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.     

Posthypoxic ventilatory decline during NREM sleep: influence of sleep apnea.

We wished to determine the severity of posthypoxic ventilatory decline in patients with sleep apnea relative to normal subjects during sleep. We studied 11 men with sleep apnea/hypopnea syndrome and 11 normal men during non-rapid eye movement sleep. We measured EEG, electrooculogram, arterial O(2) saturation, and end-tidal P(CO2). To maintain upper airway patency in patients with sleep apnea, nasal continuous positive pressure was applied at a level sufficient to eliminate apneas and hypopneas. We compared the prehypoxic control (C) with posthypoxic recovery breaths. Nadir minute ventilation in normal subjects was 6.3 +/- 0.5 l/min (83.8 +/- 5.7% of room air control) vs. 6.7 +/- 0.9 l/min, 69.1 +/- 8.5% of room air control in obstructive sleep apnea (OSA) patients; nadir minute ventilation (% of control) was lower in patients with OSA relative to normal subjects (P < 0.05). Nadir tidal volume was 0.55 +/- 0.05 liter (80.0 +/- 6.6% of room air control) in OSA patients vs. 0.42 +/- 0.03 liter, 86.5 +/- 5.2% of room air control in normal subjects. In addition, prolongation of expiratory time (Te) occurred in the recovery period. There was a significant difference in Te prolongation between normal subjects (2.61 +/- 0.3 s, 120 +/- 11.2% of C) and OSA patients (5.6 +/- 1.5 s, 292 +/- 127.6% of C) (P < 0.006). In conclusion, 1) posthypoxic ventilatory decline occurred after termination of hypocapnic hypoxia in normal subjects and patients with sleep apnea and manifested as decreased tidal volume and prolongation of Te; and 2) posthypoxic ventilatory prolongation of Te was more pronounced in patients with sleep apnea relative to normal subjects.     

Respiratory timing during NREM sleep in patients with occlusive sleep apnea

To study respiratory timing mechanisms in patients with occlusive apnea, inspiratory and expiratory times (TI and TE) were calculated from the diaphragmatic electromyogram obtained in seven patients during non-rapid-eye-movement (NREM) sleep. Peak diaphragmatic activity (EMGdi) had a curvilinear relationship with TI during the ventilatory and occlusive phases such that TI shortened as EMGdi decreased during the ventilatory phase (r = 0.87, P less than 0.05) and it prolonged as EMGdi increased during the occlusive phase (r = 0.89, P less than 0.02). However, EMGdi vs. TI for the occlusive phase was shifted to the right of that for the ventilatory phase, reflecting the relatively longer TI during upper airway occlusion. TI also had a linear relationship with pleural pressure (r = 0.94, P less than 0.001) that remained unchanged during the ventilatory and occlusive phases such that it prolonged as negative inspiratory pressure increased. These results indicate that respiratory timing is continuously modified in patients with occlusive apnea as inspiratory neural drive fluctuates during NREM sleep and suggest that this modification is due to the net effects of changing inspiratory neural drive and afferent input predominantly from upper airway mechanoreceptors.     

Respiratory muscle interaction during NREM sleep in patients with occlusive apnea

To study respiratory muscle interaction in patients with occlusive apnea, diaphragmatic electromyogram (EMGdi) and gastric, pleural, and transdiaphragmatic pressures (Pga, Ppl, and Pdi, respectively) were studied in seven patients during non-rapid-eye-movement (NREM) sleep. Diaphragmatic force output, as assessed by Pdi, followed the periodic changes in EMGdi but during the occlusive phase the increase in Pdi was more than the increase in EMGdi. This increase in Pdi was essentially due to an increase in Ppl, since Pga and EMGdi had a linear relationship (r = 0.98, P less than 0.001) that did not change during the occlusive and ventilatory phases. Abdominal muscle recruitment evident in Pga and abdominal motion tracings during the occlusive phase when paradoxical rib cage motion was observed suggested that this increase in diaphragmatic efficiency was likely due to a change in diaphragmatic length-tension characteristics. These results demonstrate that, in patients with occlusive apneas, the diaphragm is the predominant respiratory muscle during NREM sleep and that its function is supported by abdominal muscle recruitment.     

Effect of testosterone on the apneic threshold in women during NREM sleep.

The hypocapnic apneic threshold (AT) is lower in women relative to men. To test the hypothesis that the gender difference in AT was due to testosterone, we determined the AT during non-rapid eye movement sleep in eight healthy, nonsnoring, premenopausal women before and after 10-12 days of transdermal testosterone. Hypocapnia was induced via nasal mechanical ventilation (MV) for 3 min with tidal volumes ranging from 175 to 215% above eupneic tidal volume and respiratory frequency matched to eupneic frequency. Cessation of MV resulted in hypocapnic central apnea or hypopnea depending on the magnitude of hypocapnia. Nadir minute ventilation as a percentage of control (%Ve) was plotted against the change in end-tidal CO(2) (Pet(CO(2))); %Ve was given a value of zero during central apnea. The AT was defined as the Pet(CO(2)) at which the apnea closest to the last hypopnea occurred; hypocapnic ventilatory response (HPVR) was defined as the slope of the linear regression Ve vs. Pet(CO(2)). Both the AT (39.5 +/- 2.9 vs. 42.1 +/- 3.0 Torr; P = 0.002) and HPVR (0.20 +/- 0.05 vs. 0.33 +/- 0.11%Ve/Torr; P = 0.016) increased with testosterone administration. We conclude that testosterone administration increases AT in premenopausal women, suggesting that the increased breathing instability during sleep in men is related to the presence of testosterone.     

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.     

Influence of age and gender on upper airway resistance in NREM and REM sleep.

The prevalence of irregular breathing during sleep is age and gender dependent, but the reason for this is unknown. This study tested the hypothesis that older men have a greater sleep-related increase in respiratory resistance. In 48 healthy subjects, 12 in each of four groups of younger and older men and women, airway resistance was measured during wakefulness and sleep using a mask, pneumotachograph, and catheter-mounted pressure sensors. Total respiratory resistance and total "low-flow," and "high-flow" oropharyngeal resistance were analyzed from 170,000 breaths, high flow being at rates above 50% maximal inspiratory flow. High-flow oropharyngeal and total respiratory resistance increased during non-rapid eye movement (NREM) sleep in all groups but not low-flow resistance. Total respiratory resistance increased from 12 +/- 1.2 cmH(2)O. l(-1). s(-1) awake to 16.2 +/- 2.4 in NREM sleep in young men, from 22.8 +/- 3.6 to 33.6 +/- 5.4 in young women, from 18 +/- 3 to 34.8 +/- 4.8 in older men, and from 26.6. +/- 4.2 to 34.2 +/- 6 in older women. The percentage of change in total respiratory resistance from awake to NREM sleep was not different between age groups or genders. We conclude that there are no major age or gender differences in the changes in airway resistance with sleep in normal subjects.     

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.     

Determinants of poststimulus potentiation in humans during NREM sleep.

To test whether active hyperventilation activates the "afterdischarge" mechanism during non-rapid-eye-movement (NREM) sleep, we investigated the effect of abrupt termination of active hypoxia-induced hyperventilation in normal subjects during NREM sleep. Hypoxia was induced for 15 s, 30 s, 1 min, and 5 min. The last two durations were studied under both isocapnic and hypocapnic conditions. Hypoxia was abruptly terminated with 100% inspiratory O2 fraction. Several room air-to-hyperoxia transitions were performed to establish a control period for hyperoxia after hypoxia transitions. Transient hyperoxia alone was associated with decreased expired ventilation (VE) to 90 +/- 7% of room air. Hyperoxic termination of 1 min of isocapnic hypoxia [end-tidal PO2 (PETO2) 63 +/- 3 Torr] was associated with VE persistently above the hyperoxic control for four to six breaths. In contrast, termination of 30 s or 1 min of hypocapnic hypoxia [PETO2 49 +/- 3 and 48 +/- 2 Torr, respectively; end-tidal PCO2 (PETCO2) decreased by 2.5 or 3.8 Torr, respectively] resulted in hypoventilation for 45 s and prolongation of expiratory duration (TE) for 18 s. Termination of 5 min of isocapnic hypoxia (PETO2 63 +/- 3 Torr) was associated with central apnea (longest TE 200% of room air); VE remained below the hyperoxic control for 49 s. Termination of 5 min of hypocapnic hypoxia (PETO2 64 +/- 4 Torr, PETCO2 decreased by 2.6 Torr) was also associated with central apnea (longest TE 500% of room air). VE remained below the hyperoxic control for 88 s. We conclude that 1) poststimulus hyperpnea occurs in NREM sleep as long as hypoxia is brief and arterial PCO2 is maintained, suggesting the activation of the afterdischarge mechanism; 2) transient hypocapnia overrides the potentiating effects of afterdischarge, resulting in hypoventilation; and 3) sustained hypoxia abolishes the potentiating effects of after-discharge, resulting in central apnea. These data suggest that the inhibitory effects of sustained hypoxia and hypocapnia may interact to cause periodic breathing.     

Effect of mechanical loading on expiratory and inspiratory muscle activity during NREM sleep

We investigated the effect of acute and sustained inspiratory resistive loading (IRL) on the activity of expiratory abdominal muscles (EMGab) and the diaphragm (EMGdi) and on ventilation during wakefulness and non-rapid-eye-movement (NREM) sleep in healthy subjects. EMGdi and EMGab were measured with esophageal and transcutaneous electrodes, respectively. During wakefulness, EMGdi increased in response to acute loading (18 cmH2O.l-1.s) (+23%); this was accompanied by preservation of tidal volume (VT) and minute ventilation (VE). During NREM sleep, no augmentation was noted in EMGdi or EMGab. Inspiratory time (TI) was prolonged (+5%), but this was not sufficient to prevent a decrease in both VT and VE (-21 and -20%, respectively). During sustained loading (12 cmH2O.l-1 s) in NREM sleep, control breaths (C) were compared with the steady-state loaded breaths (SS) defined by breaths 41-50. Steady-state IRL was associated with augmentation of EMGdi (12%) and EMGab (50%). VT returned to control levels, expiratory time shortened, and breathing frequency increased. The net result was the increase in VE above control levels (+5%, P less than 0.01). No change was noted in end-tidal CO2 or O2. We concluded that 1) wakefulness is a prerequisite for immediate load compensation (in its absence, TI prolongation is the only compensatory response) and 2) during sustained IRL, the augmentation of EMGdi and EMGab can lead to complete ventilatory recovery without measurable changes in chemical stimuli.     

Relationship between surface tension of upper airway lining liquid and upper airway collapsibility during sleep in obstructive sleep apnea hypopnea syndrome.

Lowering surface tension (gamma) of upper airway lining liquid (UAL) reduces upper airway opening (anesthetized humans) and closing (anesthetized rabbits) pressures. We now hypothesize that in sleeping obstructive sleep apnea hypopnea syndrome (OSAHS) patients lowering gamma of UAL will enhance upper airway stability and decrease the severity of sleep-disordered breathing. Nine OSAHS patients [respiratory disturbance index (RDI): 49 +/- 8 (SE) events/h, diagnostic night] participated in a two-part, one-night, polysomnography study. In the first part, upper airway closing pressures (during non-rapid eye movement sleep, Pcrit) were measured and samples of UAL (awake) were obtained before and after 2.5 ml of surfactant (Exosurf, Glaxo Smith Kline) was instilled into the posterior pharynx. The gamma of UAL was determined with the use of the "pull-off" force technique. In the second part, subjects received a second application of 2.5 ml of surfactant and then slept the remainder of the night (205 +/- 30 min). Instillation of surfactant decreased the gamma of UAL from 60.9 +/- 3.1 mN/m (control) to 45.2 +/- 2.5 mN/m (surfactant group) (n = 9, P < 0.001). Pcrit decreased from 1.19 +/- 1.14 cmH2O (control) to -0.56 +/- 1.15 cmH2O (surfactant group) (n = 7, P < 0.02). Compared with the second half of diagnostic night, surfactant decreased RDI from 51 +/- 8 to 35 +/- 8 events/h (n = 9, P < 0.03). The fall in RDI (deltaRDI) correlated with the fall in gamma of UAL (deltagamma) (deltaRDI = 1.8 x deltagamma, r = 0.68, P = 0.04). Hypopneas decreased approximately 50% from 42 +/- 8 to 20 +/- 5 events/h (n = 9, P < 0.03, paired t-test). The gamma of UAL measured the next morning remained low at 49.5 +/- 2.7 mN/m (n = 9, P < 0.001, ANOVA, compared with control). In conclusion, instillation of surfactant reduced the gamma of UAL in OSAHS patients and decreased Pcrit and the occurrence of hypopneas. Therapeutic manipulation of gamma of UAL may be beneficial in reducing the severity of sleep-disordered breathing in OSAHS patients.     

Effect of airway impedance on CO2 retention and respiratory muscle activity during NREM sleep

We hypothesized that a sleep-induced increase in mechanical impedance contributes to CO2 retention and respiratory muscle recruitment during non-rapid-eye-movement (NREM) sleep. The effect NREM sleep on respiratory muscle activity and CO2 retention was measured in healthy subjects who increased maximum total pulmonary resistance (RLmax, 1-81 cmH2O.l-1.s) from awake to NREM sleep. We determined the effects of this sleep-induced increase in airway impedance by steady-state inhalation of a reduced-density gas mixture (79% He-21% O2, He-O2). Both arterialized blood PCO2 (PaCO2) and end-tidal PCO2 (PETCO2) were measured. Inspiratory (EMGinsp) and expiratory (EMGexp) respiratory muscle electromyogram activity was measured. NREM sleep caused 1) RLmax to increase (7 +/- 3 vs. 39 +/- 28 cmH2O.l-1.s), 2) PaCO2 and/or PETCO2 to increase in all subjects (40 +/- 2 vs. 44 +/- 3 Torr), and 3) EMGinsp to increase in 8 of 9 subjects and EMGexp to increase in 9 of 17 subjects. Compared with steady-state air breathing during NREM sleep, steady-state He-O2 breathing 1) reduced RLmax by 38%, 2) decreased PaCO2 and PETCO2 by 2 Torr, and 3) decreased both EMGinsp (-20%) and EMGexp (-54%). We concluded that the sleep-induced increase in upper airway resistance accompanied by the absence of immediate load compensation is an important determinant of CO2 retention, which, in turn, may cause augmentation of inspiratory and expiratory muscle activity above waking levels during NREM sleep.     

阻塞性睡眠呼吸暂停低通气综合征患者血脂水平的变化

探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)与血脂水平的关系。方法:选取32例OSAHS患者(OSAHS组)为试验组和30例健康体检者为对照组,均经多导睡眠监测仪(PSG)检查,测定空腹血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)的含量,比较两组间的差异。结果:OSAHS组空腹时TC、TG、LDL显著高于对照组,而HDL显著低于对照组。结论:OSAHS可引起脂质代谢异常,从而促进心血管疾病的发生。     

Upper airway anesthesia delays arousal from airway occlusion induced during human NREM sleep.

Six healthy subjects (5 males and 1 female, 26-40 yr old) were studied during non-rapid-eye-movement (NREM) sleep to assess the role of upper airway (UA) afferents in the arousal response to induced airway occlusion. Subjects wore an airtight face mask attached to a low-resistance one-way valve. A valve in the inspiratory circuit allowed instantaneous inspiratory airway occlusion and release; the expiratory circuit remained unoccluded at all times. Each subject was studied during two nights. On one night, occlusions were created during stable stage 2 NREM sleep before and after application of 4% lidocaine to the oral and nasal mucosa. On the other night, the protocol was duplicated with saline ("sham anesthesia") rather than lidocaine. The order of nights was randomized. Occlusions were sustained until electroencephalographic arousal. Three to 12 occlusions were performed in each subject for each of the four parts of the protocol (pre- and post-lidocaine, pre- and post-saline). The auditory threshold for arousal (1,500-Hz tone beginning at 30 dB) was also tested before and after UA lidocaine. For the group, arousal time after UA anesthesia was prolonged compared with preanesthesia arousal time (P less than 0.001); arousal time after sham anesthesia did not significantly increase from before sham anesthesia (P = 0.9). The increase in arousal time with UA anesthesia was greater than the increase with sham anesthesia (P less than 0.001). The auditory arousal threshold did not increase after UA anesthesia. Inspiratory mask pressure, arterial O2 saturation of hemoglobin, and end-tidal PCO2 during occlusions were similar before and after UA anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Upper airway muscle responsiveness to rising PCO(2) during NREM sleep.

Although pharyngeal muscles respond robustly to increasing PCO(2) during wakefulness, the effect of hypercapnia on upper airway muscle activation during sleep has not been carefully assessed. This may be important, because it has been hypothesized that CO(2)-driven muscle activation may importantly stabilize the upper airway during stages 3 and 4 sleep. To test this hypothesis, we measured ventilation, airway resistance, genioglossus (GG) and tensor palatini (TP) electromyogram (EMG), plus end-tidal PCO(2) (PET(CO(2))) in 18 subjects during wakefulness, stage 2, and slow-wave sleep (SWS). Responses of ventilation and muscle EMG to administered CO(2) (PET(CO(2)) = 6 Torr above the eupneic level) were also assessed during SWS (n = 9) or stage 2 sleep (n = 7). PET(CO(2)) increased spontaneously by 0.8 +/- 0.1 Torr from stage 2 to SWS (from 43.3 +/- 0.6 to 44.1 +/- 0.5 Torr, P < 0.05), with no significant change in GG or TP EMG. Despite a significant increase in minute ventilation with induced hypercapnia (from 8.3 +/- 0.1 to 11.9 +/- 0.3 l/min in stage 2 and 8.6 +/- 0.4 to 12.7 +/- 0.4 l/min in SWS, P < 0.05 for both), there was no significant change in the GG or TP EMG. These data indicate that supraphysiological levels of PET(CO(2)) (50.4 +/- 1.6 Torr in stage 2, and 50.4 +/- 0.9 Torr in SWS) are not a major independent stimulus to pharyngeal dilator muscle activation during either SWS or stage 2 sleep. Thus hypercapnia-induced pharyngeal dilator muscle activation alone is unlikely to explain the paucity of sleep-disordered breathing events during SWS.     

Influence of arterial O2 on the susceptibility to posthyperventilation apnea during sleep.

To investigate the contribution of the peripheral chemoreceptors to the susceptibility to posthyperventilation apnea, we evaluated the time course and magnitude of hypocapnia required to produce apnea at different levels of peripheral chemoreceptor activation produced by exposure to three levels of inspired P(O2). We measured the apneic threshold and the apnea latency in nine normal sleeping subjects in response to augmented breaths during normoxia (room air), hypoxia (arterial O2 saturation = 78-80%), and hyperoxia (inspired O2 fraction = 50-52%). Pressure support mechanical ventilation in the assist mode was employed to introduce a single or multiple numbers of consecutive, sigh-like breaths to cause apnea. The apnea latency was measured from the end inspiration of the first augmented breath to the onset of apnea. It was 12.2 +/- 1.1 s during normoxia, which was similar to the lung-to-ear circulation delay of 11.7 s in these subjects. Hypoxia shortened the apnea latency (6.3 +/- 0.8 s; P < 0.05), whereas hyperoxia prolonged it (71.5 +/- 13.8 s; P < 0.01). The apneic threshold end-tidal P(CO2) (Pet(CO2)) was defined as the Pet(CO2)) at the onset of apnea. During hypoxia, the apneic threshold Pet(CO2) was higher (38.9 +/- 1.7 Torr; P < 0.01) compared with normoxia (35.8 +/- 1.1; Torr); during hyperoxia, it was lower (33.0 +/- 0.8 Torr; P < 0.05). Furthermore, the difference between the eupneic Pet(CO2) and apneic threshold Pet(CO2) was smaller during hypoxia (3.0 +/- 1.0 Torr P < 001) and greater during hyperoxia (10.6 +/- 0.8 Torr; P < 0.05) compared with normoxia (8.0 +/- 0.6 Torr). Correspondingly, the hypocapnic ventilatory response to CO2 below the eupneic Pet(CO2) was increased by hypoxia (3.44 +/- 0.63 l.min(-1).Torr(-1); P < 0.05) and decreased by hyperoxia (0.63 +/- 0.04 l.min(-1).Torr(-1); P < 0.05) compared with normoxia (0.79 +/- 0.05 l.min(-1).Torr(-1)). These findings indicate that posthyperventilation apnea is initiated by the peripheral chemoreceptors and that the varying susceptibility to apnea during hypoxia vs. hyperoxia is influenced by the relative activity of these receptors.     

Gender differences in upper airway compliance during NREM sleep: role of neck circumference.

It has been proposed that the gender difference in sleep apnea prevalence is related to gender differences in upper airway structure and function. We hypothesized that men would have smaller retropalatal cross-sectional area and higher compliance during sleep compared with women. Using upper airway imaging, we measured upper airway cross-sectional area and retropalatal compliance in wakefulness and non-rapid eye movement (NREM) sleep in 15 men and 15 women without sleep-disordered breathing. Cross-sectional area at the beginning of inspiration tended to be larger in men compared with women in both wakefulness [194.5 +/- 21.3 vs. 138.8 +/- 12.0 (SE) mm(2)] and NREM sleep (111.1 +/- 17.6 vs. 83.3 +/- 11.9 mm(2); P = 0.058). There was no significant difference, however, after correction for body surface area. Retropalatal compliance also tended to be higher in men during both wakefulness (5.9 +/- 1.4 vs. 3.1 +/- 1.4 mm(2)/cmH(2)O; P = 0.006) and NREM sleep (12.6 +/- 2.7 vs. 4.7 +/- 2.6 mm(2)/cmH(2)O; P = 0.055). However, compliance was similar in men relative to women after correction for neck circumference. We conclude that the gender difference in retropalatal compliance is more accurately attributed to differences in neck circumference between the genders.