulness is a prerequisite for swallowing.

Effect of sleep and sighing on upper airway resistance in mongrel dogs.

We investigated the effect of sleep and sighing on supratracheal resistance in unrestrained mongrel dogs breathing through the nose by comparing within-breath changes in upper airway pressure-flow relationship in control, sigh, and five postsigh breaths recorded during wakefulness and during non-rapid-eye-movement and rapid-eye-movement sleep. A sigh breath was characterized by a high tidal volume and was typically followed by an apnea of a variable duration. Sleep had little or no effect on supratracheal resistance, measured at peak flow rates, during quiet breathing (awake 7.3 +/- 0.4, non-rapid eye movement 8.3 +/- 0.4, and rapid eye movement 6.8 +/- 0.4 cmH2O.l-1.s). The resistance was identical in the early part of inspiration in control and sigh breaths but increased during the augmented phase of sigh breaths. Resistance at peak inspiratory flow was higher in sigh breaths than in control breaths in all sleep states. The flow-pressure profile of postsigh breaths was identical to that of control breaths in all sleep states. We conclude that upper airway resistance is essentially unaffected by sleep state in the mongrel dog and that sighing increases upper airway resistance regardless of sleep state.

Effect of continuous swallowing on respiration.

We examined the effect of continuous swallowing on breathing pattern and ventilation in 7 adult subjects. Repetitive swallowing was induced by oral infusion of water at a variable rate of 40, 60, 80 or 100 ml/min, while the subject breathed through the nose. The number of swallows increased from a mean of 5.2 (+/- 2.7 SD) swallows/min during the control period to 9.2 +/- 2.0 to 13.7 +/- 2.9 swallows/min during infusion of 40 and 100 ml/min, respectively. The duration of interruption of breathing was bolus volume-dependent, increasing from 0.55 +/- 0.09 sec with a mean bolus volume of 4.6 +/- 1.4 ml to 0.87 +/- 0.23 sec with a bolus volume of 8.1 +/- 1.9 ml. The majority of swallows (73 +/- 12%) interrupted breathing during inspiration. The mean tidal volume, inspiratory and expiratory times during swallowing periods were higher than those recorded during the control period, but the mean level of ventilation was not different from control, at all swallowing frequencies. Repetitive swallowing did not result in a single incidence of aspiration or coughing. We conclude that mechanisms integrating breathing and swallowing allow repetitive swallowing to occur without compromising ventilation, and that these mechanisms perfectly orchestrate between breathing and deglutition to prevent aspiration.

Digital monitoring of sleep-disordered breathing using snoring sound and arterial oxygen saturation.

A new portable digital recorder (SNORESAT) that uses the sound of snoring and arterial oxygen saturation (SaO2) to monitor breathing abnormalities during sleep was constructed and compared in the laboratory with standard overnight polysomnography (PSG). The device digitally records sound from a transducer applied to the chest and SaO2 from a commercially available ear oximeter. A snore is identified when the moving time average of the sound exceeds a threshold voltage level longer than 0.26 s. The stored data are transferred to a personal computer for poststudy analysis. An analysis algorithm identifies a respiratory disturbance event when a quiet period of 10 to 120 s separates two snores and is associated with a fall in SaO2 exceeding 3%. The respiratory disturbance index (RDI), mean apnea duration, mean lowest SaO2, and number of desaturations > 3% are computed. A total of 129 referrals to the sleep apnea outpatient clinic underwent simultaneous all-night recording of PSG and SNORESAT. Using the computed RDI recorded by the SNORESAT, the sensitivity and specificity of the monitor in detecting sleep apnea syndrome (SAS) ranged between 84 and 90% and 95 and 98%, respectively, depending on the PSG value of RDI used to define SAS (range, > or = 7 to > or = 20 events/h). Using a PSG value of RDI > or = 10, or > or = 20 RD/h as the definition for SAS, the prevalence of SAS in the referral population was 45 and 31%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of sleep on changes in breathing pattern accompanying sigh breaths.

We studied the effect of sleep on the characteristics of sigh breaths and the associated changes in breathing pattern in breaths following spontaneous sighs in 4 unrestrained dogs with an intact upper airway. The sigh breath was characterized by its large tidal volume (VT), long TI and TE in comparison with the control breath. The volume of the sigh breath was larger in awake sighs than in those recorded during non-REM (NREM) and REM sleep. The strength of Hering-Breuer reflex as determined by duration of the post-sigh apnea was similar in NREM and REM sleep. Sighs occurring during wakefulness, NREM and REM sleep were associated with augmented activity of the parasternal muscles during inspiration, and a persistent tonic abdominal muscle activity during the expiratory period. Breathing pattern in the post-sigh period was characterized by a smaller VT and longer TE in the first post-sigh breath in all sleep states (compared with the control breath), but the pattern returned to control level within the second or third post-sigh breath in both NREM and REM sleep. Sighs did not precipitate periodic breathing or other forms of abnormal breathing patterns in either wakefulness or sleep. We conclude that the respiratory control mechanisms stabilizing breathing after a sigh in the awake dog are intact in NREM and REM sleep.

Effect of route of breathing on the ventilatory and arousal responses to hypercapnia in awake and sleeping dogs.

1. The influence of the upper airway on the ventilatory and arousal responses to hypercapnia in wakefulness and sleep was investigated using a chronic animal model. 2. Experiments were performed in five unrestrained dogs trained to sleep naturally in the laboratory. The animal rebreathed through a chronic tracheostoma (thus excluding the upper airway from the breathing circuit), or through the snout (intact upper airway). Resistance to breathing and volume of dead space during quiet tracheal breathing were matched to those in quiet nasal breathing during wakefulness and sleep. CO2 rebreathing tests were performed during wakefulness, rapid eye movement (REM) and non-REM (NREM) sleep, during nasal and tracheal breathing. 3. The ventilatory response to hypercapnia was significantly lower in nasal breathing compared with tracheal breathing, in all behavioural states. This was due to a smaller tidal volume and lower breathing frequency. 4. The ventilatory response to CO2 was lowest during REM sleep, irrespective of route used for breathing. 5. Alveolar partial pressure of CO2 (PA,CO2) level at arousal was identical in NREM nasal and tracheal rebreathing tests. Differences in PA,CO2 levels at arousal between NREM and REM sleep were not significant in nasal tests and only marginally different during tracheal breathing. 6. We conclude that nasal breathing influences the hypercapnic ventilatory response in wakefulness and sleep, and that the presence of CO2 in the upper airway does not affect arousal in NREM and REM sleep.

Site of pharyngeal narrowing predicts outcome of surgery for obstructive sleep apnea.

Uvulopalatopharyngoplasty (UPPP), an operation that enlarges the pharyngeal airway at the level of the soft palate, improves respiratory status during sleep in only 50% of patients with obstructive sleep apnea (OSA). This poor outcome suggests that narrowing of the pharyngeal airway at nonpalatal sites contributes to the obstructive process in many patients with OSA. We have used a novel endoscopic method to identify regions of the passive pharyngeal airway most susceptible to narrowing or complete closure. In order to test the hypothesis that narrowing of the passive airway at the nasopharynx predicts a favorable surgical outcome, we have preoperatively assessed the local mechanics of the passive pharyngeal airway in 18 patients with OSA undergoing UPPP. The patient population was prospectively divided into two groups: an exclusively nasopharyngeal (ENP) group, consisting of patients exhibiting narrowing only in the nasopharynx, and a not exclusively nasopharyngeal (NENP) group, consisting of patients having at least one site of narrowing outside the nasopharynx. The frequency of respiratory disturbances and arousals and the cumulative time in apnea-hypopnea were significantly reduced after surgery for the ENP group, but not for the NENP group. Improvement rate for the ENP group (86%) exceeded that for the NENP group (18%) (p < 0.01). These differences became even greater when selection criteria for the ENP group were made more restrictive (i.e., restricted to the velopharynx) or more liberal (i.e., including secondary narrowing of the oropharynx). Our results show that evaluation of passive pharyngeal mechanics identifies patients with OSA likely to improve after UPPP.

Restructuring of sleep and reversal of REM-induced supraspinal hypotonia of respiratory muscles following bilateral phrenicotomy.

The long-term effect of diaphragm paralysis on respiratory system function is still not clear. We monitored changes in breathing pattern and the sleep/wake cycle in a dog before and after bilateral phrenicotomy. The post-operative observation extended over 6 months. It was noted that minute ventilation increased during wakefulness and non-REM sleep in the initial 4-6 weeks (compared to pre-surgery period), but decreased during REM sleep, mainly due to inhibition of chest wall and abdominal muscles. These episodes resulted in hypoxemia and frequent arousals. Following this period, there was a restructuring of REM sleep, increasing the frequency of REM sleep and reducing the duration of each REM sleep episode. In addition, the enhanced activity of parasternal and abdominal muscles was persistently seen during REM sleep. These changes in breathing and sleep provided stable ventilation during sleep. We conclude that bilateral phrenicotomy restructures breathing and alters sleep/wake cycle to prevent nocturnal hypoxemia. The mechanisms underlying these changes may reflect plasticity in the control of breathing and REM sleep.

Identification of a subsurface area in the ventral medulla sensitive to local changes in PCO2.

The exact location of the central respiratory chemoreceptors sensitive to changes in PCO2 has not yet been determined. To avoid the confounding effects of the cerebral circulation, we used the in vitro brain stem-spinal cord of neonatal rats (1-5 days old) to identify areas within 500 microns of the ventral surface of the medulla where changes in PCO2 evoked a sudden increase in the rate of respiratory neural activity. The preparation was superfused with mock cerebrospinal fluid (CSF) while maintained at constant temperature (26 +/- 1 degrees C) and pH (7.34). Respiratory frequency increased linearly with decreases in superfusate pH (r2 = 0.92, P less than 0.001), indicating that the respiratory circuitry for the detection of CO2 and stimulation of breathing was intact in this preparation. The search for central chemoreceptors was performed with a specially designed micropipette that allowed microejection of 2-10 nl of mock CSF equilibrated with different CO2-O2 gas mixtures. The pipette was advanced in 50- to 100-microns steps by use of a microdrive to a maximum depth of 500 microns from the surface of the ventral medulla. Depending on the location of the micropipette, ejection of CO2-acidified mock CSF at depths of 100-350 microns below the ventral surface of the medulla stimulated neural respiratory output. Using this response as an indication of the location of central respiratory chemoreceptors, we found that chemoreceptive elements were located in a column in the ventromedial medulla extending from the hypoglossal rootlets caudally to an area 0.75 mm caudal to VI nerve in the rostral medulla.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of clonidine in obstructive sleep apnea.

The current treatment of choice for obstructive sleep apnea is continuous positive airway pressure. However, not all patients tolerate this form of therapy. We evaluated the effect of clonidine hydrochloride, an alpha 2-adrenergic agonist with REM-suppressant activity, in eight male patients with obstructive sleep apnea. In each patient, sleep-stage distribution and breathing pattern in two all-night sleep studies performed during a 10-day course of clonidine were compared with those of two control and two placebo nights. A dose of 0.2 mg of clonidine administered orally at bedtime totally suppressed REM sleep in two patients. In the other six patients, the same dose decreased percent time spent in REM sleep from a control of 13.4 +/- 1.0 to 8.6 +/- 1.4% (mean +/- SEM, p less than 0.05). The latency to REM sleep increased in the latter group from a control of 129 +/- 9 to 308 +/- 24 min (p less than 0.001). Clonidine had no effect on the frequency and duration of non-REM breathing abnormalities. Under clonidine, the level of nocturnal hypoxemia improved in six patients. This was due to a total suppression of REM and the consequent lack of REM apneas in two patients. In four patients, upper airway obstruction disappeared during period of unsuppressed REM sleep, and SaO2 remained above 90% throughout this sleep stage. Clonidine transformed the pattern of sleep-disordered breathing during unsuppressed REM in the other two patients from that of repetitive obstructive hypopneas associated with persistent hypoxemia to occlusive apneas and cyclical hypoxemia. These results were observed consistently in all patients during both clonidine-sleep studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Respiratory failure and sleep in neuromuscular disease.

Sleep hypoxaemia in non-rapid eye movement (non-REM) and rapid eye movement (REM) sleep was examined in 20 patients with various neuromuscular disorders with reference to the relation between oxygen desaturation during sleep and daytime lung and respiratory muscle function. All the patients had all night sleep studies performed and maximum inspiratory and expiratory mouth pressures (PI and Pemax), lung volumes, single breath transfer coefficient for carbon monoxide (KCO), and daytime arterial oxygen (PaO2) and carbon dioxide tensions (PaCO2) determined. Vital capacity in the erect and supine posture was measured in 14 patients. Mean (SD) PI max at RV was low at 33 (19) cm H2O (32% predicted). Mean PE max at TLC was also low at 53 (24) cm H2O (28% predicted). Mean daytime PaO2 was 67 (16) mm Hg and PaCO2 52 (13) mm Hg (8.9 (2.1) and 6.9 (1.7) kPa). The mean lowest arterial oxygen saturation (SaO2) was 83% (12%) during non-REM and 60% (23%) during REM sleep. Detailed electromyographic evidence in one patient with poliomyelitis showed that SaO2% during non-REM sleep was maintained by accessory respiratory muscle activity. There was a direct relation between the lowest SaO2 value during REM sleep and vital capacity, daytime PaO2, PaCO2, and percentage fall in vital capacity from the erect to the supine position (an index of diaphragm weakness). The simple measurement of vital capacity in the erect and supine positions and arterial blood gas tensions when the patient is awake provide a useful initial guide to the degree of respiratory failure occurring during sleep in patients with neuromuscular disorders. A sleep study is required to assess the extent of sleep induced respiratory failure accurately.

Genioglossus and breathing responses to airway occlusion: effect of sleep and route of occlusion.

We examined the effect of sleep state on the response of genioglossus muscle (EMGgg) activity to total airway occlusion applied at 1) nasal (N) airway [and thus exposing the upper airway (UAW) to pressure changes] and 2) tracheal (T) airway (thus excluding UAW from pressure changes). A total of 233 tests were performed during wakefulness (W), 98 tests in slow-wave sleep (SWS), and 72 tests in rapid-eye-movement (REM) sleep. Prolongation of inspiratory time (TI) of the first occluded effort occurred in all tests irrespective of behavioral state, with the greatest increase seen in awake N tests. Nasal tests augmented EMGgg activity in the first occluded breath and produced a linear increase in EMGgg during occlusion. The EMGgg activity at any given time during nasal occlusion in SWS was less than that recorded during W tests. There was a marked reduction in EMGgg response to N occlusion during REM sleep. The EMGgg activity during awake T tests was significantly less than that of N tests at any given time during occlusion. There was no relationship between the level of EMGgg activity and asphyxia in T tests performed during SWS and REM sleep. Nasal tests decreased the force generated by the inspiratory pump muscles and the central drive to breathing compared with T tests. These results confirm the important role of the UAW in regulating breathing pattern and indicate that both immediate and progressive load-compensating responses during nasal occlusion are influenced by information arising from the UAW.

Arousal responses to airway occlusion in sleeping dogs: comparison of nasal and tracheal occlusions.

Previous studies have shown that the arousal threshold to hypoxia, hypercapnia, and tracheal occlusions is greatly depressed in rapid-eye-movement (REM) sleep compared with slow-wave sleep (SWS). The aim of this study was to compare the arousal thresholds in SWS and REM sleep in response to an upper airway pressure stimulus. We compared the waking responses to tracheal (T) vs. nasal (N) occlusion in four unanesthetized, naturally sleeping dogs. The dogs either breathed through a tracheal fistula or through the snout using a fiberglass mask. A total of 295 T and 160 N occlusion tests were performed in SWS and REM sleep. The mean time to arousal during N and T tests was variable in the same dog and among the dogs. The mean time to arousal in SWS-tracheal occlusion was longer than that in N tests in only two of the four dogs. The total number of tests inducing arousal within the first 15 s of SWS-nasal occlusion tests was significantly more than that of T tests (N: 47%; T: 27%). There was a marked depression of arousal within the initial 15 s of REM sleep in T tests compared with N tests (N: 21%; T: 0%). The frequency of early arousals in REM tests was less than that of SWS for both N and T tests. The early arousal in N occlusion is in sharp contrast to the well-described depressed arousal responses to hypoxia, hypercapnia, and asphyxia. This pattern of arousal suggests that the upper airway mechanoreceptors may play an important role in the induction of an early arousal from nasal occlusion.

Upper airway dilating forces during wakefulness and sleep in dogs.

We measured the pressure within an isolated segment of the upper airway in three dogs during wakefulness (W), slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. Measurements were taken from a segment of the upper airway between the nares and midtrachea while the dog breathed through a tracheostoma. These pressure changes represented the sum of respiratory-related forces generated by all muscles of the upper airway. The mean base-line level of upper airway pressure (Pua) was -0.5 +/- 0.03 cmH2O during W, increased by a mean of 2.1 +/- 0.2 cmH2O during SWS, and was variable during REM sleep. The mean inspiratory-related phasic change in Pua was -1.2 +/- 0.1 cmH2O during wakefulness. During SWS, this phasic change in Pua decreased significantly to a mean of -0.9 +/- 0.1 cmH2O (P less than 0.05). During REM sleep, the phasic activity was extremely variable with periods in which there were no fluctuations in Pua and others with high swings in Pua. These data indicate that in dogs the sum of forces which dilate the upper airway during W decreases during SWS and REM sleep. The consistent coupling between inspiratory drive and upper airway dilatation during wakefulness persists in SWS, but is frequently uncoupled during REM sleep.

Influence of negative pressure applied to the upper airway on the breathing pattern in unanesthetized awake dogs.

We examined the influence of changes in upper airway pressure on the breathing pattern in 5 unanesthetized awake dogs. The dogs breathed through an endotracheal tube or through a comfortably fitting fiberglass snout mask. With matched resistances and volume of the dead space, the inspiratory duration, tidal volume, and minute ventilation were higher during nasal breathing compared to tracheal breathing. Nasal and tracheal occlusion produced prolongation of inspiration in the first occluded breathing attempt, but the prolongation was more marked in nasal occlusion tests. Augmentation of genioglossus muscle activity occurred on the first occluded breath in nasal but not tracheal occlusion. In another series of experiments, negative pressure was applied to the isolated upper airway while the dog breathed through a tracheostomy tube. Negative pressure caused a prolongation of inspiratory duration which was proportional to the level of the applied pressure. However, the prolongation of inspiratory duration was significantly more marked when application of negative pressure was timed simultaneously with tracheal occlusion. Our results demonstrate that the upper airway has a powerful effect on the control of breathing, which becomes more evident during tracheal occlusion.