Genioglossus muscle activity at rest and in response to brief hypoxia in healthy men and women.

Obstructive sleep apnea (OSA) is more common in men than in women for reasons that are not clearly understood. An underlying difference between men and women in the respiratory-related neural control of upper airway dilator muscles has been suggested as a possible reason for the gender difference. We have compared three aspects of upper airway dilator muscle function in healthy men and women: 1) resting inspiratory genioglossus electromyogram (EMGgg) activity, 2) the respiratory EMGgg "afterdischarge" after a brief hypoxic stimulus, and 3) the relationship between the EMGgg and pharyngeal airway pressure. Inspired minute ventilation (VI), epiglottic pressure (P(epi)), and EMGgg and diaphragm EMG (EMGdi) activity were measured in 24 subjects (12 men, 12 women in the luteal menstrual phase) and were compared between genders while lying supine awake. Every 7-8 min over 2 h, subjects were exposed to 45-s periods of isocapnic hypoxia (9% O(2) in N(2)) that were abruptly terminated with one breath of 100% O(2). The relationship between P(epi) and EMGgg activity was also compared between genders. The results of 117 trials with satisfactory end-tidal PCO(2) control and no sighs or swallows are reported. There was no gender difference in the resting level of peak inspiratory EMGgg [3.7 +/- 0.8 (women) vs. 3.2 +/- 0.6% maximal activity (men)]. Repeated-measures ANOVA showed no gender or gender-by-time interaction effect between men and women in VI or EMGgg or EMGdi activity during or after the hypoxic stimulus. The relationship between P(epi) and EMGgg was not different between men (slope -0.63 +/- 0.20) and women (slope -0.69 +/- 0.33). These results do not support the hypothesis that the higher prevalence of OSA in men is related to an underlying gender difference in respiratory neural control of upper airway dilator muscles.     

Determinants of long-term facilitation in humans during NREM sleep.

Long-term facilitation (LTF) is a prolonged increase in ventilatory motor output after episodic peripheral chemoreceptor stimulation. We have previously shown that LTF is activated during sleep following repetitive hypoxia in snorers (Babcock MA and Badr MS. Sleep 21: 709-716, 1998). The purpose of this study was 1) to ascertain the relative contribution of inspiratory flow limitation to the development of LTF and 2) to determine the effect of eliminating inspiratory flow limitation by nasal CPAP on LTF. We studied 25 normal subjects during stable non-rapid eye movement sleep. We induced 10 episodes of brief repetitive isocapnic hypoxia (inspired O(2) fraction = 8%; 3 min) followed by 5 min of room air. Measurements were obtained during control and at 20 min of recovery (R(20)). During the episodic hypoxia study, inspiratory minute ventilation (Vi) increased from 6.7 +/- 1.9 l/min during the control period to 8.2 +/- 2.7 l/min at R(20) (122% of control; P < 0.05). Linear regression analysis confirmed that inspiratory flow limitation during control was the only independent determinant of the presence of LTF (P = 0.005). Six subjects were restudied by using nasal continuous positive airway pressure to ascertain the effect of eliminating inspiratory flow limitation on LTF. Vi during the recovery period was 97 +/- 10% (P > 0.05). In conclusion, 1) repetitive hypoxia in sleeping humans is followed by increased Vi in the recovery period, indicative of development of LTF; 2) inspiratory flow limitation is the only independent determinant of posthypoxic LTF in sleeping human; 3) elimination of inspiratory flow limitation abolished the ventilatory manifestations of LTF; and 4) we propose that increased Vi in the recovery period was a result of preferential recruitment of upper airway dilators by repetitive hypoxia.     

Long-term facilitation in obstructive sleep apnea patients during NREM sleep.

Repetitive hypoxia followed by persistently increased ventilatory motor output is referred to as long-term facilitation (LTF). LTF is activated during sleep after repetitive hypoxia in snorers. We hypothesized that LTF is activated in obstructive sleep apnea (OSA) patients. Eleven subjects with OSA (apnea/hypopnea index = 43.6 +/- 18.7/h) were included. Every subject had a baseline polysomnographic study on the appropriate continuous positive airway pressure (CPAP). CPAP was retitrated to eliminate apnea/hypopnea but to maintain inspiratory flow limitation (sham night). Each subject was studied on 2 separate nights. These two studies are separated by 1 mo of optimal nasal CPAP treatment for a minimum of 4-6 h/night. The device was capable of covert pressure monitoring. During night 1 (N1), study subjects used nasal CPAP at suboptimal pressure to have significant air flow limitation (>60% breaths) without apneas/hypopneas. After stable sleep was reached, we induced brief isocapnic hypoxia [inspired O(2) fraction (FI(O(2))) = 8%] (3 min) followed by 5 min of room air. This sequence was repeated 10 times. Measurements were obtained during control, hypoxia, and at 5, 20, and 40 min of recovery for ventilation, timing (n = 11), and supraglottic pressure (n = 6). Upper airway resistance (Rua) was calculated at peak inspiratory flow. During the recovery period, there was no change in minute ventilation (99 +/- 8% of control), despite decreased Rua to 58 +/- 24% of control (P < 0.05). There was a reduction in the ratio of inspiratory time to total time for a breath (duty cycle) (0.5 to 0.45, P < 0.05) but no effect on inspiratory time. During night 2 (N2), the protocol of N1 was repeated. N2 revealed no changes compared with N1 during the recovery period. In conclusion, 1) reduced Rua in the recovery period indicates LTF of upper airway dilators; 2) lack of hyperpnea in the recovery period suggests that thoracic pump muscles do not demonstrate LTF; 3) we speculate that LTF may temporarily stabilize respiration in OSA patients after repeated apneas/hypopneas; and 4) nasal CPAP did not alter the ability of OSA patients to elicit LTF at the thoracic pump muscle.     

Geniohyoid muscle activity in normal men during wakefulness and sleep

Reduction in the activity of upper airway "dilator" muscles during sleep may allow the pharyngeal airway to collapse in some individuals. However, quantitative studies concerning the effect of sleep on specific upper airway muscles that may influence pharyngeal patency are sparse and inconclusive. We studied seven normal men (mean age 27, range 22-37 yr) during a single nocturnal sleep study and recorded sleep staging parameters, ventilation, and geniohyoid muscle electromyogram (EMGgh) during nasal breathing throughout the night. Anatomic landmarks for placement of intramuscular geniohyoid recording electrodes were determined from a cadaver study. These landmarks were used in percutaneous placement of wire electrodes, and raw and moving-time-averaged EMGgh activities were recorded. Sleep stage was determined using standard criteria. Stable periods of wakefulness and non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep were selected for analysis. The EMGgh exhibited phasic inspiratory activity during wakefulness and sleep in all subjects. In six of seven subjects, mean and peak inspiratory EMGgh activities were significant (P less than 0.05) reduced during stages 2 and 3/4 NREM sleep and REM sleep compared with wakefulness. This reduction of EMGgh activity was shown to result from a sleep-related decline in the level of tonic muscle activity. Phasic inspiratory EMGgh activity during all stages of sleep was not significantly different from that during wakefulness. Of interest, tonic, phasic, and peak EMGgh activities were not significantly reduced during REM sleep compared with any other sleep stage in any subject. In addition, the slope of onset of phasic EMGgh activity was not different during stage 2 NREM and REM sleep compared with wakefulness in these subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuromuscular and mechanical responses to inspiratory resistive loading during sleep

The purposes of this study were 1) to characterize the immediate inspiratory muscle and ventilation responses to inspiratory resistive loading during sleep in humans and 2) to determine whether upper airway caliber was compromised in the presence of a resistive load. Ventilation variables, chest wall, and upper airway inspiratory muscle electromyograms (EMG), and upper airway resistance were measured for two breaths immediately preceding and immediately following six applications of an inspiratory resistive load of 15 cmH2O.l-1 X s during wakefulness and stage 2 sleep. During wakefulness, chest wall inspiratory peak EMG activity increased 40 +/- 15% (SE), and inspiratory time increased 20 +/- 5%. Therefore, the rate of rise of chest wall EMG increased 14 +/- 10.9% (NS). Upper airway inspiratory muscle activity changed in an inconsistent fashion with application of the load. Tidal volume decreased 16 +/- 6%, and upper airway resistance increased 141 +/- 23% above pre-load levels. During sleep, there was no significant chest wall or upper airway inspiratory muscle or timing responses to loading. Tidal volume decreased 40 +/- 7% and upper airway resistance increased 188 +/- 52%, changes greater than those observed during wakefulness. We conclude that 1) the immediate inspiratory muscle and timing responses observed during inspiratory resistive loading in wakefulness were absent during sleep, 2) there was inadequate activation of upper airway inspiratory muscle activity to compensate for the increased upper airway inspiratory subatmospheric pressure present during loading, and 3) the alteration in upper airway mechanics during resistive loading was greater during sleep than wakefulness.     

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.     

Effect of episodic hypoxia on upper airway mechanics in humans during NREM sleep.

We hypothesized that long-term facilitation (LTF) is due to decreased upper airway resistance (Rua). We studied 11 normal subjects during stable non-rapid eye movement sleep. We induced brief isocapnic hypoxia (inspired O(2) fraction = 8%) (3 min) followed by 5 min of room air. This sequence was repeated 10 times. Measurements were obtained during control, hypoxia, and at 20 min of recovery (R(20)) for ventilation, timing, and Rua. In addition, nine subjects were studied in a sham study with no hypoxic exposure. During the episodic hypoxia study, inspiratory minute ventilation (VI) increased from 7.1 +/- 1.8 l/min during the control period to 8.3 +/- 1.8 l/min at R(20) (117% of control; P < 0.05). Conversely, there was no change in diaphragmatic electromyogram (EMG(dia)) between control (16.1 +/- 6.9 arbitrary units) and R(20) (15.3 +/- 4.9 arbitrary units) (95% of control; P > 0.05). In contrast, increased VI was associated with decreased Rua from 10.7 +/- 7.5 cmH(2)O. l(-1). s during control to 8.2 +/- 4.4 cmH(2)O. l(-1). s at R(20) (77% of control; P < 0.05). No change was noted in VI, Rua, or EMG(dia) during the recovery period relative to control during the sham study. We conclude the following: 1) increased VI in the recovery period is indicative of LTF, 2) the lack of increased EMG(dia) suggests lack of LTF to the diaphragm, 3) reduced Rua suggests LTF of upper airway dilators, and 4) increased VI in the recovery period is due to "unloading" of the upper airway by LTF of upper airway dilators.     

Episodic hypoxia induces long-term facilitation of neural drive to tongue protrudor and retractor muscles.

Hypoxic episodes can evoke a prolonged augmentation of inspiratory motor output called long-term facilitation (LTF). Hypoglossal (XII) LTF has been assumed to represent increased tongue protrudor muscle activation and pharyngeal airway dilation. However, recent studies indicate that tongue protrudor and retractor muscles are coactivated during inspiration, a behavior that promotes upper airway patency by reducing airway compliance. These experiments tested the hypothesis that XII LTF is manifest as increased inspiratory drive to both tongue protrudor and retractor muscles. Neurograms were recorded in the medial XII nerve branch (XIIMED; contains tongue protrudor motor axons), the lateral XII nerve branch (XIILAT; contains tongue retractor motor axons), and the phrenic nerve in anesthetized, vagotomized, paralyzed, ventilated male rats. Strict isocapnia was maintained for 60 min after five 3-min hypoxic episodes (arterial Po(2) = 35 +/- 2 Torr) or sham treatment. Peak inspiratory burst amplitude showed a persistent increase in XIIMED, XIILAT, and phrenic nerves during the hour after episodic hypoxia (P < 0.05 vs. sham). This effect was present regardless of the quantification method (e.g., % baseline vs. percent maximum); however, comparisons of the relative magnitude of LTF between neurograms (e.g., XIIMED vs. XIILAT) varied with the normalization procedure. There was no persistent effect of episodic hypoxia on inspiratory burst frequency (P > 0.05 vs. sham). These data demonstrate that episodic hypoxia induces LTF of inspiratory drive to both tongue protrudor and retractor muscles and underscore the potential contribution of tongue muscle coactivation to regulation of upper airway patency.     

Long-term facilitation of upper airway muscle activities in vagotomized and vagally intact cats

Mateika, J. H., and R. F. Fregosi. Long-termfacilitation of upper airway muscle activities in vagotomized andvagally intact cats. J. Appl. Physiol.82(2): 419-425, 1997.The primary purpose of the presentinvestigation was to determine whether long-term facilitation (LTF) ofupper airway muscle activities occurs in vagotomized and vagally intactcats. Tidal volume and diaphragm, genioglossus, and nasal dilatormuscle activities were recorded before, during, and after one carotidsinus nerve was stimulated five times with 2-min trains of constantcurrent. Sixty minutes after stimulation, nasal dilator andgenioglossus muscle activities were significantly greater than controlin the vagotomized cats but not in the vagally intact cats. Tidalvolume recorded from the vagotomized and vagally intact cats wassignificantly greater than control during the poststimulation period.In contrast, diaphragm activities were not significantly elevated inthe poststimulation period in either group of animals. We conclude that1) LTF of genioglossus and nasaldilator muscle activities can be evoked in vagotomized cats;2) vagal mechanisms inhibit LTF inupper airway muscles; and 3) LTF canbe evoked in accessory inspiratory muscles because LTF of inspiredtidal volume was greater than LTF of diaphragm activity.

     

Collapsibility of the human upper airway during normal sleep

Upper airway resistance (UAR) increases in normal subjects during the transition from wakefulness to sleep. To examine the influence of sleep on upper airway collapsibility, inspiratory UAR (epiglottis to nares) and genioglossus electromyogram (EMG) were measured in six healthy men before and during inspiratory resistive loading. UAR increased significantly (P less than 0.05) from wakefulness to non-rapid-eye-movement (NREM) sleep [3.1 +/- 0.4 to 11.7 +/- 3.5 (SE) cmH2O.1-1.s]. Resistive load application during wakefulness produced small increments in UAR. However, during NREM sleep, UAR increased dramatically with loading in four subjects although two subjects demonstrated little change. This increment in UAR from wakefulness to sleep correlated closely with the rise in UAR during loading while asleep (e.g., load 12: r = 0.90, P less than 0.05), indicating consistent upper airway behavior during sleep. On the other hand, no measurement of upper airway behavior during wakefulness was predictive of events during sleep. Although the influence of sleep on the EMG was difficult to assess, peak inspiratory genioglossus EMG clearly increased (P less than 0.05) after load application during NREM sleep. Finally, minute ventilation fell significantly from wakefulness values during NREM sleep, with the largest decrement in sleeping minute ventilation occurring in those subjects having the greatest awake-to-sleep increment in UAR (r = -0.88, P less than 0.05). We conclude that there is marked variability among normal men in upper airway collapsibility during sleep.     

Effects of hypoxia on genioglossus and scalene reflex responses to brief pulses of negative upper-airway pressure during wakefulness and sleep in healthy men.

Hypoxia can depress ventilation, respiratory load sensation, and the cough reflex, and potentially other protective respiratory reflexes such as respiratory muscle responses to increased respiratory load. In sleep-disordered breathing, increased respiratory load and hypoxia frequently coexist. This study aimed to examine the effects of hypoxia on the reflex responses of 1) the genioglossus (the largest upper airway dilator muscle) and 2) the scalene muscle (an obligatory inspiratory muscle) to negative-pressure pulse stimuli during wakefulness and sleep. We hypothesized that hypoxia would impair these reflex responses. Fourteen healthy men, 19-42 yr old, were studied on two separate occasions, approximately 1 wk apart. Bipolar fine-wire electrodes were inserted orally into the genioglossus muscle, and surface electrodes were placed overlying the left scalene muscle to record EMG activity. In random order, participants were exposed to mild overnight hypoxia (arterial oxygen saturation approximately 85%) or medical air. Respiratory muscle reflex responses were elicited via negative-pressure pulse stimuli (approximately -10 cmH(2)O at the mask, 250-ms duration) delivered in early inspiration during wakefulness and sleep. Negative-pressure pulse stimuli resulted in a short-latency activation followed by a suppression of the genioglossus EMG that did not alter with hypoxia. Conversely, the predominant response of the scalene EMG to negative-pressure pulse stimuli was suppression followed by activation with more pronounced suppression during hypoxia compared with normoxia (mean +/- SE suppression duration 64 +/- 6 vs. 38 +/- 6 ms, P = 0.006). These results indicate differential sensitivity to the depressive effects of hypoxia in the reflex responsiveness to sudden respiratory loads to breathing between these two respiratory muscles.     

Effect of inspired air temperature on genioglossus activity during nose breathing in awake humans

Experimental data suggest the presence of sensory receptors specific to the nasopharynx that may reflexly influence respiratory activity. To investigate the effects of inspired air temperature on upper airway dilator muscle activity during nose breathing, we compared phasic genioglossus electromyograms (EMGgg) in eight normal awake adults breathing cold dry or warm humidified air through the nose. EMGgg was measured with peroral bipolar electrodes during successive trials of cold air (less than or equal to 15 degrees C) and warm air (greater than or equal to 34 degrees C) nasal breathing and quantified for each condition as percent activity at baseline (room temperature). In four of the subjects, the protocol was repeated after topical nasal anesthesia. For all eight subjects, mean EMGgg was greater during cold air breathing than during baseline (P less than 0.005) or warm air breathing (P less than 0.01); mean EMGgg during warm air breathing was not significantly changed from baseline. Nasal anesthesia significantly decreased the mean EMGgg response to cold air breathing. Nasal airway inspiratory resistance, measured by posterior rhinomanometry in six subjects under similar conditions, was no different for cold or warm air nose breathing [cold 1.4 +/- 0.7 vs. warm 1.4 +/- 1.1 (SD) cmH2O.l-1.s at 0.4 l/s flow]. These data suggest the presence of superficially located nasal cold receptors that may reflexly influence upper airway dilating muscle activity independently of pressure changes in awake normal humans.     

Diaphragm long-term facilitation following acute intermittent hypoxia during wakefulness and sleep

Acute intermittent hypoxia (AIH) elicits a form of respiratory plasticity known as long-term facilitation (LTF). Here, we tested four hypotheses in unanesthetized, spontaneously breathing rats using radiotelemetry for EEG and diaphragm electromyography (Dia EMG) activity: 1) AIH induces LTF in Dia EMG activity; 2) diaphragm LTF (Dia LTF) is more robust during sleep vs. wakefulness; 3) AIH (or repetitive AIH) disrupts natural sleep-wake architecture; and 4) preconditioning with daily AIH (dAIH) for 7 days enhances Dia LTF. Sleep-wake states and Dia EMG were monitored before (60 min), during, and after (60 min) AIH (10, 5-min hypoxic episodes, 5-min normoxic intervals; n = 9), time control (continuous normoxia, n = 8), and AIH following dAIH preconditioning for 7 days (n = 7). Dia EMG activities during quiet wakefulness (QW), rapid eye movement (REM), and non-REM (NREM) sleep were analyzed and normalized to pre-AIH values in the same state. During NREM sleep, diaphragm amplitude (25.1 ± 4.6%), frequency (16.4 ± 4.7%), and minute diaphragm activity (amplitude × frequency; 45.2 ± 6.6%) increased above baseline 0-60 min post-AIH (all P < 0.05). This Dia LTF was less robust during QW and insignificant during REM sleep. dAIH preconditioning had no effect on LTF (P > 0.05). We conclude that 1) AIH induces Dia LTF during NREM sleep and wakefulness; 2) Dia LTF is greater in NREM sleep vs. QW and is abolished during REM sleep; 3) AIH and repetitive AIH disrupt natural sleep patterns; and 4) Dia LTF is unaffected by dAIH. The capacity for plasticity in spinal pump muscles during sleep and wakefulness suggests an important role in the neural control of breathing.     

Fluctuation in timing of upper airway and chest wall inspiratory muscle activity in obstructive sleep apnea

An imbalance in the amplitude of electrical activity of the upper airway and chest wall inspiratory muscles is associated with both collapse and reopening of the upper airway in obstructive sleep apnea (OSA). The purpose of this study was to examine whether timing of the phasic activity of these inspiratory muscles also was associated with changes in upper airway caliber in OSA. We hypothesized that activation of upper airway muscle phasic electrical activity before activation of the chest wall pump muscles would help preserve upper airway patency. In contrast, we anticipated that the reversal of this pattern with delayed activation of upper airway inspiratory muscles would be associated with upper airway narrowing or collapse. Therefore the timing and amplitude of midline transmandibular and costal margin moving time average (MTA) electromyogram (EMG) signals were analyzed from 58 apnea cycles in stage 2 sleep in six OSA patients. In 86% of the postapnea breaths analyzed the upper airway MTA peak activity preceded the chest wall peak activity. In 86% of the obstructed respiratory efforts the upper airway MTA peak activity followed the chest wall peak activity. The onset of phasic electrical activity followed this same pattern. During inspiratory efforts when phasic inspiratory EMG amplitude did not change from preapnea to apnea, the timing changes noted above occurred. Even within breaths the relative timing of the upper airway and chest wall electrical activities was closely associated with changes in the pressure-flow relationship. We conclude that the relative timing of inspiratory activity of the upper airway and chest wall inspiratory muscles fluctuates during sleep in OSA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Upper airway resistance and geniohyoid muscle activity in normal men during wakefulness and sleep

Sleep-related reduction in geniohyoid muscular support may lead to increased airway resistance in normal subjects. To test this hypothesis, we studied seven normal men throughout a single night of sleep. We recorded inspiratory supraglottic airway resistance, geniohyoid muscle electromyographic (EMGgh) activity, sleep staging, and ventilatory parameters in these subjects during supine nasal breathing. Mean inspiratory upper airway resistance was significantly (P less than 0.01) increased in these subjects during all stages of sleep compared with wakefulness, reaching highest levels during non-rapid-eye-movement (NREM) sleep [awake 2.5 +/- 0.6 (SE) cmH2O.l-1.s, stage 2 NREM sleep 24.1 +/- 11.1, stage 3/4 NREM sleep 30.2 +/- 12.3, rapid-eye-movement (REM) sleep 13.0 +/- 6.7]. Breath-by-breath linear correlation analyses of upper airway resistance and time-averaged EMGgh amplitude demonstrated a significant (P less than 0.05) negative correlation (r = -0.44 to -0.55) between these parameters in five of seven subjects when data from all states (wakefulness and sleep) were combined. However, we found no clear relationship between normalized upper airway resistance and EMGgh activity during individual states (wakefulness, stage 2 NREM sleep, stage 3/4 NREM sleep, and REM sleep) when data from all subjects were combined. The timing of EMGgh onset relative to the onset of inspiratory airflow did not change significantly during wakefulness, NREM sleep, and REM sleep. Inspiratory augmentation of geniohyoid activity generally preceded the start of inspiratory airflow. The time from onset of inspiratory airflow to peak inspiratory EMGgh activity was significantly increased during sleep compared with wakefulness (awake 0.81 +/- 0.04 s, NREM sleep 1.01 +/- 0.04, REM sleep 1.04 +/- 0.05; P less than 0.05). These data indicate that sleep-related changes in geniohyoid muscle activity may influence upper airway resistance in some subjects. However, the relationship between geniohyoid muscle activity and upper airway resistance was complex and varied among subjects, suggesting that other factors must also be considered to explain sleep influences on upper airway patency.     

Upper airway and respiratory muscle responses to continuous negative airway pressure

To determine upper airway and respiratory muscle responses to nasal continuous negative airway pressure (CNAP), we quantitated the changes in diaphragmatic and genioglossal electromyographic activity, inspiratory duration, tidal volume, minute ventilation, and end-expiratory lung volume (EEL) during CNAP in six normal subjects during wakefulness and five during sleep. During wakefulness, CNAP resulted in immediate increases in electromyographic diaphragmatic and genioglossal muscle activity, and inspiratory duration, preserved or increased tidal volume and minute ventilation, and decreased EEL. During non-rapid-eye-movement and rapid-eye-movement sleep, CNAP was associated with no immediate muscle or timing responses, incomplete or complete upper airway occlusion, and decreased EEL. Progressive diaphragmatic and genioglossal responses were observed during non-rapid-eye-movement sleep in association with arterial O2 desaturation, but airway patency was not reestablished until further increases occurred with arousal. These results indicate that normal subjects, while awake, can fully compensate for CNAP by increasing respiratory and upper airway muscle activities but are unable to do so during sleep in the absence of arousal. This sleep-induced failure of load compensation predisposes the airways to collapse under conditions which threaten airway patency during sleep. The abrupt electromyogram responses seen during wakefulness and arousal are indicative of the importance of state effects, whereas the gradual increases seen during sleep probably reflect responses to changing blood gas composition.     

Mechanisms of control of alae nasi muscle activity.

Human upper airway dilator muscles are clearly influenced by chemical stimuli such as hypoxia and hypercapnia. Whether in humans there are upper airway receptors capable of modifying the activity of such muscles is unclear. We studied alae nasi electromyography (EMG) in normal men in an attempt to determine 1) whether increasing negative intraluminal pressure influences the activity of the alae nasi muscle, 2) whether nasal airway feedback mechanisms modify the activity of this muscle, and 3) if so, whether these receptor mechanisms are responding to mucosal temperature/pressure changes or to airway deformation. Alae nasi EMG was recorded in 10 normal men under the following conditions: 1) nasal breathing (all potential nasal receptors exposed), 2) oral breathing (nasal receptors not exposed), 3) nasal breathing with splints (airway deformation prevented), and 4) nasal breathing after nasal anesthesia (mucosal receptors anesthetized). In addition, in a separate group, the combined effects of anesthesia and nasal splints were assessed. Under each condition, EMG activity was monitored during basal breathing, progressive hypercapnia, and inspiratory resistive loading. Under all four conditions, both load and hypercapnia produced a significant increase in alae nasi EMG, with hypercapnia producing a similar increment in EMG regardless of nasal receptor exposure. On the other hand, loading produced greater increments in EMG during nasal than during oral breathing, with combined anesthesia plus splinting producing a load response similar to that observed during oral respiration. These observations suggest that nasal airway receptors have little effect on the alae nasi response to hypercapnia but appear to mediate the alae nasi response to loading or negative airway pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory control stability and upper airway collapsibility in men and women with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is two to three times more common in men as in women. The mechanisms leading to this difference are currently unclear but could include gender differences in respiratory stability [loop gain (LG)] or upper airway collapsibility [pharyngeal critical closing pressure (Pcrit)]. The aim of this study was to compare LG and Pcrit between men and women with OSA to determine whether the factors contributing to apnea are similar between genders. The first group of 11 men and 11 women were matched for OSA severity (mean +/- SE apnea-hypopnea index = 43.8 +/- 6.1 and 44.1 +/- 6.6 events/h). The second group of 12 men and 12 women were matched for body mass index (BMI; 31.6 +/- 1.9 and 31.3 +/- 1.8 kg/m2, respectively). All measurements were made during stable supine non-rapid eye movement sleep. LG was determined using a proportional assist ventilator. Pcrit was measured by progressively dropping the continuous positive airway pressure level for three to five breaths until airway collapse. Apnea-hypopnea index-matched women had a higher BMI than men (38.0 +/- 2.4 vs. 30.0 +/- 1.9 kg/m2; P = 0.03), but LG and Pcrit were similar between men and women (LG: 0.37 +/- 0.02 and 0.37 +/- 0.02, respectively, P = 0.92; Pcrit: 0.35 +/- 0.62 and -0.18 +/- 0.87, respectively, P = 0.63). In the BMI-matched subgroup, women had less severe OSA during non-rapid eye movement sleep (30.9 +/- 7.4 vs. 52.5 +/- 8.1 events/h; P = 0.04) and lower Pcrit (-2.01 +/- 0.62 vs. 1.16 +/- 0.83 cmH2O; P = 0.005). However, LG was not significantly different between genders (0.38 +/- 0.02 vs. 0.33 +/- 0.03; P = 0.14). These results suggest that women may be protected from developing OSA by having a less collapsible upper airway for any given degree of obesity.     

Assessment of upper airway stabilizing forces with the use of phrenic nerve stimulation in conscious humans.

Phrenic nerve stimulation (PNS) applied at end-expiration allows the investigation of passive upper airway (UA) dynamic during wakefulness. Assuming that phasic UA dilating/stabilizing forces should modify the UA properties when twitches are applied during inspiration, we compared the UA dynamic responses to expiratory and inspiratory twitches (2 s and 200 ms after expiratory and inspiratory onset, respectively) in nine men (mean age 28 yr). This procedure was repeated with a 2-cm mouth opening provided with a closed mouthpiece. The percentage of flow-limited (FL) twitches was significantly higher when PNS was realized during expiration than during inspiration. Maximal inspiratory flow (Vi(max)) of FL twitches was significantly higher for inspiratory twitches (1,383 +/- 42 and 1,185 +/- 40 ml/s). With mouth aperture, Vi(max) decreased with an increase in the corresponding pharyngeal resistance values, and the percentage of twitch with a FL regimen increased but only for inspiratory twitches. We conclude that 1) UA dynamics are significantly influenced by the inspiratory/expiratory timing at which PNS is applied, 2) the improvement in UA dynamic properties observed from expiratory to inspiratory PNS characterizes the overall inspiratory stabilizing effects, and 3) mouth aperture alters the stability of UA structures during inspiration.     

No evidence for long-term facilitation after episodic hypoxia in spontaneously breathing, anesthetized rats.

Repeated electrical or hypoxic stimulation of peripheral chemoreceptors has been shown to cause a persistent poststimulus increase in respiratory motoneuron activity, termed long-term facilitation (LTF). LTF after episodic hypoxia has been demonstrated most consistently in anesthetized, vagotomized, paralyzed, artificially ventilated rats. Evidence for LTF in spontaneously breathing animals and humans after episodic hypoxia is equivocal and may have been influenced by the awake state of the subjects in these studies. The present study was designed to test the hypothesis that LTF is evoked in respiratory-related tongue muscle and inspiratory pump muscle activities after episodic hypoxia in 10 spontaneously breathing, anesthetized, vagotomized rats. The animals were exposed to three (5-min) episodes of isocapnic hypoxia, separated by 5 min of hyperoxia (50% inspired oxygen). Genioglossus, hyoglossus, and inspiratory intercostal EMG activities, along with respiratory-related tongue movements and esophageal pressure, were recorded before, during, and for 60 min after the end of episodic isocapnic hypoxia. We found no evidence for LTF in tongue muscle (genioglossus, hyoglossus) or inspiratory pump muscle (inspiratory intercostal) activities after episodic hypoxia. Rather, the primary poststimulus effect of episodic hypoxia was diminished respiratory frequency, which contributed to a reduction in ventilatory drive.