Sleep-dependent changes in the coupling between heart period and blood pressure in human subjects

We investigated whether in human subjects, the pattern of coupling between the spontaneous fluctuations of heart period (HP) and those of systolic blood pressure (SBP) differs among wake-sleep states. Polysomnographic recordings and finger blood pressure measurements were performed for 48 h in 15 nonobese adults without sleep-disordered breathing. The cross-correlation function (CCF) between the fluctuations of HP and SBP at frequencies <0.15 Hz was computed during quiet wakefulness (QW), light (stages 1 and 2) and deep (stages 3 and 4) nonrapid-eye-movement sleep (NREMS), and rapid-eye-movement sleep (REMS). A positive correlation between HP and the previous SBP values, which is the expected result of baroreflex feedback control, was observed in the sleep states but not in QW. In deep NREMS, the maximum CCF value was significantly higher than in any other state, suggesting the greatest baroreflex contribution to the coupling between HP and SBP. A negative correlation between HP and the subsequent SBP values was also observed in each state, consistent with the mechanical feed-forward action of HP on SBP and with central autonomic commands. The contribution of these mechanisms to the coupling between HP and SBP, estimated from the minimum CCF value, was significantly lower in deep NREMS than either in light NREMS or QW. These results indicate that the pattern of coupling between HP and SBP at low frequencies differs among wake-sleep states in human subjects, with deep NREMS entailing the highest feedback contribution of the baroreflex and a low effectiveness of feed-forward mechanisms.     

Identification of respiratory vagal feedback in awake normal subjects using pseudorandom unloading.

Evidence of the Hering-Breuer reflex has been found in humans during anesthesia and sleep but not during wakefulness. Cortical influences, present during wakefulness, may mask the effects of this reflex in awake humans. We hypothesized that, if lung volume were increased in awake subjects unaware of the stimulus, vagal feedback would modulate breathing on a breath-to-breath basis. To test this hypothesis, we employed proportional assist ventilation in a pseudorandom sequence to unload the respiratory system above and below the perceptual threshold in 17 normal subjects. Tidal volume, integrated respiratory muscle pressure per breath, and inspiratory time were recorded. Both sub- and suprathreshold stimulation evoked a significant increase in tidal volume and inspiratory flow rate, but a significant decrease in inspiratory time was present only during the application of a subthreshold stimulus. We conclude that vagal feedback modulates respiratory timing on a breath-by-breath basis in awake humans, as long as there is no awareness of the stimulus.     

Possible mechanisms of periodic breathing during sleep

To determine the effect of respiratory control system loop gain on periodic breathing during sleep, 10 volunteers were studied during stage 1-2 non-rapid-eye-movement (NREM) sleep while breathing room air (room air control), while hypoxic (hypoxia control), and while wearing a tight-fitting mask that augmented control system gain by mechanically increasing the effect of ventilation on arterial O2 saturation (SaO2) (hypoxia increased gain). Ventilatory responses to progressive hypoxia at two steady-state end-tidal PCO2 levels and to progressive hypercapnia at two levels of oxygenation were measured during wakefulness as indexes of controller gain. Under increased gain conditions, five male subjects developed periodic breathing with recurrent cycles of hyperventilation and apnea; the remaining subjects had nonperiodic patterns of hyperventilation. Periodic breathers had greater ventilatory response slopes to hypercapnia under either hyperoxic or hypoxic conditions than nonperiodic breathers (2.98 +/- 0.72 vs. 1.50 +/- 0.39 l.min-1.Torr-1; 4.39 +/- 2.05 vs. 1.72 +/- 0.86 l.min-1.Torr-1; for both, P less than 0.04) and greater ventilatory responsiveness to hypoxia at a PCO2 of 46.5 Torr (2.07 +/- 0.91 vs. 0.87 +/- 0.38 l.min-1.% fall in SaO2(-1); P less than 0.04). To assess whether spontaneous oscillations in ventilation contributed to periodic breathing, power spectrum analysis was used to detect significant cyclic patterns in ventilation during NREM sleep. Oscillations occurred more frequently in periodic breathers, and hypercapnic responses were higher in subjects with oscillations than those without. The results suggest that spontaneous oscillations in ventilation are common during sleep and can be converted to periodic breathing with apnea when loop gain is increased.     

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.     

Isoprene and sleep

Isoprene is one of the main constituents of endogenous origin in exhaled human breath. The concentration of isoprene seems to vary with states of sleep and wakefulness, increasing during sleep and decreasing sharply just after awakening. Thus, isoprene may be involved in in sleep upholding.     

正常人和无睡眠呼吸异常慢病患者睡眠期间的呼吸源性心率变异初步报告*

目的: 整体整合生理学医学新理论-呼吸循环代谢等系统一体化调控提出了呼吸为循环指标变异性起源的假说,我们对人睡眠期间的呼吸和心率变异分别分析,探索心率变异的起源。方法: 本研究回顾性分析了2014年以来行心肺运动试验（CPET）、多导睡眠图（PSG）鼻气流和心电图监测的8例无疾病诊断的正常人和10例无睡眠呼吸异常的慢性疾病患者,分析夜晚睡眠期间鼻气流的呼吸周期与心电图R-R间期心率变异周期的关系。一个完整的呼吸周期包括吸气过程和紧接着的呼气过程,分析计算呼吸周期数、平均呼吸周期时间等指标。心率由心电图的R-R间期计算获得,连续一次心率由最低点上升至最高点,再由最高点下降至最低点,为一个心率变异周期,计算心率变异周期数、平均心率变异时间、心率变异平均幅度等指标。比较同一人呼吸和心率变异指标之间的相互关系,以及两组人群之间的异同。结果: 正常人峰值摄氧量、无氧阈等CPET核心指标均显著优于无睡眠呼吸异常的慢性疾病患者（P<0.05）。正常人AHI（（1.7±1.3）次/小时）和无睡眠呼吸异常慢性疾病患者AHI（（2.9±1.2）次/小时）无差异（P>0.05）。正常人呼吸周期数与心率变异周期数（（6581.63±1411.90）次、（6638.38±1459.46）次）、平均呼吸周期时间与平均心率变异周期时间（（4.19±0.57）s、（4.16±0.62）s）均高度一致,无差异（P>0.05）。无睡眠呼吸异常的慢性疾病患者上述指标比较（（7354.50±1443.50）次与（7291.20±1399.31）次、（4.20±0.69）s与（4.23±0.68）s）也是高度一致,无统计学差异（P>0.05）。正常人呼吸周期数/心率变异周期数（0.993±0.027）与无睡眠呼吸异常的慢性疾病患者呼吸周期数/心率变异周期数（1.008±0.024）比值均接近1。正常人心率变化平均幅度（（5.74±3.21） bpm）略高于无睡眠呼吸异常的慢性疾病患者（（2.88±1.44） bpm,P<0.05）。结论: 正常人和无睡眠呼吸异常的慢性疾病患者无论功能状态如何,心率变异与呼吸存在极其相似的一致性,其心率变异的始发因素均为呼吸所致。     

Inhibition of heart rate variability during sleep in humans by 6700 K pre-sleep light exposure

Two different spectral analyses of heart rate (HR) variability (HRV) were performed on seven young male subjects to evaluate the effects of different color temperatures of light exposure (6700 K, 5000 K, 3000 K) before sleep on cardiac vagal activity. In investigating HRV, we used an ordinary fast Fourier transform (FFT) and coarse graining spectral analysis (CGSA), which selectively extracts random fractal components from a given time series. The results showed that suppressions of HR during sleep after 6700 K light exposure were more inhibited than the other two lighting conditions. Increases in high-frequency (HF) components of HRV during sleep were also inhibited by 6700 K pre-sleep lighting. These results indicate that pre-sleep exposure to light of a higher color temperature may inhibit the enhancement of cardiac vagal activity during sleep. Moreover, significant HF alterations were shown in fractal-free HF (not in ordinary HF) components by CGSA. Because the HF component originates from respiratory sinus arrhythmia with periodical fluctuations, CGSA may be an appropriate approach for HRV evaluation during sleep.     

Midlatency auditory evoked responses: Differential effects of sleep in the human

Middle latency responses (MLRs) in the 10–100 msec latency range, evoked by click stimuli, were studied in 14 adult volunteer subjects during sleep-wakefulness to determine whether such changes in state were reflected by any MLR component. Evoked potentials were collected in 500 trial averages during continuos presentation of 1/sec clicks during initial awake recordings and thereafter during a 2 h afternoon nap or all-night sleep session. Continuously recorded EEG, EOG and EMG were scored for wakefulness, stages 2–4 of slow wave sleep (SWS), and rapid eye movement (REM) sleep during each evoked potential epoch. The major components included in this study and their latency ranges, as determined by peak latency measurements from the awake records, were: ABR V, 5–8 msec, Pa, 30–40 msec, Nb, 45–55 msec, and P1, 55–80 msec. In agreement with previous reports, ABR V and Pa showed no amplitude changes from wakefulness to either SWS or REM. Not previously reported, however, was the dramatic decrease and disappearance of P1 during SWS and its reappearance during REM to an amplitude similar to that during wakefulness. This unique linkage between a particular evoked potential component and sleep-wakefulness indicates that its generator system must be functionally related to states of arousal. Relevant data from the cat model suggest that the generator substrate for P1 may be within the ascending reticular activating system.     

Vagal feedback in the entrainment of respiration to mechanical ventilation in sleeping humans.

We studied the capacity of four "normal" and six lung transplant subjects to entrain neural respiratory activity to mechanical ventilation. Two transplant subjects were studied during wakefulness and demonstrated entrainment indistinguishable from that of normal awake subjects. We studied four normal subjects and four lung transplant subjects during non-rapid eye movement (NREM) sleep. Normal subjects entrained to mechanical ventilation over a range of ventilator frequencies that were within +/-3-5 breaths of the spontaneous respiratory rate of each subject. After lung transplantation, during which the vagi were cut, subjects did demonstrate entrainment during NREM sleep; however, entrainment only occurred at ventilator frequencies at or above each subject's spontaneous respiratory rate, and entrainment was less effective. We conclude that there is no absolute requirement for vagal feedback to induce entrainment in subjects, which is in striking contrast to anesthetized animals in which vagotomy uniformly abolishes entrainment. On the other hand, vagal feedback clearly enhances the fidelity of entrainment and extends the range of mechanical frequencies over which entrainment can occur.     

Effect of sleep restriction on orthostatic cardiovascular control in humans.

We hypothesized that sleep restriction (4 consecutive nights, 4 h sleep/night) attenuates orthostatic tolerance. The effect of sleep restriction on cardiovascular responses to simulated orthostasis, arterial baroreflex gain, and heart rate variability was evaluated in 10 healthy volunteers. Arterial baroreflex gain was determined from heart rate responses to nitroprusside-phenylephrine injections, and orthostatic tolerance was tested via lower body negative pressure (LBNP). A Finapres device measured finger arterial pressure. No difference in baroreflex function, heart rate variability, or LBNP tolerance was observed with sleep restriction (P > 0.3). Systolic pressure was greater at -60 mmHg LBNP after sleep restriction than before sleep restriction (110 +/- 6 and 124 +/- 3 mmHg before and after sleep restriction, respectively, P = 0.038), whereas heart rate decreased (108 +/- 8 and 99 +/- 8 beats/min before and after sleep restriction, respectively, P = 0.028). These data demonstrate that sleep restriction produces subtle changes in cardiovascular responses to simulated orthostasis, but these changes do not compromise orthostatic tolerance.     

Cascade model of ventricular-arterial coupling and arterial-cardiac baroreflex function for cardiovascular variability in humans

Cardiovascular variability reflects autonomic regulation of blood pressure (BP) and heart rate (HR). However, systolic BP (SBP) variability also may be induced by fluctuations in stroke volume through left ventricular end-diastolic pressure (LVEDP) variability via dynamic ventricular-arterial coupling during respiration. We hypothesized that dynamic ventricular-arterial coupling is modulated by changes in left ventricular compliance associated with altered preload and that a cascade control mechanism of ventricular-arterial coupling with arterial-cardiac baroreflex function contributes to the genesis of cardiovascular variability at the respiratory frequency. Seven healthy young subjects underwent 6-min recordings of beat-by-beat LVEDP, SBP, and HR in the supine position with controlled respiration at 0.2 Hz during hyper- and hypovolemia. Spectral and transfer function analysis of these variables was conducted between 0.18 and 0.22 Hz. Dynamic ventricular-arterial coupling gain (Gain LVEDP-SBP) was smaller by 25% (P = 0.009) during hypervolemia than during hypovolemia, whereas arterial-cardiac baroreflex function gain (Gain SBP-HR) was similar. As predicted from a cascade model, a linear relationship between Gain LVEDP-HR and LVEDP-SBP times Gain SBP-HR was identified (R(2) = 0.93, P < 0.001). Gain LVEDP-HR was smaller by 40% (P = 0.04) during hypervolemia than during hypovolemia, leading to a reduction in spectral power of HR variability by 45% (P = 0.08). We conclude that dynamic ventricular-arterial coupling gain is reduced during hypervolemia because of a decrease in left ventricular compliance. A cascade model of ventricular-arterial coupling with the arterial-cardiac baroreflex contributes to the genesis of cardiovascular variability at the respiratory frequency.     

The link between cardiac autonomic activity and sleep delta power is altered in men with sleep apnea-hypopnea syndrome

We hypothesize that sleep apnea-hypopnea alters interaction between cardiac vagal modulation and sleep delta EEG. Sleep apnea-hypopnea syndrome (SAHS) is related to cardiovascular complications in men. SAHS patients show higher sympathetic activity than normal subjects. In healthy men, non-rapid eye movement (NREM) sleep is associated with cardiac vagal influence, whereas rapid eye movement (REM) sleep is linked to cardiac sympathetic activity. Interaction between cardiac autonomic modulation and delta sleep EEG is not altered across a life span nor is the delay between appearances of modifications in both signals. Healthy controls, moderate SAHS, and severe SAHS patients were compared across the first three NREM-REM cycles. Spectral analysis was applied to ECG and EEG signals. High frequency (HF) and low frequency (LF) of heart rate variability (HRV), ratio of LF/HF, and normalized (nu) delta power were obtained. A coherency analysis between HF(nu) and delta was performed, as well as a correlation analysis between obstructive apnea index (AI) or hypopnea index (HI) and gain, coherence, or phase shift. HRV components were similar between groups. In each group, HF(nu) was larger during NREM, while LF(nu) predominated across REM and wake stages. Coherence and gain between HF(nu) and delta decreased from controls to severe SAHS patients. In SAHS patients, the delay between modifications in HF(nu) and delta did not differ from zero. AI and HI correlated negatively with coherence, while HI correlated negatively with gain only. Apneas-hypopneas affect the link between cardiac sympathetic and vagal modulation and delta EEG demonstrated by the loss of cardiac autonomic activity fluctuations across shifts in sleep stages. Obstructive apneas and hypopneas alter the interaction between both signals differently.     

Effects of sleep pressure on endogenous cardiac autonomic activity and body temperature.

This study investigated the effects of variations in sleep pressure on cardiac autonomic activity and body temperature. In a counterbalanced design, 12 healthy, young subjects (6 men and 6 women) remained recumbent during 30 h of wakefulness (high sleep pressure) and 6 h of wakefulness (low sleep pressure). Both periods of wakefulness were immediately followed by a sleep opportunity, and the first 2 h of sleep were analyzed. During extended hours of wakefulness, a reduction in heart rate was mediated by a decline in cardiac sympathetic activity (measured via preejection period) and the maintenance of cardiac parasympathetic activity (measured via respiratory sinus arrhythmia). In subsequent high-pressure sleep, parasympathetic activity was amplified and sympathetic activity was negatively associated with electroencephalographic slow-wave activity. Sleep deprivation had no impact on foot temperature, but it did alter the pattern of change in core body temperature. A downregulation of cardiac autonomic activity during both extended hours of wakefulness and subsequent sleep may respectively provide "protection" and "recovery" from the temporal extension of cardiac demand.     

Sympathetic neural responses to 24-hour sleep deprivation in humans: sex differences

Sleep deprivation has been linked to hypertension, and recent evidence suggests that associations between short sleep duration and hypertension are stronger in women. In the present study we hypothesized that 24 h of total sleep deprivation (TSD) would elicit an augmented pressor and sympathetic neural response in women compared with men. Resting heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) were measured in 30 healthy subjects (age, 22 ± 1; 15 men and 15 women). Relations between spontaneous fluctuations of diastolic arterial pressure and MSNA were used to assess sympathetic baroreflex function. Subjects were studied twice, once after normal sleep and once after TSD (randomized, crossover design). TSD elicited similar increases in systolic, diastolic, and mean BP in men and women (time, P < 0.05; time × sex, P > 0.05). TSD reduced MSNA in men (25 ± 2 to 16 ± 3 bursts/100 heart beats; P = 0.02), but not women. TSD did not alter spontaneous sympathetic or cardiovagal baroreflex sensitivities in either sex. However, TSD shifted the spontaneous sympathetic baroreflex operating point downward and rightward in men only. TSD reduced testosterone in men, and these changes were correlated to changes in resting MSNA (r = 0.59; P = 0.04). Resting HR, respiratory rate, and estradiol were not altered by TSD in either sex. In conclusion, TSD-induced hypertension occurs in both sexes, but only men demonstrate altered resting MSNA. The sex differences in MSNA are associated with sex differences in sympathetic baroreflex function (i.e., operating point) and testosterone. These findings may help explain why associations between sleep deprivation and hypertension appear to be sex dependent.     

Alteration of cardiovascular autonomic functions by vegetarian diets in postmenopausal women is related to LDL cholesterol levels

This study was designed to test the hypothesis that alteration of cardiovascular autonomic functions by vegetarian diets in healthy postmenopausal women is related to lipid metabolism. A total of 70 healthy postmenopausal women not on hormone therapy participated in this study: 35 were vegetarians (mean age 55.0 years) and 35 were omnivores (mean age 55.1 years). Cardiovascular autonomic functions and baroreflex sensitivity were evaluated by specific frequency-domain measures of heart rate variability (HRV) and arterial blood pressure fluctuation. The vegetarians had statistically significant lowered blood pressure, total cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride, and fasting glucose levels compared with the omnivores. The vegetarians exhibited a significant higher total power, low-frequency (LF; 0.04-0.15 Hz) and high-frequency (HF; 0.15-0.4 Hz) of HRV and increased baroreflex sensitivity measures [Brr(LF) and Brr(HF)] compared with the omnivores. Total power, LF and HF of HRV, Brr(LF), and Brr(HF) were significantly and negatively correlated with LDL-cholesterol concentrations (P < 0.01). We concluded that the increases of cardiac vagal activity and baroreflex sensitivity by vegetarian diets in postmenopausal women are inversely related to LDL-cholesterol levels.     

Intraindividual validation of heart rate variability indexes to measure vagal effects on hearts

Heart rate variability (HRV) has been widely used as a measure of vagal activation in physiological, psychological, and clinical examinations. We studied the within-subject quantitative relationship between HRV and vagal effects on the heart in different body postures during a gradually decreasing vagal blockade. Electrocardiogram and respiratory frequency were measured in subjects (8 endurance athletes and 10 participants of nonendurance sports) in supine, sitting, and standing postures before the blockade, under vagal blockade (atropine sulfate, 0.04 mg/kg), and four times during a 150-min recovery from the blockade. Fast Fourier transform was used to calculate low-frequency power (LFP, 0.04-0.15 Hz), high-frequency power (HFP, 0.15-0.40 Hz), and total power (TP, 0.04-0.40 Hz). A within-subject linear regression analysis of recovery time on each HRV index was conducted. Complete vagal blockade decreased all HRV significantly, particularly HFP (P < 0.001). A linear fit explained a large portion of the within-subject variance between recovery time and natural log-transformed (ln) HRV indexes in every posture, with coefficients of determination (R2) in the supine posture [means (SD)]: 98 (SD 2)% for mean R-R interval, 87 (SD 10)% for lnLFP, 87 (SD 13)% for lnHFP, and 91 (SD 10)% for lnTP. Neither body posture nor endurance-training background had an impact on R2 values. There was marked between-subject variation in the R2 values, slopes, and intercepts. In conclusion, all HRV, particularly HFP, is predominantly under vagal control. Within subjects, lnLFP, lnHFP, and lnTP increased linearly with the gradually decreasing vagal blockade in all postures.     

Baroreflexes of the rat. III. Open-loop gain and electroencephalographic arousal

In early studies of humans, baroreflex sensitivity was found to be higher during sleep; however, subsequent observations in several species, including humans, have been at variance with the original reports. Sleep and arousal are behavioral states, and it is difficult to accurately and repeatedly measure baroreflex sensitivity in behaving animals. However, pharmacologically immobilized (neuromuscularly blocked) rats have apparently normal sleep-wakefulness cycles, and baroreflex gain can be measured directly in this preparation. Using the delta band of the EEG (EEG(delta)) as an index of sleep and arousal and open-loop aortic depressor nerve (ADN) stimulation as a baroreflex input, we found that blood pressure (BP) level depended on arousal (r = -0.416; P < 0.0001), and BP baroreflex gain depended on BP level (r = 0.496; P < 0.0001), but that BP baroreflex gain was independent of arousal (r = 0.001; NS). Heart period (HP) was different; although HP level depended on arousal (r = 0.352; P < 0.0001), HP baroreflex gain did not depend on HP level (r = 0.029; NS), and HP baroreflex gain increased with arousal (r = 0.315; P < 0.0001). A partial-correlations analysis showed that the presence of the relationship between BP level and BP baroreflex gain probably attenuated the relationship between arousal and BP gain. The results are consistent 1) with physiological findings showing that arousal attenuates afferent transmission through the nucleus of the solitary tract and enhances sympathoinhibition at the rostral ventrolateral medulla; and 2) with observations in humans and animals showing increased cardiac baroreflex sensitivity during sleep, but little if any effect of sleep on BP baroreflex sensitivity. The findings are relevant to all methods of baroreflex gain estimation that use HP as the index of baroreflex activation.     

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.     

Response to inspiratory resistive loading during sleep in normal children and children with obstructive apnea.

The response to inspiratory resistance loading (IRL) of the upper airway during sleep in children is not known. We, therefore, evaluated the arousal responses to IRL during sleep in children with the obstructive sleep apnea syndrome (OSAS) compared with controls. Children with OSAS aroused at a higher load than did controls (23 +/- 8 vs. 15 +/- 7 cmH(2)O. l(-1). s; P < 0.05). Patients with OSAS had higher arousal thresholds during rapid eye movement (REM) vs. non-REM sleep (P < 0.001), whereas normal subjects had lower arousal thresholds during REM (P < 0.005). Ventilatory responses to IRL were evaluated in the controls. There was a marked decrease in tidal volume both immediately (56 +/- 17% of baseline at an IRL of 15 cmH(2)O. l(-1). min; P < 0.001) and after 3 min of IRL (67 +/- 23%, P < 0.005). The duty cycle increased. We conclude that children with OSAS have impaired arousal responses to IRL. Despite compensatory changes in respiratory timing, normal children have a decrease in minute ventilation in response to IRL during sleep. However, arousal occurs before gas-exchange abnormalities.     

Decreased fractal component of human heart rate variability during non-REM sleep

The physiological significance of the fractal component of short-term, spontaneous heart rate variability (HRV) in humans remains unclear. The aim of the present study was to gain further information about the respective fractal components by extracting them from HRV, blood pressure variability (BPV), and instantaneous lung volume (ILV) time series via coarse graining spectral analysis in nine healthy subjects during waking and sleep states. The results show that the contribution made by the fractal component to the total variance in the beat-to-beat R-R interval declined significantly as the depth of non-rapid eye movement (non-REM) sleep increased, that the ILV time series was largely periodic (i.e., nonfractal), and that BPV was unaffected by sleep stage. Finally, the fractal component of HRV during REM sleep was found to be quite similar to that seen during waking. These results suggest that mechanisms involving electroencephalographic desynchronization and/or conscious states of the brain are reflected in the fractal component of HRV.