Reversal of central sleep apnea using nasal CPAP.

Based on the theory that obstructive (OSA) and central (CSA) sleep apneas share common pathophysiologic mechanisms, we attempted to treat eight patients with predominantly CSA by continuous positive airway pressure (CPAP). All patients exhibited repetitive episodes of CSA and mixed sleep apneas (MSA) in the supine position with a mean duration of 23.7 +/- 0.7 s and 34.5 +/- 1.3 s, respectively. The pattern of apnea changed when the subject lay in the lateral position. Five patients were observed to develop OSA in the lateral position with a mean duration of 27.2 +/- 1.5 s, while the other three patients snored continuously. High levels of CPAP (range 9.0 to 16.5 cm H2O) prevented all CSA and MSA and resulted in quiet breathing in all eight patients. Intermediate levels of CPAP produced firstly MSA, then purely OSA and/or continuous snoring. Low levels of nasal CPAP also prevented OSA and snoring occurring in the lateral posture in all subjects (range 2.0 to 8.3 cm H2O). Three patients are currently on home CPAP therapy for a range of four to 36 months. We conclude that upper airway collapse in the supine posture has a key role in the induction of CSA. We suggest that a reflex inhibition of respiration through activation of supraglottic mucosal receptors during passive oropharyngeal airway closure caused CSA in these patients.

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)

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.

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.

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.

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.

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.

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.

Obstructive sleep apnea.

This chapter provides an account of obstructive sleep apnea that is designed for clinicians. Current ideas about the mechanism of upper airway obstruction are reviewed, and the clinical features are discussed in a manner intended to facilitate the clinical assessment of such patients. Various forms of treatment are reviewed, with major emphasis given to the use of nasal positive airway pressure, a form of therapy developed by the authors.

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)

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.

Respiratory muscle activity and thoracoabdominal motion during acute episodes of asthma during sleep.

To understand the mechanisms of respiratory system compensation to internal loading during sleep, all-night sleep studies were performed in 10 patients with chronic stable asthma. We used noninvasive measurements to identify the onset of increased airway resistance in sleep. In each sleep study, we recorded arterial oxygen saturation (SaO2) and an array of electromyograms (diaphragm, external intercostal and sternomastoid) as well as thoracoabdominal motion. Only 4 patients developed acute asthma during sleep. A total of 6 such attacks were recorded. The attacks were detected by audible wheeze, augmentation of diaphragm, external intercostal and sternomastoid activity, associated with distinctive changes in thoracoabdominal motion. The duration of these acute asthmatic attacks ranged between 20 and 140 min. One attack started in stage I/II non-rapid-eye-movement (NREM) sleep, 3 in stage III/IV NREM sleep, and 2 in rapid-eye-movement (REM) sleep. Acute asthma in NREM sleep resulted in a paradoxical inward displacement of the abdomen during early inspiration. Attacks occurring during REM sleep resulted in rib cage inward displacement during inspiration. Attacks occurring during REM sleep resulted in rib cage inward displacement during inspiration. Attacks occurring in both NREM and REM sleep did not result in a significant fall in SaO2. We conclude that acute internal respiratory loading during sleep can provoke different compensatory mechanisms in order to provide adequate ventilation in adult asthmatics.

Arousal and breathing responses to airway occlusion in healthy sleeping adults.

The arousal and breathing responses to total airway occlusion during sleep were measured in 12 normal subjects (7 males and 5 females) aged 25-36 yr. Subjects slept while breathing through a specially designed nosemask, which was glued to the nose with medical-grade silicon rubber. The lips were sealed together with a thin layer of Silastic. The nosemask was attached to a wide-bore (20 mm ID) rigid tube to allow a constant-bias flow of room air from a blower. Total airway occlusion was achieved by simultaneously inflating two rubber balloons fixed in the inspiratory and expiratory pipes. A total of 39 tests were done in stage III/IV nonrapid-eye movement (NREM) sleep in 11 subjects and 10 tests in rapid-eye-movement (REM) sleep in 5 subjects. The duration of total occlusion tolerated before arousal from NREM sleep varied widely (range 0.9-67.0 s) with a mean duration of 20.4 +/- 2.3 (SE) s. The breathing response to occlusion in NREM sleep was characterised by a breath-by-breath progressive increase in suction pressure achieved by an increase in the rate of inspiratory pressure generation during inspiration. In contrast, during REM sleep, arousal invariably occurred after a short duration of airway occlusion (mean duration 6.2 +/- 1.2 s, maximum duration 11.8 s), and the occlusion induced a rapid shallow breathing pattern. Our results indicate that total nasal occlusion during sleep causes arousal with the response during REM sleep being more predictable and with a generally shorter latency than that in NREM sleep.

Upper airway closing pressures in obstructive sleep apnea.

We studied 18 patients with obstructive sleep apnea (OSA). Each subject slept while breathing through the nose with a specially designed valveless breathing circuit. Low levels of continuous positive airway pressure (CPAP) applied through the nose (2.5-15.0 cmH2O) prevented OSA and allowed long periods of stable stage III/IV sleep and rapid-eye-movement (REM) sleep. Externally applied complete nasal occlusion while the upper airway was patent resulted in upper airway closure during inspiration which was identified by a sudden deviation of nasal pressure from tracheal or esophageal pressure. The level of upper airway closing pressure (UACP) did not change throughout the occlusion test, suggesting that upper airway dilator muscles do not respond to asphyxia during sleep. The upper airway was more collapsible during stage I/II non-rapid-eye-movement (NREM) and REM sleep compared with stage III/IV NREM sleep. The pooled mean UACP was 3.1 +/- 0.4 cmH2O in stage I/II NREM, 4.2 +/- 0.2 cmH2O in stage III/IV NREM, and 2.4 +/- 0.2 cmH2O in REM sleep. Nasal occlusion at successively higher levels of CPAP did not alter the level of UACP in stage I/II NREM and REM sleep but resulted in the upper airway becoming more stable in stage III/IV NREM sleep, suggesting a reflex which augments the tone of upper airway dilator muscles.

Upper airway closing pressures in snorers.

We studied 14 subjects who were selected to represent the broad range of severity of snoring: group A, four subjects who gave a history of snoring only when provoked by nasal obstruction or alcohol intake; group B, six subjects who typically snored for long periods each night; and group C, four subjects who snored heavily all night and who typically experienced a few episodes of obstructive apnea (mean apnea index 4 apneas/h). Low levels of nasal continuous positive airway pressure (CPAP) (range, 2.0-6.0 cmH2O; mean, 4.0 cmH2O) prevented snoring. Nasal occlusion caused upper airway closure during inspiratory efforts in all 14 subjects. There was a relationship between the clinical severity of snoring and the upper airway closing pressure (UACP). Upper airway closure occurred at greater suction pressures in group A than in group C but there was overlap between the three categories. The upper airway was consistently more collapsible in rapid-eye-movement sleep than in non-rapid-eye-movement sleep. There was little evidence of breath-by-breath improvement of upper airway stability during sustained asphyxia, the UACP remaining constant despite marked increases in drive to the diaphragm. In five subjects UACP was measured following alcohol intake. Alcohol reduced upper airway stability in all subjects in a dose-dependent manner.

The immediate effects of nasal continuous positive airway pressure treatment on sleep pattern in patients with obstructive sleep apnea syndrome.

We studied the immediate effects of continuous positive airway pressure (CPAP) applied nasally on the pattern of sleep in 12 patients, aged 30-58 years, with obstructive sleep apnea syndrome. All patients demonstrated a moderate to severe syndrome on the control night; apnea index ranged 28-83 apneas/h sleep. Nasal CPAP completely abolished all obstructive apneas and allowed apnea-free breathing in all 12 patients. Nasal CPAP had a marked effect on the sleep pattern. It significantly reduced stage I/II non-rapid eye movement (NREM) sleep and markedly increased stage III/IV NREM and REM sleep on the first treatment night. Stage I/II NREM sleep decreased from a control of 62.7 +/- 2.3% to 29.1 +/- 2.3% on the first treatment night. Stage III/IV NREM sleep increased from a control of 6.7 +/- 1.6% to 31.5 +/- 1.6%. The rebound in this sleep stage was especially marked in 3 patients aged 55-58 years. REM sleep increased from a control of 18.4 +/- 2.0% to 30.6 +/- 2.0% on the first treatment night. There was an increase in REM density. All patients were treated for another 2 nights and their sleep pattern analyzed on the third night. All sleep stages were still significantly different to the control night. The possible mechanisms involved are discussed.