Postural effects on pharyngeal protective reflex mechanisms

STUDY OBJECTIVES: Pharyngeal muscle dilators are important in obstructive sleep apnea pathogenesis because the failure of protective reflexes involving these muscles yields pharyngeal collapse. Conflicting results exist in the literature regarding the responsiveness of these muscles during stable non-rapid eye movement sleep. However, variations in posture in previous studies may have influenced these findings. We hypothesized that tongue protruder muscles are maximally responsive to negative pressure pulses during supine sleep, when posterior tongue displacement yields pharyngeal occlusion. DESIGN: We studied all subjects in the supine and lateral postures during wakefulness and stable non-rapid eye movement sleep by measuring genioglossus and tensor palatini electromyograms during basal breathing and following negative pressure pulses. SETTING: Upper-airway physiology laboratory of Sleep Medicine Division, Brigham and Women's Hospital. SUBJECTS/PARTICIPANTS: 17 normal subjects. MEASUREMENTS AND RESULTS: We observed an increase in genioglossal responsiveness to negative pressure pulses in sleep as compared to wakefulness in supine subjects (3.9 percentage of maximum [%max] +/- 1.1 vs 4.4 %max +/- 1.0) but a decrease in the lateral decubitus position (4.1 %max +/- 1.0 vs 1.5 %max +/- 0.4), the interaction effect being significant. Despite this augmented reflex, collapsibility, as measured during negative pressure pulses, increased more while subjects were in the supine position as compared with the lateral decubitus position. While the interaction between wake-sleep state and position was also significant for the tensor palatini, the effect was weaker than for genioglossus, although, for tensor palatini, baseline activity was markedly reduced during non-rapid eye movement sleep as compared with wakefulness. CONCLUSION: We conclude that body posture does have an important impact on genioglossal responsiveness to negative pressure pulses during non-rapid eye movement sleep. We speculate that this mechanism works to prevent pharyngeal occlusion when the upper airway is most vulnerable to collapse eg, during supine sleep.     

Anatomic and physiologic predictors of apnea severity in morbidly obese subjects

STUDY OBJECTIVES: While obesity is the most common risk factor for the development of obstructive sleep apnea, the correlation between measures of obesity and apnea severity is only moderate. We thus attempted to identify anatomic and physiologic predictors of apnea severity. DESIGN: We combined a careful assessment of upper airway anatomy, upper airway physiology, and ventilatory control in a group of obese individuals to identify predictors of apnea severity. Setting: Tertiary care academic medical center. PATIENTS: 14 morbidly obese subjects being evaluated for weight-reduction surgery. INTERVENTIONS: N/A MEASUREMENT AND RESULTS: We found no relationship between obesity (weight or body mass index) and apnea severity (respiratory disturbance index, RDI). However, those with severe apnea (RDI > 30) were found to have higher peak genioglossus EMG (GGEMG) (23.5 +/- 1.9 vs. 14.1 +/- 3.7 %max, p = 0.05) and greater airway collapsibility during pulses of negative pressure (7.6 +/- 0.9 vs. 4.4 -/+/-0.7 cmH2O, p =0.02). Airway collapsibility was significantly associated with RDI (r = 0.62, p < 0.01) as was peak GGEMG (r = 0.55, p < 0.05). Of the anatomic variables airway shape (A-P/lateral ratio) and volume change of the pharyngeal airway between total lung capacity and residual volume were different between those with and without severe apnea. Both correlated with RDI (A-P/lateral ratio: r = 0.70, p < 0.01 and volume change: r = 0.77, p < 0.01). CONCLUSIONS: We believe these findings suggest that specific anatomic and physiologic properties of the airway interact with obesity to predispose to the development of airway collapse during sleep.     

Hypoxia impairs the arousal response to external resistive loading and airway occlusion during sleep

STUDY OBJECTIVES: Sustained hypoxia is a neurocognitive depressant, which has been shown to impair respiratory load sensation. Hypoxia has also been shown to impair arousal in animal models, but the effects of sustained hypoxia on arousal in humans have not been studied. The aim of this study was to assess the effects of sustained hypoxia on arousal from sleep in normal subjects. DESIGN: Twelve normal male subjects (age, 24.3 +/- 1.2 years; body mass index, 24.8 +/- 1.4 kg/m2) were studied during stable stage 2 non-rapid eye movement sleep on 2 separate nights 1 week apart. SETTING: Sleep physiology laboratory. PARTICIPANTS: Normal healthy volunteers. Interventions: Arousal responses to external resistive loads (18 cm H2O x L(-1) x sec(-1)) and occlusions were compared during room-air breathing following sustained normoxia and isocapnic hypoxia (SaO2 approximately 85%). Measurements and Results: Time to arousal and minimum esophageal pressure preceding arousal were measured. Time to arousal was significantly increased following hypoxia compared with normoxia for resistive loads (24.6 + 4.4 seconds vs. 12.6 +/- 1.9 seconds, p = .007) but not occlusions. Minimum esophageal pressure prior to arousal was more negative following hypoxia for both external loads (-16.8 +/- 1.2 vs. -13.5 +/- 1.3 cm H2O, p = .035) and occlusions (-19.6 +/- 2.2 vs. -15.1 +/- 1.5 cm H2O, p = .029). CONCLUSIONS: We conclude that sustained isocapnic hypoxia delays arousal to inspiratory loading during sleep and increases the respiratory arousal threshold. This has implications for disorders characterized by sustained nocturnal hypoxia, such as neuromuscular weakness, chronic obstructive pulmonary disease, obesity-hypoventilation syndrome, and severe obstructive sleep apnea.     

Influence of head extension, flexion, and rotation on collapsibility of the passive upper airway

STUDY OBJECTIVES: To determine the effect of head posture on upper airway collapsibility and site of collapse of the passive human upper airway. DESIGN: Pharyngeal critical closing pressure (Pcrit) and site of airway collapse were assessed during head flexion, extension and rotation in individuals undergoing propofol anesthesia. SETTING: Operating theatre of major teaching hospital. PARTICIPANTS: Fifteen healthy volunteers (8 male), including 7 who were undergoing surgery unrelated to the head or neck. MEASUREMENTS AND RESULTS: Applied upper airway pressure was progressively decreased to induce variable degrees of inspiratory flow limitation and to define Pcrit. Upper airway and oesophageal pressure transducers identified the site of collapse. Genioglossus muscle activity (EMGgg) was assessed using intramuscular fine wire electrodes inserted percutaneously. Data from 3 subjects were excluded from analysis due to persistent EMGgg. In the neutral posture Pcrit was -0.4 +/- 4.4 cm H2O and collapsed most frequently in the velopharyngeal region. Relative to neutral, Pcrit increased to 3.7 +/- 2.9 cm H2O (P < 0.01) and decreased to -9.4 +/- 3.8 cm H2O (P < 0.01) when the head was flexed and extended, respectively but was unchanged by rotation (-2.6 +/- 3.3 cm H2O; n = 10; P = 0.44). The site of collapse varied, in no consistent pattern, with change in head posture in 5 subjects. CONCLUSIONS: Head posture has a marked effect on the collapsibility and site of collapse of the passive upper airway (measured by EMGgg) indicating that controlling head posture during sleep or recovery from anesthesia may alter the propensity for airway obstruction. Further, manipulating head posture during propofol sedation may assist with identification of pharyngeal regions vulnerable to collapse during sleep and may be useful for guiding surgical intervention.     

Effect of expiratory positive airway pressure on sleep disordered breathing

STUDY OBJECTIVES: We sought to determine the effect of expiratory positive airway pressure on end expiratory lung volume (EELV) and sleep disordered breathing in obstructive sleep apnea patients. DESIGN: Observational physiology study PARTICIPANTS: We studied 10 OSA patients during sleep wearing a facial mask. We recorded 1 hour of NREM sleep without treatment (baseline) and 1 hour with 10 cm H2O EPAP in random order, while measuring EELV and breathing pattern. RESULTS: The mean EELV change between baseline and EPAP was only 13.3 mL (range 2-25 mL). Expiratory time was significantly increased with EPAP compared to baseline 2.64 +/- 0.54 vs 2.16 +/- 0.64 sec (P = 0.002). Total respiratory time was longer with EPAP than at baseline 4.44 +/- 1.47 sec vs 3.73 +/- 0.88 sec (P = 0.3), and minute ventilation was lower with EPAP vs baseline 7.9 +/- 4.17 L/min vs 9.05 +/- 2.85 L/min (P = 0.3). For baseline (no treatment) and EPAP respectively, the mean apnea+hypopnea index (AHI) was 62.6 +/- 28.7 and 56.8 +/- 30.3 events per hour (P = 0.4). CONCLUSION: In OSA patients during sleep, the application of 10 cm H2O EPAP led to prolongation of expiratory time with only marginal increases in FRC. These findings suggest important mechanisms exist to avoid hyperinflation during sleep.     

Effect of sleep position and sleep stage on the collapsibility of the upper airways in patients with sleep apnea

Collapsibility of the upper airways has been identified as an important pathogenic factor in obstructive sleep apnea (OSA). Objective measures of collapsibility are pharyngeal critical pressure (Pcrit) and resistance of the upstream segment (Rus). To systematically determine the effects of sleep stage and body position we investigated 16 male subjects suffering from OSA. We compared the measures in light sleep, slow-wave sleep, REM sleep and supine vs. lateral positions. The pressure-flow relationship of the upper airways has been evaluated by simultaneous readings of maximal inspiratory airflow (Vimax) and nasal pressure (p-nCPAP). With two-factor repeated measures ANOVA on those 7 patients which had all 6 situations we found a significant influence of body position on Pcrit (p<0.05) whereas there was no significant influence of sleep stage and no significant interaction between body position and sleep stage. When comparing the body positions Pcrit was higher in the supine than in the lateral positions. During light sleep Pcrit decreased from 0.6 +/- 0.8 cm H2O (supine) to -2.2 +/- 3.6 cm H2O (lateral) (p<0.01), during slow-wave sleep Pcrit decreased from 0.3 +/- 1.4 cm H2O (supine) to -1.7 +/- 2.6 (lateral) (p<0.05) and during REM sleep it decreased from 1.2 +/- 1.5 cm H2O to -2.0 +/- 2.2 cm H2O (p<0.05). Changes in Rus revealed no body position nor sleep-stage dependence. Comparing the different body positions Rus was only significantly higher in the lateral position during REM sleep (p<0.05). The results indicate that collapsibility of the upper airways is not mediated by sleep stages but is strongly influenced by body position. As a consequence lower nCPAP pressure is needed during lateral positions compared to supine positions.     

Oropharyngeal collapse predicts treatment response with oral appliance therapy in obstructive sleep apnea

STUDY OBJECTIVES: To examine whether primary oropharyngeal collapse of the upper airway during sleep predicts treatment success with oral appliance therapy in patients with obstructive sleep apnea. DESIGN: Prospective physiologic study. SETTING: Multidisciplinary sleep disorders clinic in a university teaching hospital. PATIENTS: Twelve treatment-na?ve adult patients with obstructive sleep apnea (apnea-hypopnea index > or = 10/h and at least 2 of the following symptoms: snoring, fragmented sleep, witnessed apneas, or daytime sleepiness). INTERVENTION: Custom-made mandibular advancement splint (MAS). MEASUREMENTS AND RESULTS: A baseline diagnostic polysomnogram confirmed AHI > or = 10 per hour. During the following acclimatization period, a custom-made adjustable MAS was incrementally advanced until maximum comfortable mandibular protrusion was reached. A second polysomnogram with MAS in situ determined efficacy. Following a 1-week washout period, a final sleep study was performed using multisensor catheters (with and without MAS, in random order during the same night) to determine upper-airway closing pressures and the site or sites of upper-airway collapse. MAS resulted in significant improvements, mean +/- SEM, in AHI (22.0 +/- 2.6 vs 9.2 +/- 1.9/h, p < .01) and upper-airway closing pressures during stage 2 non-rapid eye movement sleep (-1.1 +/- 0.3 vs -2.8 +/- 0.5 cm H2O, p < .01). All 4 patients with primary oropharyngeal collapse achieved an AHI < 5 per hour. Only 1 of the 8 patients with primary velopharyngeal collapse achieved an AHI < 5 per hour. Oropharyngeal collapse, compared with velopharyngeal collapse, predicted treatment success with MAS (p < .02). CONCLUSIONS: These preliminary data suggest that primary oropharyngeal collapse of the upper airway during sleep is an important predictor of treatment outcome with MAS therapy.     

Tracheal traction effects on upper airway patency in rabbits: the role of tissue pressure

STUDY OBJECTIVES: To investigate the mechanisms via which lung volume related caudal tracheal traction decreases upper airway collapsibility. DESIGN: Acute physiological study. PARTICIPANTS: 20 male, supine, anesthetised, tracheostomised, spontaneously breathing, NZ white rabbits fitted with a sealed face mask. SETTING: N/A. MEASUREMENTS AND RESULTS: Upper airway extraluminal tissue pressure (ETP) was measured in the lateral (ETPlat) and anterior (ETPant) pharyngeal walls (pressure transducer tipped catheters). Graded traction was applied to the isolated upper airway (n = 17, 0-140 g). Subsequently, inflation and deflation was performed (with and without traction, 48 g, n = 13) with measurement of intraluminal pressure. Upper airway transmural pressure (PTM) was calculated (at closure and reopening) for both ETP sites (PTMlat and PTMant, respectively). A traction force of 144 g decreased ETPlat from 2.6 +/- 0.7 cm H2O (mean +/- SEM) to 2.1 +/- 0.7 cm H2O and ETPant from 1.1 +/- 0.4 cm H2O to 0.8 +/- 0.4 cm H2O (both P < 0.001). Increasing traction decreased closing and reopening pressures by 1.4 +/- 0.2 cm H2O for 48 g of traction (n = 13, P < 0.0001). In addition, 48 g of traction decreased ETPlat (at closure and reopening) by 0.2 +/- 0.05 cm H2O (P < 0.0001), and decreased ETPant by 0.5 +/- 0.1 cm H2O at closing pressure and 0.8 +/- 0.1 cm H2O at reopening (both p < 0.0001). Thus, for 48 g of traction, PTMlat (at closure and reopening) fell by 1.1 +/- 0.2 cm H2O and PTMant (reopening only) fell by 0.9 +/- 0.3 cm H2O (all P < 0.0001). CONCLUSIONS: Since tracheal traction decreased PTMlat and PTMant by a greater amount than ETPlat and ETPant, we conclude that the decrease in upper airway collapsibility mediated by lung volume related caudal tracheal traction is partially explained by reductions in ETP.     

Acute effects of paroxetine on genioglossus activity in obstructive sleep apnea

STUDY OBJECTIVE: To determine the acute effects of paroxetine on genioglossus activity during NREM sleep. DESIGN: A single dose of Paroxetine (40 mg) or placebo was administered four hours before bedtime on nights separated by one week in a double blind randomized crossover manner. The moving time average of genioglossus muscle activity (EMGgg) expressed as a percentage of maximum was measured using a mouthpiece electrode customized for each subject. The peak inspiratory and tonic values of EMGgg and the corresponding esophageal pressure deflections (DP) during the last three occluded breaths of obstructive apneas during NREM sleep were analyzed. SETTING: NA. PARTICIPANTS: 8 adult men with severe obstructive sleep apnea (OSA). INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: Paroxetine increased the peak inspiratory EMGgg (29.8+/-2.4 (SE) versus 24.4+/-2.7 % max, p<0.05) and peak EMGgg/DP ratio (0.78+/-0.12 versus 0.65+/-0.11 % max/cm H2O, p<0.01) but not the tonic EMGgg (11.6+/-0.9 versus 9.8+/-0.7 % max) nor the DP (39.4+/-2.2 versus 38.2+/-2.8 cm H2O). Linear regression analysis of the peak inspiratory EMGgg versus DP relationship showed that paroxetine increased the slope (0.62+/-0.11 versus 0.49+/-0.09 % max/cm H2O, p<0.01). However, the apnea + hypopnea index (paroxetine: 75.2+/-5.5 versus placebo: 73.7+/-6.9 events/hour) did not differ. CONCLUSIONS: Paroxetine augmented peak inspiratory genioglossus activity during NREM sleep but this effect was not sufficient to decrease the frequency of obstructive apnea in this group with severe OSA.     

Measuring end-expiratory lung volume and pulmonary mechanics to detect early lung function impairment in rabbits

We investigated whether end-expiratory lung volume (EELV) or lung mechanical parameters are more sensitive for the detection of a compromised gas exchange during bronchoconstriction and after surfactant depletion. EELV was determined via SF(6) multiple breath wash-outs in mechanically ventilated rabbits while a positive end-expiratory pressure (PEEP) of 1, 3 or 7 cm H(2)O was maintained. Airway resistance (R(aw)) and parenchymal elastance (H) were estimated from the pulmonary input impedance measured at each PEEP level by means of forced oscillations. Measurements were repeated during i.v. methacholine (MCh) infusions and following lung injury induced by saline lavage. MCh induced marked elevations in R(aw), with no significant change in EELV or H at any PEEP. After lavage, the severity of hypoxia was reflected systematically in significant decreases in EELV at all PEEP levels (-42+/-13%, -26+/-4%, and -18+/-5% at 1, 3 and 7 cm H(2)O, respectively), whereas compromised gas exchange was not associated with consistent changes in the mechanical parameters at a PEEP of 7 cm H(2)O (20+/-9% and 14+/-9% in R(aw) and H, respectively; p=0.2). We conclude that R(aw) is the only sensitive indicator for the detection of a compromised lung function during MCh infusions, whereas the estimation of EELV is necessary to follow the progression of a lung injury when a high PEEP level is applied.     

Pharyngeal size in snorers, nonsnorers, and patients with obstructive sleep apnea

We measured pharyngeal cross-sectional area and its change with alterations in lung volume in 10 subjects who snored and had obstructive sleep apnea, 6 subjects who snored and did not have obstructive sleep apnea, and 9 subjects who did not snore. Pharyngeal area was measured with use of an acoustic-reflection technique. We found that snorers with and without sleep apnea had a significantly smaller mean (+/- SE) pharyngeal cross-sectional area (4.1 +/- 0.2 and 3.7 +/- 0.9 cm2, respectively) at functional residual capacity than nonsnorers (5.4 +/- 0.5 cm2, P less than 0.025). When lung volume decreased from functional residual capacity to residual volume, both nonsnorers and snorers with sleep apnea had a decrease in pharyngeal area (from 5.4 +/- 0.5 to 4.5 +/- 0.4 cm2 and 4.1 +/- 0.2 to 3.4 +/- 0.2 cm2, respectively), whereas snorers without sleep apnea had no such decrease, suggesting that their pharynxes were less collapsible at low lung volumes. We conclude that snorers with and without sleep apnea have smaller pharyngeal cross-sectional areas than nonsnorers and that snorers with sleep apnea have a further decrease as lung volume falls.     

Genioglossal muscle response to CO2 stimulation during NREM sleep

STUDY OBJECTIVES: The objective was to evaluate the responsiveness of upper airway muscles to hypercapnia with and without intrapharyngeal negative pressure during non-rapid eye movement (NREM) sleep and wakefulness. DESIGN: We assessed the genioglossal muscle response to CO2 off and on continuous positive airway pressure (CPAP) (to attenuate negative pressure) during stable NREM sleep and wakefulness in the supine position. SETTING: Laboratory of the Sleep Medicine Division, Brigham and Women's Hospital. PATIENTS OR PARTICIPANTS: Eleven normal healthy subjects. INTERVENTIONS: During wakefulness and NREM sleep, we measured genioglossal electromyography (EMG) on and off CPAP at the normal eupneic level and at levels 5 and 10 mm Hg above the awake eupneic level. MEASUREMENTS AND RESULTS: We observed that CO2 could increase upper-airway muscle activity during NREM sleep and wakefulness in the supine position with and without intrapharyngeal negative pressure. The application of nasal CPAP significantly decreased genioglossal EMG at all 3 levels of PETCO2 during NREM sleep (13.0 +/- 4.9% vs. 4.6 +/- 1.6% of maximal EMG, 14.6 +/- 5.6% vs. 7.1 +/- 2.3% of maximal EMG, and 17.3 +/- 6.3% vs. 10.2 +/- 3.1% of maximal EMG, respectively). However, the absence of negative pressure in the upper airway did not significantly affect the slope of the pharyngeal airway dilator muscle response to hypercapnia during NREM sleep (0.72 +/- 0.30% vs. 0.79 +/- 0.27% of maximal EMG per mm Hg PCO2, respectively, off and on CPAP). CONCLUSIONS: We conclude that both chemoreceptive and negative pressure reflex inputs to this upper airway dilator muscle are still active during stable NREM sleep.     

Pentobarbital sedation increases genioglossus respiratory activity in sleeping rats

OBJECTIVE: To determine whether certain sedatives may, by increasing arousal threshold, allow pharyngeal dilator muscle activity to increase more in response to chemical stimuli before arousal occurs. DESIGN, PARTICIPANTS AND INTERVENTIONS: Thirteen chronically instrumented rats were studied during sleep following injections of placebo or sedating doses of pentobarbital (10 mg/kg). Intermittently, inspired CO2 was increased gradually until arousal occurred. MEASUREMENTS AND RESULTS: Maximum genioglossus activity reached before arousal was higher with pentobarbital than placebo (34.5 +/- 24.3 vs 3.7 +/- 2.9mV; P < 0.001) for 2 reasons. First, genioglossus activity was greater during undisturbed sleep before CO2 was applied (23.3 +/- 15.3 vs 2.5 +/- 1.5 mV, P < 0.001). When sleep periods were long, a ramp-like increase in genioglossus activity (GG-Ramp) began and progressed until arousal. GG-Ramps developed with both placebo and pentobarbital but reached higher levels with pentobarbital due to longer sleep periods and faster increase in genioglossus activity during the ramp. GG-Ramps began when diaphragm activity was lowest and progressed despite unchanged diaphragm activity. Second, as hypothesized, the increase in genioglossus activity with CO2 before arousal was greater than with placebo (11.2 +/- 2.5 vs 1.2 +/- 2.5mV; P < 0.05) due to increased arousal threshold. In 27 of 126 CO2 challenges delivered while GG-Ramps were in progress, genioglossus activity paradoxically decreased despite increased diaphragmatic activity. These negative responses occurred randomly in 7 of 13 rats. CONCLUSIONS: In rats: 1) Sedatives may allow genioglossus activity to reach higher levels during sleep. 2) A time-dependent increase in genioglossus activity occurs during undisturbed sleep that is unrelated to chemical drive. 3) Transient hypercapnia may elicit inhibition of genioglossus activity under currently unidentified circumstances.     

Genioglossus reflex inhibition to upper-airway negative-pressure stimuli during wakefulness and sleep in healthy males

During wakefulness, obstructive sleep apnoea patients appear to compensate for an anatomically narrow upper airway by increasing upper airway dilator muscle activity, e.g. genioglossus, at least partly via a negative-pressure reflex that may be diminished in sleep. Previous studies have assessed the negative-pressure reflex using multi-unit, rectified, moving-time-average EMG recordings during brief pulses of negative upper-airway pressure. However, moving-time averaging probably obscures the true time-related reflex morphology, potentially masking transient excitatory and inhibitory components. This study aimed to re-examine the genioglossus negative-pressure reflex in detail, without moving-time averaging. Bipolar fine-wire electrodes were inserted per orally into the genioglossus muscle in 17 healthy subjects. Two upper airway pressure catheters were inserted per nasally. Genioglossus EMG reflex responses were generated via negative-pressure stimuli (∼−10 cmH₂O at the choanae, 250 ms duration) delivered during wakefulness and sleep. Ensemble-averaged, rectified, genioglossus EMG recordings demonstrated reflex activation (onset latency 26 ± 1 ms; peak amplitude 231 ± 29% of baseline) followed by a previously unreported suppression (peak latency 71 ± 4 ms; 67 ± 8% of baseline). Single-motor-unit activity, clearly identifiable in ∼10% of trials in six subjects, showed a concomitant increase in the interspike interval from baseline (26 ± 9 ms, P = 0.01). Genioglossus negative-pressure reflex morphology and amplitude of the initial peak were maintained in non-rapid eye movement (NREM) sleep but suppression amplitude was more pronounced during NREM and declined further during REM sleep compared to wakefulness. These data indicate there are both excitatory and inhibitory components to the genioglossus negative-pressure reflex which are differentially affected by state.     

Pattern of snoring in obstructive sleep apnea patients and in heavy snorers.

We measured respiratory mechanical characteristics during sleep in five heavy, nonapneic snorers (HS) and in five obstructive sleep apnea (OSA) patients. In two HS and in two OSA patients we obtained lateral pharyngeal cineradiographic images during sleep while snoring. Flow limitation preceded all snores in both HS and OSA. Pattern of snoring, hysteresis and temporal relationship between supraglottic pressure (Psg) and flow rate were different in HS and OSA. Maximal flow during snoring was less (p less than 0.05) in OSA (0.18 +/- 0.07 liter/second) than in HS (0.36 +/- 0.06 liter/second). Linear supraglottic resistance during inspiratory snoring was higher, though not significantly, in OSA patients (7.11 +/- 3.01 cm H2O/liter/second) than in HS (4.80 +/- 2.83 cm H2O/liter/second). We conclude that: 1) Snoring is characterized by high frequency oscillations of the soft palate, pharyngeal walls, epiglottis and tongue. 2) Flow limitation appears to be a sine qua non for snoring during sleep. 3) The pattern of snoring is different in OSA and HS. 4) Pharyngeal size during snoring is probably larger in HS than in OSA patients.     

The effect of sleep on reflex genioglossus muscle activation by stimuli of negative airway pressure in humans.

The present study was designed to determine the effect of sleep on reflex pharyngeal dilator muscle activation by stimuli of negative airway pressure in human subjects. Intra-oral bipolar surface electrodes were used to record genioglossus electromyogram (EMG) responses to 500 ms duration pressure stimuli of 0 and -25 cmH2O applied, via a face-mask, in four normal subjects. Stimuli were applied during early inspiration in wakefulness and in periods of non-rapid-eye-movement (non-REM) sleep, defined by electroencephalographic (EEG) criteria. The rectified and integrated EMG responses to repeated interventions were bin averaged for the 0 and -25 cmH2O stimuli applied in wakefulness and sleep. Response latency was defined as the time when the EMG activity significantly increased above prestimulus levels. Response magnitude was quantified as the in ratio of the EMG activity for an 80 ms post-stimulus period to an 80 ms prestimulus period; data from after the subject's voluntary reaction time for tongue protrusion (range, 150-230 ms) were not analysed. Application of the -25 cmH2O stimuli caused genioglossus muscle activation in wakefulness and sleep, but in all subjects response magnitude was reduced in sleep (mean decrease, 61%; range, 52-82%; P = 0.011, Student's paired t test). In addition, response latency was increased in sleep in each subject (mean latency awake, 38 ms; range, 30-50 ms; mean latency asleep, 75 ms; range, 40-110 ms; P = 0.072, Student's paired t test). Application of the -25 cmH2O stimuli caused arousal from sleep on 90% occasions, but in all cases the reflex genioglossus muscle responses (maximum latency, 110 ms) always proceeded any sign of EEG arousal (mean time to arousal, 643 ms; range, 424-760 ms). These results show that non-REM sleep attenuates reflex genioglossus muscle activation by stimuli of negative airway pressure. Attenuation of this reflex by sleep may impair the ability of the upper airway to defend itself from suction collapse by negative pressures generated during inspiration; this may have implications for the pathogenesis of obstructive sleep apnoea.     

Within-Breath Control of Genioglossal Muscle Activation in Humans: Effect of Sleep-Wake State

Pharyngeal dilator muscles are clearly important in the pathogenesis of obstructive sleep apnoea syndrome. Substantial data support the role of a local negative pressure reflex in modifying genioglossal activation across inspiration during wakefulness. Using a model of passive negative pressure ventilation, we have previously reported a tight relationship between varying intrapharyngeal negative pressures and genioglossal muscle activation (GGEMG) during wakefulness. In this study, we used this model to examine the slope of the relationship between epiglottic pressure ( P _epi) and GGEMG, during stable NREM sleep and the transition from wakefulness to sleep. We found that there was a constant relationship between negative epiglottic pressure and GGEMG during both basal breathing (BB) and negative pressure ventilation (NPV) during wakefulness (slope GGEMG/ P _epi 1.86 ± 0.3 vs. 1.79 ± 0.3 arbitrary units (a.u.) cmH₂O⁻¹). However, while this relationship remained stable during NREM sleep during BB, it was markedly reduced during NPV during sleep (2.27 ± 0.4 vs. 0.58 ± 0.1 a.u. cmH₂O⁻¹). This was associated with a markedly higher pharyngeal airflow resistance during sleep during NPV. At the transition from wakefulness to sleep there was also a greater reduction in peak GGEMG seen during NPV than during BB. These data suggest that while the negative pressure reflex is able to maintain GGEMG during passive NPV during wakefulness, this reflex is unable to do so during sleep. The loss of this protective mechanism during sleep suggests that an airway dependent upon such mechanisms (as in the patient with sleep apnoea) will be prone to collapse during sleep.     

Pontine carbachol elicits multiple rapid eye movement sleep-like neural events in urethane-anaesthetized rats.

Microinjection of a cholinergic agonist, carbachol, into the pontine reticular formation of chronically instrumented intact or acutely decerebrate rats and cats has been used extensively to study rapid eye movement sleep mechanisms. In this study, we sought to develop a reduced carbachol model of rapid eye movement sleep-like neural events exhibiting multiple physiological markers of this state, and allowing for the use of invasive electrophysiological techniques. Accordingly, we investigated whether pontine carbachol could produce rapid eye movement sleep-like motor atonia and electrocortical changes in urethane-anaesthetized rats. We recorded cortical and hippocampal electroencephalograms and genioglossus and inspiratory intercostal muscle activities in 13 urethane-anaesthetized, spontaneously breathing, tracheotomized and vagotomized rats. In steady-state periods with high-voltage/low-frequency electroencephalogram activity, carbachol microinjections (15-40 nl, 10 mM) were placed in the medial pontine reticular formation. In 12 rats, carbachol elicited episodes of stereotyped hypotonia of genioglossus but not intercostal muscle activity, typical of rapid eye movement sleep, with a latency and duration of 2.2+/-0.3min (mean+/-S.E.M.) and 11.0+/-2.9 min, respectively. In four of these rats, also similar to rapid eye movement sleep, the major suppression of genioglossus activity (-74+/-9%) was accompanied by electroencephalogram desynchronization, appearance of hippocampal theta rhythm, and a respiratory rate increase (+ 14+/-3%). In the remaining eight rats, the stereotyped suppression of genioglossus activity (-48+/-3%) occurred without electroencephalogram desynchronization and hippocampal theta, and was accompanied by a respiratory rate decrease (-6+/-2%); a pattern of response typical of decerebrate animals. Within a rat, similar patterns of response to repeated carbachol injections at the same anatomical site were obtained. Pontine atropine prevented responses to subsequent carbachol injections. Thus, in urethane-anaesthetized rats, pontine carbachol consistently produced a differential suppression of pharyngeal versus respiratory pump muscle activity, and in a subset of animals, this was also accompanied by cortical and hippocampal electrographic changes typical of rapid eye movement sleep. This shows that complex and stereotyped neuronal events underlying both ascending and descending signs of rapid eye movement sleep can be pharmacologically activated under general anaesthesia. Such a reduced preparation may be useful for studies into the central neuronal mechanisms underlying generation of rapid eye movement sleep; particularly for studies requiring techniques that are difficult to implement in intact, naturally sleeping animals. The acceleration of the respiratory rate observed only when carbachol induced electroencephalogram desynchronization suggests that neural events associated with electrocortical changes contribute to the respiratory rate increases observed in natural rapid eye movement sleep.     

Variability of human upper airway collapsibility during sleep and the influence of body posture and sleep stage

The critical pressure at which the pharynx collapses (Pcrit) is an objective measurement of upper airway collapsibility, an important pathogenetic factor in obstructive sleep apnoea. This study examined the inherent variability of passive Pcrit measurement during sleep and evaluated the effects of sleep stage and body posture on Pcrit. Repeated measurements of Pcrit were assessed in 23 individuals (15 male) with diagnosed obstructive sleep apnoea throughout a single overnight sleep study. Body posture and sleep stage were unrestricted. Applied upper airway pressure was repetitively reduced to obtain multiple measurements of Pcrit. In 20 subjects multiple measurements of Pcrit were obtained. The overall coefficient of repeatability for Pcrit measurement was 4.1 cm H₂O. Considering only the lateral posture, the coefficient was 4.8 cm H₂O. It was 3.3 cm H₂O in the supine posture. Pcrit decreased from the supine to lateral posture [supine mean 2.5 cm H₂O, 95% confidence interval (CI) 1.4–3.6; lateral mean 0.3 cm H₂O, 95% CI ?0.8–1.4, P = 0.007] but did not vary with sleep stage (P = 0.91). This study has shown that the overall coefficient of repeatability was 4.1 cm H₂O, implying that the minimum detectable difference, with 95% probability, between two repeated Pcrit measurements in an individual is 4.1 cm H₂O. Such variability in overnight measures of Pcrit indicates that a single unqualified value of Pcrit cannot be used to characterize an individual’s overall collapsibility during sleep. When within‐subject variability is accounted for, change in body posture from supine to lateral significantly decreases passive pharyngeal collapsibility.