Feasibility of a self-setting CPAP machine.

Auto-setting over-prescribed in six of 20 patients due to severe mouth leak. Mouth leak during CPAP has not previously been quantified, and these results, with leaks of 0.3-1.5 l/second, suggest a mechanism for the dry mouth and nasal symptoms commonly observed with CPAP. Obstructive events were reduced to the normal range in 19 of 20 patients and acceptably reduced in the 20th patient. In the nine nonleakers, mean CPAP pressure was reduced to 54% of the traditionally prescribed pressure. These preliminary results suggest that a self-setting CPAP machine, based on subtle indices of partial obstruction, is practicable in patients without severe mouth leaks.

Nasal continuous positive airway pressure treatment: current realities and future.

Nasal continuous positive airway pressure (CPAP) is a highly effective treatment for obstructive sleep apnea syndrome. The apnea/hypopnea index (AHI) is reduced 10-fold, but the patient dropout rate is up to 30%, and usage is typically < 5 hours per night. Titration, designed to make the best trade-off between effectiveness and side effects, is expensive. Autotitrating devices make this trade-off on a minute-by-minute basis, potentially reducing mean pressure delivery, reducing side effects, and increasing compliance. The aim of this study was to test the effectiveness of the AutoSet self-adjusting nasal CPAP system (ResMed, Sydney, Australia) in eliminating obstructive events and normalizing the arousal index. Forty-five subjects (41 males and 4 females with AHI) values of > 20/hour were recruited, with written informed consent. Subjects slept for a diagnostic night, followed by a treatment night, in the laboratory, using the AutoSet system with full polysomnographic monitoring of respiratory and sleep variables. Arousals were scored using ASDA criteria. Hypopneas were scored when there was a 50% reduction in ventilation for > 10 seconds, associated with a 4% drop in oxygen saturation. For comparison, the ASDA arousal index in 16 normal subjects (without nasal CPAP) is provided. Results are given as mean +/- standard error of the mean. AHI was reduced from 55 +/- 3 to 1.5 +/- 0.35 events/hour (p < 0.0001). The arousal index was reduced from 65 +/- 3 to 18 +/- 2 events/hour (p < 0.0001), identical to the value in the 16 healthy normal subjects. There was a 158% +/- 21% increase in slow-wave sleep (p = 0.01) and a 186% +/- 27% increase in rapid eye movement sleep (p = 0.013). The AutoSet self-adjusting nasal CPAP system adequately treats obstructive sleep apnea syndrome on the first night under laboratory conditions.

Influence of maxillary constriction on nasal resistance and sleep apnea severity in patients with Marfan's syndrome.

BACKGROUND: Marfan's syndrome is associated with a high prevalence of obstructive sleep apnea (OSA). As this syndrome is associated with a characteristic constricted maxilla and high-arched palate, we reasoned that nasal airway constriction and resultant high nasal airway resistance (NAR) may contribute to the development of OSA. Therefore, the aim of this study was to measure NAR in patients with Marfan's syndrome. In addition, we aimed to examine the influence of maxillary morphology on both NAR and the severity of OSA. METHOD: We measured NAR in 13 consecutive patients with Marfan's syndrome and 13 control subjects. NAR was measured by posterior rhinomanometry, and expressed as the inspiratory resistance at a flow of 0.5 L/s. Dental impressions were taken to evaluate maxillary arch morphology, allowing measurement of the following distances: intercuspid (ICD), interpremolar (IPD), intermolar (IMD), and maximum hard palate height (MPH). Ten of the patients and four of the control subjects had previously undergone nocturnal polysomnography. RESULTS: Mean NAR for the Marfan group was more than twice that in the control group (7.7 +/- 1.2 vs 2.9 +/- 0.4 cm H2O/L/s; p < 0.005). The patients also had marked constriction of the maxillary arch compared with control subjects. Two of the lateral maxillary measurements were significantly inversely correlated with NAR. There were significant correlations between various maxillary arch measurements (MPH/ICD, MPH/IPD, MPH/IMD) and the apnea/hypopnea index. CONCLUSION: These data suggest that high NAR is a common feature of Marfan's syndrome. Maxillary constriction with a relatively high hard palate appears to be a major reason for the high NAR. The significant correlations between indexes of maxillary constriction and sleep apnea severity suggest that maxillary morphology may play an important role in the pathophysiology of OSA in Marfan's syndrome.

Waking and genioglossus muscle responses to upper airway pressure oscillation in sleeping dogs.

We studied waking and genioglossus electromyographic (EMGgg) responses to oscillating pressure waves applied to the upper airways of three sleeping dogs. The dogs were previously prepared with a permanent side-hole tracheal stoma and were trained to sleep with a tight-fitting snout mask, hermetically sealed in place, while breathing through a cuffed endotracheal tube inserted through the tracheostomy. Sleep state was determined by behavioral, electroencephalographic, and electromyographic criteria, and EMGgg activity was measured using fine bipolar electrodes inserted directly into the muscle. Oscillatory pressure waves of 30 Hz and +/- 3 cmH2O (tested at atmospheric and subatmospheric upper airway pressures) were applied at the dog's nostrils or larynx, either constantly for a period of 1 min or in 0.5-s bursts. We found that the pressure stimulus had two major effects. First, it was a potentially powerful arousal-promoting stimulus. Arousal occurred in 78% of tests in slow-wave sleep (SWS) and 55% of tests in rapid-eye-movement (REM) sleep, with swallowing and sighing accompanying many of the arousals. Second, it produced an immediate and sustained augmentation of EMGgg, in wakefulness, SWS, and REM sleep. We conclude that oscillatory pressure waves in the upper airway, as found in snoring, produce reflex responses that help maintain upper airway patency during sleep. Loss of this type of reflex might contribute to the onset of obstructive sleep apnea in chronic snorers.

Effects of upper airway pressure on abdominal muscle activity in conscious dogs.

We have examined arousal and abdominal muscle electromyogram (EMGabd) responses to upper airway pressure stimuli during physiological sleep in four dogs with permanent side-hole tracheal stomata. The dogs were trained to sleep with a tightly fitting snout mask, hermetically sealed in place, while breathing through a cuffed endotracheal tube inserted through the tracheostomy. Sleep stage was determined by behavioral and electroencephalographic criteria. EMGabd activity was measured using bipolar fine-wire electrodes inserted into the abdominal muscle layers. Static increases or decreases in upper airway pressure (+/- 6 cmH2O), when applied at the snout mask or larynx (upper trachea), caused an immediate decrease in EMGabd on the first two to three breaths; EMGabd usually returned to control levels within the 1-min test interval. In contrast, oscillatory pressure waves at 30 Hz and +/- 3 cmH2O amplitude (or -2 to -8 cmH2O amplitude) produced an immediate and sustained reduction in IMGabd in all sleep states. Inhibition of EMGabd could be maintained over many minutes when the oscillatory pressure stimulus was pulsed by using a cycle of 0.5 s on and 0.5 s off. Oscillatory upper airway pressures were also found to be powerful arousal-promoting stimuli, producing arousal in 94% of tests in drowsiness and 66% of tests in slowwave sleep. The results demonstrate the presence of breath-by-breath upper airway control of abdominal muscle activity.

Ventilatory response to oxygen after eucapnic hypoxia in conscious dogs.

In humans the ventilatory [minute ventilation (VI)] response to sustained hypoxia is biphasic: an initial brisk increase followed by a decline is usually seen. However, in adult dogs, the ventilatory response to a similar stimulus shows no decline. To evaluate if central ventilatory drive is altered by sustained hypoxia, we measured the lowest ventilation (nadir) as the lowest moving average of seven sequential breaths within 200 s after transition to hyperoxia (100% O2) after 3 different exposures: room air, 4-min (brief) eucapnic hypoxia (arterial O2 saturation = approximately 80%), and 12-min (prolonged) eucapnic hypoxia. The nadir hyperoxic VI after brief hypoxia (2.7 +/- 0.2 l/min) was similar to that after room air (2.6 +/- 0.2 l/min; P > 0.05), with both less than prior room air mean VI (P < 0.05). The nadir after prolonged hypoxia (3.5 +/- 0.3 l/min) was significantly greater than that after brief hypoxia (P < 0.05). This suggests that central ventilatory drive increases in conscious dogs after sustained eucapnic hypoxia. The reason for the difference in central ventilatory response to hypoxia between conscious dogs and adult humans is unexplained.

Tracheal smooth muscle responses to upper airway pressure in conscious dogs.

We studied the influence of changes in pressure applied to the isolated upper airway of four conscious dogs on tracheal smooth muscle tone and breathing pattern. The dogs were prepared with a permanent side-hole tracheal stoma and were trained to sleep with a snout mask hermetically sealed in place while breathing through a cuffed endotracheal tube inserted distally into the tracheal stoma. Changes in tracheal smooth muscle tone were continuously monitored by measuring the pressure in the water-filled cuff that distended the tracheal airway while pressure changes were introduced in the upper airway independently of breathing. Increases or decreases of upper airway pressure (+/- 10 cmH2O) had little effect on tracheal airway smooth muscle tone. In contrast, an oscillating pressure wave at 30 Hz and +/- 3 cmH2O amplitude (or -3 to -7 cmH2O amplitude) caused a marked increase in tracheal airway smooth muscle tone. An elevated tracheal airway tone could be maintained over many minutes when the oscillating pressure stimulus was pulsed so that there was a cycle of 0.5 s on, 0.5 s off. This stimulus did not change the functional residual capacity but resulted in coughing, swallowing, or sighing in 54% of the tests. In the remaining tests, the pressure stimulus produced a rapid, shallow, and erratic breathing pattern. The tracheal airway constrictor response (but not the ventilatory response) was completely abolished by intravenous atropine. We suggest that upper airway vibration is a potentially powerful mechanism of reflex airway smooth muscle constriction.

Ventilatory response to isocapnic hyperoxia.

Breathing O2 for up to 1 h has been shown to either not influence or slightly increase (6-13%) minute ventilation. However, end-tidal PCO2 was not kept constant in these experiments. In nine healthy men, we studied the ventilatory, blood pressure, and heart rate responses to 30 min of normobaric hyperoxia (50% O2) at isocapnic conditions. Hyperoxia led to a 60% increase in mean minute ventilation (P = 0.002), largely due to an increase in mean tidal volume from 0.66 +/- 0.04 (SE) to 0.88 +/- 0.05 liter (P = 0.007). Fifteen minutes after the termination of hyperoxia, minute ventilation was still increased (P = 0.02) compared with baseline, although it was reduced compared with hyperoxia (P = 0.02). Arterial blood gas analyses in six subjects before and during hyperoxia showed an increase in arterial PO2 and O2 saturation but no change in arterial PCO2 or pH. Hyperoxia induced no changes in arterial blood pressure or heart rate. We conclude that 1) isocapnic hyperoxia stimulates respiration markedly, an effect that is approximately five times higher than previously measured; 2) the increase in ventilation induced by hyperoxia does not affect arterial blood pressure and heart rate; and 3) in experiments using hyperoxia, its effect on breathing and subsequently on PCO2 has to be taken into account.

Breathing route and resistive loading: influence on ventilatory response to hypoxia in conscious dogs.

Unlike normal humans, the tracheostomized conscious dog does not show ventilatory adaptation in response to sustained isocapnic hypoxia. To determine whether this phenomenon is a result of the breathing route or the relatively low airflow resistance of tracheostomy breathing, we evaluated the ventilatory response to sustained isocapnic hypoxia (20 min; arterial oxyhemoglobin saturation = 80%) in five awake dogs during nasal-oral (mask) breathing, tracheal breathing, and tracheal breathing with added matched resistance of upper airway breathing. Mask breathing, like unloaded tracheal breathing, was associated with a consistent level of hyperventilation during the entire hypoxic exposure period. However, mask breathing was always less (P < 0.05) than that found during unloaded tracheal breathing. Loaded tracheal breathing during hypoxia resulted in initial hyperventilation similar to that of unloaded tracheal breathing followed by a "roll off" to a lower minute ventilation similar to that of mask breathing. Our findings demonstrate that ventilatory adaptation is only present during loaded tracheal breathing in dogs and suggest that the breathing route and upper airway resistive loading may play roles in ventilatory adaptation.

Increased normoxic ventilation induced by repetitive hypoxia in conscious dogs.

To determine if a long-lasting increase in normoxic ventilatory drive is induced in conscious animals by repetitive hypoxia, we examined the normoxic [arterial O2 saturation (SaO2) > 93%] ventilatory response following successive episodes of 2-min eucapnic hypoxic challenges (SaO2 = 80%) in awake tracheotomized dogs. End-tidal CO2 was maintained at the resting level during and after repetitive hypoxia. The experimental protocol was performed twice in each of five dogs on separate days. To determine if changes in normoxic ventilation occurred between episodes of repetitive hypoxia, data were compared from six periods (epochs) for all experiments. The mean minute ventilation (VI) during three normoxic periods between episodes of intermittent hypoxia was 135, 154, and 169% of control (P < 0.05). VI during a 30-min recovery period was still higher at 183 and 172% of control (P < 0.05). Normoxic VI between hypoxic and recovery periods was significantly higher than the corresponding values in sham experiments. Our results indicate that a long-lasting increase in normoxic ventilation can be evoked in an awake unanesthetized dog by a short exposure to repetitive hypoxia.

Effect of different levels of hyperoxia on breathing in healthy subjects.

We have recently shown that breathing 50% O2 markedly stimulates ventilation in healthy subjects if end-tidal PCO2 (PETCO2) is maintained. The aim of this study was to investigate a possible dose-dependent stimulation of ventilation by O2 and to examine possible mechanisms of hyperoxic hyperventilation. In eight normal subjects ventilation was measured while they were breathing 30 and 75% O2 for 30 min, with PETCO2 being held constant. Acute hypercapnic ventilatory responses were also tested in these subjects. The 75% O2 experiment was repeated without controlling PETCO2 in 14 subjects, and in 6 subjects arterial blood gases were taken at baseline and at the end of the hyperoxia period. Minute ventilation (VI) increased by 21 and 115% with 30 and 75% isocapnic hyperoxia, respectively. The 75% O2 without any control on PETCO2 led to 16% increase in VI, but PETCO2 decreased by 3.6 Torr (9%). There was a linear correlation (r = 0.83) between the hypercapnic and the hyperoxic ventilatory response. In conclusion, isocapnic hyperoxia stimulates ventilation in a dose-dependent way, with VI more than doubling after 30 min of 75% O2. If isocapnia is not maintained, hyperventilation is attenuated by a decrease in arterial PCO2. There is a correlation between hyperoxic and hypercapnic ventilatory responses. On the basis of data from the literature, we concluded that the Haldane effect seems to be the major cause of hyperventilation during both isocapnic and poikilocapnic hyperoxia.

Ventilation and arousal responses to hypercapnia in normal sleeping humans.

We measured arousal and ventilatory responses to rebreathing from a small bag, initially approximately 7% CO2 in 40% O2, via a nose mask in 13 normal human adults. With deepening non-rapid-eye-movement sleep (NREM), males aroused at increasing alveolar PCO2 (mean +/- SE: stage II 58.6 +/- 1.7, stage III 61.2 +/- 1.0, stage IV 63.8 +/- 0.8 Torr), whereas in rapid-eye-movement sleep (REM), arousal alveolar PCO2 was 57.7 +/- 0.7 Torr, i.e., much lower than in stage III and IV NREM. Females showed no significant change in arousal alveolar PCO2, (II 57.6 +/- 0.9, III 57.3 +/- 1.3, IV 59.4 +/- 0.9, REM 56.3 +/- 1.0 Torr). Male ventilatory response was 2.5 +/- 0.1 (SE) 1 X min-1 X Torr-1 and fell by 49% in NREM (1.29 +/- 0.13) and by 69% in REM (0.78 +/- 0.18). Female response was little affected by state, being similar to male NREM response (wake 1.39 +/- 0.14, NREM 1.40 +/- 0.13, REM 1.11 +/- 0.26 1 X min-1 X Torr-1). In NREM tests, there was no change in sleep state until arousal, whereas in REM, subjects awoke abruptly with the onset of rebreathing (11 cases), showed a transient arousal with onset but continued in REM until final arousal (21 cases), or changed to NREM at onset (2 cases). These arousal results contrast sharply with findings in tracheostomized dogs and in obstructive sleep apnea syndrome, where asphyxic arousal is later in REM than in NREM, suggesting that the events at test onset in REM in the present study may be related to upper airway sensitivity to CO2 specific to REM.

Ventilatory and arousal responses to hypoxia in sleeping humans.

We measured ventilatory and arousal responses to progressive eucapnic hypoxia during wakefulness, nonrapid-eye-movement (NREM) sleep, and rapid-eye-movement (REM) sleep using a progressive isocapnic rebreathing method. Nine healthy adults (4 female, 5 male) slept with a mask glued to the face with medical silicone rubber and breathed from a closed valveless biased flow circuit, including an in-line bag-in-box and a variable soda-lime absorber. Progressive hypoxia was induced by consumption of oxygen and by gradual replacement of circuit volume with nitrogen. Tidal volume was measured by electrical integration of the flow signal from a pneumotach on the box. Arterial hemoglobin oxygen saturation (SaO2) was measured with an ear oximeter and end-tidal CO2 tension (PetCO2) was measured continuously and kept constant by variable absorption. Sleep state was identified using standard criteria with 2 channels each of EEG, submental EMG, and EOG. There was marked variability in arousal level both in NREM and REM sleep, with subjects failing to awaken by 70% SaO2, our previously agreed safety limit, on 12 of 26 NREM tests, and 7 of 15 REM tests. During wakefulness, the mean slope +/- SEM of the ventilatory response to hypoxia was 0.68 +/- 0.07 L/min% SaO2 (n = 36, mean PetCO2 = 37.0 mmHg). In NREM sleep, this response decreased to a mean of 0.42 +/- 0.06 L/min/% SaO2 (n = 26, mean PetCO2 = 37.2 mmHg). In REM sleep, the average ventilatory response was further decreased to 0.33 +/- 0.06 L/min/% SaO2 (n = 15, mean PetCO2 = 37.8 mmHg). Analysis of variance showed a significant state-dependent effect on ventilatory response (p less than 0.01). The wake-NREM and wake-REM differences were significantly different (p less than 0.05), but the NREM-REM difference was not (p greater than 0.2). In REM sleep, breath-to-breath variability was marked, and in 2 cases, the response was not significantly different from zero. In all 3 states, the entire ventilatory response was due to increments in tidal volume. We conclude that (1) at normal alveolar CO2 tension, hypoxia is a poor arousal stimulus in humans, both in NREM and REM sleep, and (2) the eucapnic hypoxic response is reduced but present in NREM sleep and similarly reduced but not always present in REM sleep.

Time course of change in ventilatory response to CO2 with long-term CPAP therapy for obstructive sleep apnea.

Nineteen subjects with the obstructive sleep apnea syndrome (10 with daytime arterial CO2 tension 44 mm Hg or higher) were treated with long-term nocturnal continuous positive airway pressure. The ventilatory response to CO2 (Read's method) was measured in triplicate prior to treatment and after 1, 2, 3, 7, and 14 or more nights of therapy. Seven subjects were tested on at least 4 occasions. For each test, slope of the response line and position of the response line (ventilation at a PCO2 of 60 mm Hg) were calculated. The subjects with initial high daytime CO2 showed no change in slope of response with treatment but showed a progressive increase in ventilation at any given degree of PCO2. Ventilation at a PCO2 of 60 mm Hg increased from a mean of 20.0 +/- 1.3 SEM L/min by 8.0 +/- 2.5 SEM L/min after 2 nights of therapy (p less than 0.05, two-way analysis of variance), and by 16.2 +/- 1.9 L/min after 2 wk or more (p less than 0.01). On average, there was no significant change in either slope or position of response in the subjects with initially normal daytime PCO2. We conclude that airway obstruction in sleep (in obstructive sleep apnea syndrome) leads in some subjects to respiratory failure in the daytime, with a left shift in the ventilatory response to CO2, and that this changes is usually reversible during the next several days.

Remission of severe obesity-hypoventilation syndrome after short-term treatment during sleep with nasal continuous positive airway pressure.

Two patients with the Pickwickian syndrome and with life-threatening sleep hypoxemia were treated with continuous positive airway pressure (CPAP) applied through the nares only during sleep periods. Each patient presented with severe daytime somnolence, disturbed sleep, nocturnal confusion, and daytime awake cardiorespiratory failure (PaCO2, 63 and 55 mmHg). Both patients demonstrated grossly abnormal breathing during sleep with severe sleep hypoxemia, the arterial oxyhemoglobin saturation (SaO2%) falling repetitively to levels below 50%. One patient had a hypoxemic convulsion during the initial sleep evaluation. Low levels (3.5 and 8.0 cm H2O) of continuous positive airway pressure, when applied via a comfortable nose mask, prevented occlusive apnea and obstructive hypopnea during sleep in both patients and maintained steady levels of arterial oxyhemoglobin saturation. There was rapid recovery of mental function and loss of cardiorespiratory failure within 3 days of treatment. After short-term treatment with nocturnal CPAP therapy (23 days and 35 days) both patients were able to sleep, unaided, without sleep-induced upper airway occlusion with arterial oxyhemoglobin levels sustained above 80%. We conclude that nasal CPAP therapy during sleep is an effective noninvasive therapy for patients with the Pickwickian syndrome, and may lead to a stable remission of the underlying severe disordered breathing in sleep.

Detection of apnoeas, hypopnoeas and arousals by the AutoSet in the sleep apnoea/hypopnoea syndrome.

Limited sleep study systems are increasingly being used to diagnose the sleep apnoea/hypopnoea syndrome, but validation is essential and detection of arousal's desirable. One such system (AutoSet) was validated on an event-by-event basis, and the hypothesis that sudden large breaths detected by this system mark arousal from sleep was also examined. Twenty consecutive patients (apnoea/hypopnoea index (AHI) 39+/-6 (SEM)) underwent polysomnography (PSG), which included real-time signals of AutoSet (Version 3.03) scored events. PSG respiratory events were defined using airflow and thoracoabdominal movement and AutoSet events using nasal pressure. All apnoeas were scored by both systems, but 41% more hypopnoeas were scored on PSG and these were clinically significant, with 78% ending in cortical arousal. Twenty per cent of apnoeas and hypopnoeas scored by the AutoSet occurred during wakefulness. Large breaths, defined as a two-thirds increase in ventilation, marked 77% of respiratory-associated but only 9% of spontaneous arousals. Large breaths also marked 48% of "autonomic" arousals following respiratory events without visible electroencephalographic changes. Twenty-seven per cent of large breaths occurred during wakefulness. This study shows that the AutoSet and the standard polysomnographic approach differ in their detection of hypopnoeas. The AutoSet underdetected hypopnoeas during sleep, but also included some hypopnoeas occurring during wakefulness. Detection of large breaths may potentially be useful for identifying respiratory arousals. Detection of periods of wakefulness may improve the accuracy of the system.

Studies of oxygenation during sleep in patients with interstitial lung disease.

The pattern of change in arterial oxyhemoglobin saturation (SaO2%) during sleep was characterized in 13 patients with interstitial lung disease (ILD), 12 of whom had restrictive ventilatory impairment. Four patients snored during sleep. During the studies, 9 patients had unequivocal rapid eye movement (REM) sleep episodes. The total duration of each patient's REM episodes averaged 49 min (range, 26 to 93 min), which was 22 +/- 7% (1SD) of the total sleep duration. Seven of these 9 patients were nonsnorers but had definite falls in SaO2% during REM sleep (mean fall in SaO2%, 8 +/- 3%), and in 6 of them the falls in SaO2% were transient, with a mean duration of 28 +/- 12 s and a total duration of 6.4 +/- 3.9 min or 16 +/- 12% of the total REM sleep duration. The other nonsnorer showed sustained desaturation (SaO2, 80 to 85%) for his entire REM sleep period of 26 min. In the nonsnoring patients, the falls in SaO2% during REM sleep (8 +/- 3%) were usually greater than those occurring during awake exercise (6 +/- 7%). Two snorers had unexpected sleep apnea syndrome (minimal SaO2% during NREM sleep, 83 and 77%, respectively; minimal SaO2% during REM sleep, 58 and 67%, respectively). The other snorers had greater than 10% falls in SaO2% during NREM sleep. The breathing frequency in NREM sleep in patients with ILD (mean, 23 +/- 5 breaths/min) was persistently above the normal range (mean, 15 +/- 0.4 breaths/min). The possibility of sleep hypoxemia should be considered in the management of patients with ILD.

Central sleep apnea is associated with increased ventilatory response to carbon dioxide and hypersecretion of growth hormone in patients with acromegaly.

Although obstructive sleep apnea (OSA) occurs commonly in acromegaly, we have recently reported an unexpectedly high prevalence of central sleep apnea (CSA) in these patients. Acromegalic patients with CSA have increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels compared with their counterparts with OSA. Studies in animals, normal humans, and patients with sleep apnea have suggested that CSA is associated with increased gain of the respiratory control system. To examine the relationship between sleep apnea, respiratory control, and hormonal activity in acromegaly, we performed sleep studies and examined ventilatory responses to hypoxia at resting CO2 (HVR) and 8 mm Hg above resting CO2 (HHVR) and hypercapnia (HCVR) in 54 patients with acromegaly who also underwent detailed endocrine evaluation. Patients with CSA (n = 11) had higher HCVR (3.47 +/- 0.57 L/min/mm Hg) than did patients with obstructive sleep apnea (OSA) (1.86 +/- 0.19, n = 33) and patients without sleep apnea (1.77 +/- 0.21, n = 10). Measures of ventilatory control were all correlated with the mean of 12 hourly GH concentrations, but only HCVR was correlated with IGF-1 levels. Multiple linear regression analysis revealed that HCVR, HHVR, and IGF-1 could explain 39% of the variability in the degree of CSA in acromegalic patients with sleep apnea. We conclude that increased ventilatory responsiveness and elevated hormonal parameters of disease activity both contribute to the pathogenesis of central sleep apnea in acromegaly.

Abdominal muscle activity in conscious dogs: effect of sleep and route of breathing.

Abdominal muscle activity (EMGabd) was studied in 4 adult dogs during wakefulness and sleep. The dogs were previously prepared with a permanent side-hole tracheal stoma, and were trained to sleep with a tightly-fitted snout mask, hermetically sealed in place. They breathed either through a cuffed endotracheal tube inserted distally into the tracheal stoma (tracheal), or through the upper airway, with the tracheal stoma plugged (nasal). Sleep state was determined by behavioural, electroencephalographic and electromyographic criteria. EMGabd activity was measured using fine bipolar needles inserted into the abdominal muscle layers. Expiratory EMGabd augmented progressively from sleep onset to SWS regardless of route of breathing, and without major changes in the animal's ventilation. Maximal EMGabd occurred in SWS during nasal breathing; EMGabd increased from a mean of 16.6 +/- 0.3 mV awake, to 23.8 +/- 0.3 mV in SWS, representing an overall increase of 55.0 +/- 7.5% from the awake level. EMGabd increased similarly during tracheal breathing, with an overall increase of 62.0 +/- 15.4% in SWS. We conclude that the consistent augmentation of expiratory EMGabd activity in sleep indicates that expiration in the dog is an active process, which is enhanced during nasal breathing and NREM sleep.