Occlusion pressure and ventilation during sleep in normal humans

Previous investigation in normal humans has demonstrated reduced ventilation and ventilatory responses to chemical stimuli during sleep. Most have interpreted this to be a product of decreasing central nervous system sensitivity to the normal stimuli that maintain ventilation, whereas other factors such as increasing airflow resistance could also contribute to this reduction in respiration. To improve our understanding of these events, we measured ventilation and occlusion pressures (P0.1) during unstimulated ventilation and rebreathing-induced hypercapnia during wakefulness and non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep. Eighteen subjects (10 males and 8 females) of whom seven were snorers (5 males and 2 females) were studied. Ventilation was reduced during both NREM and REM sleep (P less than 0.05), but this decrement in minute ventilation tended to be greater in snorers than nonsnorers. Unstimulated P0.1, on the other hand, was maintained or increased during sleep in all groups studied, with males and snorers showing the largest increase. The hypercapnic ventilatory response fell during both NREM and REM sleep and tended to be lower during REM than NREM sleep. However, the P0.1 response to hypercapnia during NREM sleep was well maintained at the waking level although the REM response was statistically reduced. These studies suggest that the mechanism of the reduction in ventilation and the hypercapnic ventilatory response seen during sleep, particularly NREM sleep, is likely to be multifactorial and not totally a product of decreasing central respiratory drive.     

Effects of sleep deprivation on respiratory events during sleep in healthy infants

This study was designed to determine the effects of sleep deprivation on respiratory events during sleep in healthy infants. Ten unsedated full-term infants (1-6 mo) were monitored polygraphically during "afternoon naps" on a control day and on the day after sleep deprivation. Respiratory events, i.e., central apnea, obstructive apnea and hypopnea, and periodic breathing were tabulated. Results for respiratory events were expressed as 1) indexes of the total number of respiratory events and of specific respiratory events per hour of total sleep (TST), "quiet" sleep (QS) and "active" sleep (AS) times; 2) total duration of total and specific respiratory events, expressed as a percentage of TST, QS, and AS times. After sleep deprivation, significant increases were observed for 1) respiratory event (P less than 0.001), central apnea (P less than 0.05), and obstructive respiratory event (P less than 0.01) indexes; 2) respiratory event time as a percentage of TST (P less than 0.002) and as a percentage of AS time (P less than 0.001); 3) obstructive respiratory event time as a percentage of TST (P less than 0.01), QS (P less than 0.05), and AS times (P less than 0.002). The present study shows that short-term sleep deprivation in healthy infants increases the number and timing of respiratory events, especially obstructive events in AS.     

Selective REM sleep deprivation during daytime I. Time course of interventions and recovery sleep

Although repeated selective rapid eye movement (REM) sleep deprivation by awakenings during nighttime has shown that the number of sleep interruptions required to prevent REM sleep increases within and across consecutive nights, the underlying regulatory processes remained unspecified. To assess the role of circadian and homeostatic factors in REM sleep regulation, REM sleep was selectively deprived in healthy young adult males during a daytime sleep episode (7-15 h) after a night without sleep. Circadian REM sleep propensity is known to be high in the early morning. The number of interventions required to prevent REM sleep increased from the first to the third 2-h interval by a factor of two and then leveled off. Only a minor REM sleep rebound (11.6%) occurred in the following undisturbed recovery night. It is concluded that the limited rise of interventions during selective daytime REM sleep deprivation may be due to the declining circadian REM sleep propensity, which may partly offset the homeostatic drive and the sleep-dependent disinhibition of REM sleep.     

Increased sympathetic and decreased parasympathetic cardiovascular modulation in normal humans with acute sleep deprivation.

Cardiovascular autonomic modulation during 36 h of total sleep deprivation (SD) was assessed in 18 normal subjects (16 men, 2 women, 26.0 +/- 4.6 yr old). ECG and continuous blood pressure (BP) from radial artery tonometry were obtained at 2100 on the first study night (baseline) and every subsequent 12 h of SD. Each measurement period included resting supine, seated, and seated performing computerized tasks and measured vigilance and executive function. Subjects were not supine in the periods between measurements. Spectral analysis of heart rate variability (HRV) and BP variability (BPV) was computed for cardiac parasympathetic modulation [high-frequency power (HF)], sympathetic modulation [low-frequency power (LF)], sympathovagal balance (LF/HF power of R-R variability), and BPV sympathetic modulation (at LF). All spectral data were expressed in normalized units [(total power of the components/total power-very LF) x 100]. Spontaneous baroreflex sensitivity (BRS), based on systolic BP and pulse interval powers, was also measured. Supine and sitting, BPV LF was significantly increased from baseline at 12, 24, and 36 h of SD. Sitting, HRV LF was increased at 12 and 24 h of SD, HRV HF was decreased at 12 h SD, and HRV LF/HF power of R-R variability was increased at 12 h of SD. BRS was decreased at 24 h of SD supine and seated. During the simple reaction time task (vigilance testing), the significantly increased sympathetic and decreased parasympathetic cardiac modulation and BRS extended through 36 h of SD. In summary, acute SD was associated with increased sympathetic and decreased parasympathetic cardiovascular modulation and decreased BRS, most consistently in the seated position and during simple reaction-time testing.     

Ventilation during early and late rapid-eye-movement sleep in normal humans.

Because successive rapid-eye-movement (REM) sleep periods in the night are longer in duration and have more phasic events, ventilation during late REM sleep might be more affected than in earlier episodes. Despite the increase in eye movement density (EMD) in late REM sleep, average minute ventilation was, however, not reduced compared with that in early REM sleep. Decreases in rib cage motion (mean inspiratory flow of the rib cage) in association with increasing EMD were offset by increments in respiratory frequency. Apart from expiratory time, there were no significant changes in the slopes of the relationships between EMD and specific ventilatory components, from early to late REM sleep periods. However, there was an increase in the number of episodes when ventilation was reduced during late REM sleep. Changes in ventilatory pattern during late REM sleep are due to changes in the underlying nature of REM sleep. The ventilatory response during eye movements is, however, subject specific. Some subjects exhibit large decrements in mean inspiratory flow of the rib cage and increments in respiratory frequency during bursts of eye movement, whereas other individuals demonstrate only small changes in these ventilatory parameters.     

Metabolism during normal, fragmented, and recovery sleep.

Average metabolic data (O2 uptake and CO2 output) were obtained for each 3-min period during consecutive nights of normal, experimentally fragmented, and recovery sleep in a group of 12 normal young adult males. Naturally occurring arousals and awakenings resulted in a characteristic increase in metabolism on the baseline night. The placement of brief frequent experimental arousals on the following night resulted in significantly increased metabolism throughout the night and significantly decreased sleep restoration as measured by morning performance, mood, and alertness tests, even though total sleep time was minimally reduced. Metabolic variables were significantly decreased compared with baseline on the nondisturbed recovery night that followed the sleep fragmentation night. The data cannot be used to infer that increased metabolism during sleep causes nonrestorative sleep, but the direction and time course of metabolic change accompanying arousal are consistent with that hypothesis.     

Effects of haloperidol on ventilation during isocapnic hypoxia in humans

Pedersen, Michala E. F., Keith L. Dorrington, and Peter A. Robbins. Effects of haloperidol on ventilation during isocapnic hypoxia in humans. J. Appl. Physiol.83(4): 1110-1115, 1997.Exposure to isocapnic hypoxia produces anabrupt increase in ventilation [acute hypoxic ventilatoryresponse (AHVR)], which is followed by a subsequent decline[hypoxic ventilatory depression or decline (HVD)]. In cats, both anesthetized and awake,haloperidol has been reported to increase AHVR and almost entirelyabolish HVD. To investigate whether this occurs in humans, theventilatory responses of 15 healthy young volunteers to 20 min ofisocapnic hypoxia (end-tidal PO₂ = 50 Torr) were assessed at 1, 2, and 4.5 h after placebo (control) andafter oral haloperidol (Seranace, 0.05 mg/kg) on different days. Threesubjects were unable to complete the study because of akathisia. AHVRwas significantly greater with haloperidol compared with control(P < 0.01, analysis of variance).However, no significant change in HVD was found [control HVD = 9.3 ± 1.6 (SD) l/min, haloperidol HVD = 9.9 ± 2.1 l/min;P = not significant, analysis ofvariance]. We conclude that combined central and peripheraldopamine-receptor antagonism in humans with haloperidol produces asimilar pattern of change to that reported previously with theperipheral antagonist domperidone. We have been unable to show inhumans a decrease in HVD by the centrally acting drug as observed incats.

     

Effects of daytime food intake on memory consolidation during sleep or sleep deprivation

Sleep enhances memory consolidation. Bearing in mind that food intake produces many metabolic signals that can influence memory processing in humans (e.g., insulin), the present study addressed the question as to whether the enhancing effect of sleep on memory consolidation is affected by the amount of energy consumed during the preceding daytime. Compared to sleep, nocturnal wakefulness has been shown to impair memory consolidation in humans. Thus, a second question was to examine whether the impaired memory consolidation associated with sleep deprivation (SD) could be compensated by increased daytime energy consumption. To these aims, 14 healthy normal-weight men learned a finger tapping sequence (procedural memory) and a list of semantically associated word pairs (declarative memory). After the learning period, standardized meals were administered, equaling either ～50% or ～150% of the estimated daily energy expenditure. In the morning, after sleep or wakefulness, memory consolidation was tested. Plasma glucose was measured both before learning and retrieval. Polysomnographic sleep recordings were performed by electroencephalography (EEG). Independent of energy intake, subjects recalled significantly more word pairs after sleep than they did after SD. When subjects stayed awake and received an energy oversupply, the number of correctly recalled finger sequences was equal to those seen after sleep. Plasma glucose did not differ among conditions, and sleep time in the sleep conditions was not influenced by the energy intake interventions. These data indicate that the daytime energy intake level affects neither sleep's capacity to boost the consolidation of declarative and procedural memories, nor sleep's quality. However, high energy intake was followed by an improved procedural but not declarative memory consolidation under conditions of SD. This suggests that the formation of procedural memory is not only triggered by sleep but is also sensitive to the fluctuations in the energy state of the body.     

An attempt to influence by drugs recovery sleep after sleep deprivation.

Rats were deprived of sleep by placing them for 36 hours in a slowly moving drum. After this procedure, during recovery sleep, the latency of onset of the first rhombencephalic - paradoxical sleep period decreased and the proportion of telencephalic/rhombencephalic - slow wave sleep reversed (during the first hour of recovery sleep). Repeated administration during the deprivation period of physostigmine (0,5 mg/kg i. p. in 30 min intervals 20-30 times) inducing in waking animals in EEG pattern close to that of rhombencephalic sleep, or atropine (1 mg/kg i. p. in 60 min intervals 10-15 times) evoking an activity resembling telencephalic sleep, did not change the above measures of recovery sleep. Pharmacologically induced sleep-like patterns did not substitute for the sleep the rats were deprived off.     

Effects of context on sleepiness self-ratings during repeated partial sleep deprivation

Ratings of subjective sleepiness are often used in laboratory and field studies of sleep loss and shifted sleep hours. Some studies suggest that such ratings might fail to reflect sleepiness as shown in physiology or performance. One reason for this may be the influence of the context of the rating. Social interaction or physical activity may mask latent sleepiness. The present study attempted to approach this question. Nine subjects participated in a partial sleep-deprivation experiment (five days of 4 h of time in bed [TIB]), preceded by two baseline days (8 h TIB) and followed by three recovery days (8 h TIB). Sleepiness was self-rated on the Karolinska Sleepiness Scale (KSS; scores of 1-9) after a period of relaxation, after a reaction-time test, and after 30 min of free activities. The results showed a strong increase in subjective sleepiness during sleep restriction and a significant difference between conditions. Free activity reduced the self-rated subjective sleepiness by 1.1 KSS units compared to the level of sleepiness self-rated at the end of the reaction-time test. Thus, the results of this study indicate that the context of a sleepiness rating affects the outcome of the rating.     

Arytenoideus muscle activity in normal adult humans during wakefulness and sleep

The respiratory-related activity of the arytenoideus (AR) muscle, a vocal cord adductor, was investigated in 10 healthy adults during wakefulness and sleep. AR activity was measured with intramuscular hooked-wire electrodes implanted by means of a fiber-optic nasopharyngoscope. Correct placement of the electrodes was confirmed by discharge patterns during voluntary maneuvers. The AR usually exhibited respiratory-related activity during quiet breathing in all awake subjects. Tonic activity was frequently present throughout the respiratory cycle. The pattern of phasic discharge during wakefulness exhibited considerable intrasubject variability both in timing and level of activity. Phasic activity usually began in midinspiration and terminated in mid- to late expiration. Periods of biphasic discharge were observed in four subjects. Phasic discharge primarily confined to expiration was also commonly observed. During quiet breathing in wakefulness, the level of phasic AR activity appeared to be directly related to the time of expiration. The AR was electrically silent in the six subjects who achieved stable periods of non-rapid-eye-movement sleep. Rapid-eye-movement sleep was observed in three subjects and was associated with sporadic paroxysmal bursts of AR activity. The results during wakefulness indicate that vocal cord adduction in expiration is an active phenomenon and suggest that the larynx may have an active role in braking exhalation.     

Susceptibility to periodic breathing with assisted ventilation during sleep in normal subjects

Assisted ventilation with pressure support (PSV)or proportional assist (PAV) ventilation has the potential to produceperiodic breathing (PB) during sleep. We hypothesized that PB willdevelop when PSV level exceeds the product of spontaneous tidal volume (VT) and elastance(VT_sp · E)but that the actual level at which PB will develop[PSV(PB)] will be influenced by thePCO₂ (difference between eupneicPCO₂ andCO₂ apneic threshold) and by RR[response of respiratory rate (RR) to PSV]. We also wishedto determine the PAV level at which PB develops to assess inherentventilatory stability in normal subjects. Twelve normal subjectsunderwent polysomnography while connected to a PSV/PAV ventilatorprototype. Level of assist with either mode was increased in smallsteps (2-5 min each) until PB developed or the subject awakened.End-tidal PCO₂,VT, RR, and airway pressure (Paw) were continuously monitored, and the pressure generated byrespiratory muscle (Pmus) was calculated. The pressure amplification factor (PAF) at the highest PAV level was calculated from[(Paw + Pmus)/Pmus], where Paw is peak Paw  continuous positive airway pressure. PB with central apneas developedin 11 of 12 subjects on PSV. PCO₂ranged from 1.5 to 5.8 Torr. Changes in RR with PSV were small andbidirectional (+1.1 to 3.5min¹). With use ofstepwise regression, PSV(PB) was significantly correlated withVT_sp(P = 0.001), E(P = 0.00009),PCO₂ (P = 0.007), and RR(P = 0.006). The final regressionmodel was as follows: PSV(PB) = 11.1 VT_sp + 0.3E  0.4 PCO₂  0.34 RR  3.4 (r = 0.98). PBdeveloped in five subjects on PAV at amplification factors of1.5-3.4. It failed to occur in seven subjects, despite PAF of upto 7.6. We conclude that 1) aPCO₂ apneic threshold exists duringsleep at 1.5-5.8 Torr below eupneicPCO₂,2) the development of PB during PSVis entirely predictable during sleep, and3) the inherent susceptibility to PBvaries considerably among normal subjects.

     

Partitioning of inhaled ventilation between the nasal and oral routes during sleep in normal subjects.

The oral and nasal contributions to inhaled ventilation were simultaneously quantified during sleep in 10 healthy subjects (5 men, 5 women) aged 43 +/- 5 yr, with normal nasal resistance (mean 2.0 +/- 0.3 cmH(2)O. l(-1). s(-1)) by use of a divided oral and nasal mask. Minute ventilation awake (5.9 +/- 0.3 l/min) was higher than that during sleep (5.2 +/- 0.3 l/min; P < 0.0001), but there was no significant difference in minute ventilation between different sleep stages (P = 0.44): stage 2 5.3 +/- 0.3, slow-wave 5.2 +/- 0.2, and rapid-eye-movement sleep 5.2 +/- 0.2 l/min. The oral fraction of inhaled ventilation during wakefulness (7.6 +/- 4%) was not significantly different from that during sleep (4.3 +/- 2%; mean difference 3.3%, 95% confidence interval -2.1-8.8%, P = 0.19), and no significant difference (P = 0.14) in oral fraction was observed between different sleep stages: stage two 5.1 +/- 2.8, slow-wave 4.2 +/- 1.8, rapid-eye-movement 3.1 +/- 1.7%. Thus the inhaled oral fraction in normal subjects is small and does not change significantly with sleep stage.