Expiratory timing in obstructive sleep apnoeas

Diaphragmatic electromyogram was recorded during NREM sleep in 4 patients affected by obstructive sleep apnoea (OSA) syndrome in order to evaluate the behaviour of expiratory time (TE) in the course of the obstructive apnoea-ventilation cycle. The two components of TE, i.e. time of post-inspiratory inspiratory activity (TPIIA) and time of expiratory phase 2 (TE2) were separately analysed. TPIIA showed a short duration, with only minor variations, within the apnoea, while its duration was more variable and longer in the interapnoeic periods: the longest TPIIA values were associated with the highest inspiratory volumes in the same breaths. This behaviour seemed regulated according to the need of a more or less effective expiratory flow braking, probably as a result of pulmonary stretch receptors discharge. Conversely TE2 showed a continuous gradual modulation, progressively increasing in the pre-apnoeic period, decreasing during the apnoea and increasing in the post-apnoeic period: these TE2 variations seemed related to oscillations in chemical drive. These data show that TE in the obstructive apnoea-ventilation cycle results from a different modulation in its two components and suggest that both mechanical and chemical influences play a role in its overall duration.     

Spontaneous neural activity during human slow wave sleep

Slow wave sleep (SWS) is associated with spontaneous brain oscillations that are thought to participate in sleep homeostasis and to support the processing of information related to the experiences of the previous awake period. At the cellular level, during SWS, a slow oscillation (<1 Hz) synchronizes firing patterns in large neuronal populations and is reflected on electroencephalography (EEG) recordings as large-amplitude, low-frequency waves. By using simultaneous EEG and event-related functional magnetic resonance imaging (fMRI), we characterized the transient changes in brain activity consistently associated with slow waves (>140 μV) and delta waves (75–140 μV) during SWS in 14 non-sleep-deprived normal human volunteers. Significant increases in activity were associated with these waves in several cortical areas, including the inferior frontal, medial prefrontal, precuneus, and posterior cingulate areas. Compared with baseline activity, slow waves are associated with significant activity in the parahippocampal gyrus, cerebellum, and brainstem, whereas delta waves are related to frontal responses. No decrease in activity was observed. This study demonstrates that SWS is not a state of brain quiescence, but rather is an active state during which brain activity is consistently synchronized to the slow oscillation in specific cerebral regions. The partial overlap between the response pattern related to SWS waves and the waking default mode network is consistent with the fascinating hypothesis that brain responses synchronized by the slow oscillation restore microwake-like activity patterns that facilitate neuronal interactions.     

Cortical distribution of 2 delta frequencies in slow wave sleep

Many persons show two different types of delta-activity during synchronized sleep; these can already be differentiated visually as follows: one is located over the anterior brain areas, has a high frequency and is monomorph, the other one is located over the posterior brain areas, has a low frequency and is polymorph. However, both rhythms overlap considerably regarding their cortical distribution. The high high frequency delta-activity usually ranges from 1.5-2.9 Hz with a maximum at 2Hz; the one with low frequency ranges from 0.1-1.4 Hz with a maximum at 0.9 Hz. The interhemispheric coherence of the delta-activities is high with 0.7-0.9; for the anterior regions it is slightly higher than for the posterior ones. The intrahemispheric coherence is low, as was to be expected, and it is less than 0.3.     

Plasma growth hormone and slow wave sleep increase after interruption of sleep.

A comparison was made of plasma hGH and of sleep stages during one night of undistrubed sleep and one night in which sleep was interupted by an hour of enforced wakefulness folowing the end of the second NREM-REM sleep cycle in 8 normal subjects. Plasma was sampled at 15-min intervals. HGH and slow wave sleep were both significantly increased in the two cycles immediately following the period awake compared with the same two cycles during nights of uninterruped sleep. The difference arose predominantly in the fourth cycle of the night, i.e., in the second cycle after the sleep interuption. The findings are consistent with the belief that extra wakefulness brings additional sleep of high RESTORATIVE properties.     

Decreased slow wave sleep increases risk of developing hypertension in elderly men

The importance of sleep to health and cardiovascular disease has become increasingly apparent. Sleep-disordered breathing, sleep duration, and sleep architecture may all influence metabolism and neurohormonal systems, yet no previous study has evaluated these sleep characteristics concurrently in relation to incident hypertension. Our objective was to determine whether incident hypertension is associated with polysomnography measures of sleep-disordered breathing, sleep duration, and sleep architecture in older men. Participants were 784 community-dwelling, ambulatory men ≥65 years of age (mean age: 75.1±4.9 years) from the Outcomes of Sleep Disorders in Older Men Study who did not have hypertension at the time of their in-home polysomnography sleep studies (2003-2005) and who returned for follow-up (2007-2009). Of 784 older men included in this report, 243 met criteria for incident hypertension after a mean follow-up of 3.4 years. In unadjusted analyses, incident hypertension was associated with increased hypoxemia, increased sleep stages N1 and N2, and decreased stage N3 (slow wave sleep [SWS]). After adjustment for age, nonwhite race, study site, and body mass index, the only sleep index to remain significantly associated with incident hypertension was SWS percentage (odds ratio for lowest to highest quartile of SWS: 1.83 [95% CI: 1.18 to 2.85]). No attenuation of this association was seen after accounting for sleep duration, sleep fragmentation, and indices of sleep-disordered breathing. Percentage time in SWS was inversely associated with incident hypertension, independent of sleep duration and fragmentation, and sleep-disordered breathing. Selective deprivation of SWS may contribute to adverse blood pressure in older men.     

Haemodynamic responses to obstructive sleep apnoeas in premenopausal women.

OBJECTIVES: Obstructive apnoeas during sleep are associated with marked cyclical blood pressure fluctuations in men with obstructive sleep apnoea (OSA). Haemodynamic responses to OSA in women are largely unknown. We aimed to investigate haemodynamics during apnoeic events in women with OSA and to assess the influence of the menstrual cycle on these responses. DESIGN AND METHODS: Full overnight polysomnography and continuous non-invasive blood pressure monitoring was performed in 13 women with OSA during follicular and luteal phases of the menstrual cycle. Change in blood pressure (deltaBP) from pre- to post-apnoea termination was measured for each apnoeic cycle. RESULTS: Only 10 of 13 subjects ovulated. In women who ovulated, pressor responses to apnoea termination occurred in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, but substantially increased during the luteal phase of ovulatory cycles [NREM change in mean arterial pressure (deltaMAP) 12 +/- 3 mmHg during the follicular phase and 20 +/- 3 mmHg during the luteal phase, P < 0.001; REM deltaMAP 11 +/- 3 mmHg during the follicular phase and 23 +/- 3 mmHg during the luteal phase, P < 0.001]. Sleep apnoea severity did not change during the cycle in NREM sleep, but was reduced in REM during the luteal phase. Changes in pressor responses were absent in non-ovulating subjects. CONCLUSIONS: Obstructive apnoeas in women were associated with marked blood pressure changes, similar to those previously reported in men. While respiratory events improved slightly in the luteal phase, blood pressure responses to these events increased by approximately 100%. Thus, the menstrual cycle has discordant effects on the respiratory and cardiovascular effects of OSA in women.     

Milk ejection reflex linked to slow wave sleep in nursing rats.

Correlations between cerebral activity of nursing rats and the milk ejection reflex were studied in Sprague-Dawley rats with 15- to 17-day-old litters. The stretch reaction of the pups, which expresses the onset of milk ejection, was closely correlated with the slow sleep epochs of the mother. Once the litter started suckling, milk ejection only took place when the mother fell asleep and electroencephalographic features of slow wave sleep appeared. Milk ejection was never found during paradoxical sleep nor when the mother was awake. Sleep deprivation for 30 min impaired milk ejection in spite of continuous suckling of the nipples by the pups. If the mother was allowed to sleep immediately afterwards, ejection of milk occurred. A 24-h sleep-wakefulness pattern did not show differences between nursing and controls. Our results show that suckling, although necessary, is not enough to set off milk ejection. This reflex only appears when the mother falls asleep, suggesting that oxytocin release is linked to suckling and slow wave sleep.     

Distinct associations between energy balance and the sleep characteristics slow wave sleep and rapid eye movement sleep

Context:Epidemiologically, an inverse relationship between body mass index (BMI) and sleep duration is observed. Intra-individual variance in the amount of slow wave sleep (SWS) or rapid eye movement (REM) sleep has been related to variance of metabolic and endocrine parameters, which are risk factors for the disturbance of energy balance (EB).Objective:To investigate inter-individual relationships between EB (EB=∣energy intake-energy expenditure∣, MJ/24?h), SWS or REM sleep, and relevant parameters in normal-weight men during two 48?h stays in the controlled environment of a respiration chamber.Subjects and methods:A total of 16 men (age 23±3.7 years, BMI 23.9±1.9?kg?m(-2)) stayed in the respiration chamber twice for 48?h to assure EB. Electroencephalography was used to monitor sleep (2330-0730 hrs). Hunger and fullness were scored by visual analog scales; mood was determined by State Trait Anxiety Index-state and food reward by liking and wanting. Baseline blood and salivary samples were collected before breakfast. Subjects were fed in EB, except for the last dinner, when energy intake was ad libitum.Results:The subjects slept on average 441.8±49?min per night, and showed high within-subject reliability for the amount of SWS and REM sleep. Linear regression analyses showed that EB was inversely related to the amount of SWS (r=-0.43, P<0.03), and positively related to the amount of REM sleep (r=0.40, P<0.05). Relevant parameters such as hunger, reward, stress and orexigenic hormone concentrations were related to overeating, as well as to the amount of SWS and REM sleep, however, after inclusion of these parameters in a multiple regression, the amount of SWS and REM sleep did not add to the explained variance of EB, which suggests that due to their individual associations, these EB parameters are mediator variables.Conclusion:A positive EB due to overeating, was explained by a smaller amount of SWS and higher amount of REM sleep, mediated by hunger, fullness, State Trait Anxiety Index-state scores, glucose/insulin ratio, and ghrelin and cortisol concentrations.     

Effects of slow wave sleep on ventilatory compensation to inspiratory elastic loading

We determined the effects of slow wave sleep on ventilatory conpensation to inspiratory elastic loads 918 cm H₂O/L). Multiple loading trials of variable duration were applied in three healthy adult humans in wakefulness and during NREM sleep. During wakefulness, ventilatory response over 5 loaded breaths were highly variable. Tidal volume (V_T), mean inspiratory flow (Vt/Ti), and minute ventilation (V̇e) were preserved or increased in 2 of the 3 subjects in whom mouth occlusion pressure (P_0.1) was augmented in the immediated (second breath) response to the load. In ther third subjects who showed no changed in P_0.1, V̇e was not preserved during loading. During NREM sleep, the loading response was highly consistent in all trials and in all 3 subjects P_0.1 on the second loaded breath was not increased; thus V̇t and Vt/Ti were reduced over five loaded breaths. This absence of immediate loaded conpensation during NREM sleep was similar during normoxia, hyperoxia, and hypercapnia. During sustained loading in NREM sleep V̇t and Vt returned toward control levels coincident with an increase in end tidal CO₂We conclude that augmentation of respiratory neural drive sufficient for immediate compensation to elastic loads requires wakefulness. Compensatory responses to loading do not occur during NREM sleep until inmpiratory effort is augmented by chemical stimuli.     

The validity of the static charge sensitive bed in detecting obstructive sleep apnoeas

The demand for polysomnographic recordings associated with respiratory control exceeds the capacity of the few existing sleep disorder centres and therefore a simple and inexpensive method is needed for screening and diagnosing sleep-related breathing disorders. The static charge sensitive bed (SCSB) permits long-term recordings of body movements, respiratory movements and the ballistocardiogram (BCG) without electrodes or cables being attached to the subject. The aim of the present study was to test the validity of this particular method in detecting obstructive sleep apnoeas without airflow measurements. Simultaneous SCSB and spirometer recordings were compared in fourteen sleep apnoea patients and six controls. The mean sensitivity of the SCSB method to detect the obstructive apnoeas was 0.92-0.98. The specificity to detect 2 min apnoea epochs was 0.61-0.68 in the apnoea group, while in the control group it was 0.99-1.00. According to this study, the SCSB detects the obstructive events without always distinguishing between severe periodic hypopnoeas and obstructive apnoeas. The sensitivity of the SCSB makes it valuable for screening subjects suspected of having obstructive sleep apnoeas. Further studies will concentrate on a more detailed analysis of the various respiratory, BCG and body movement patterns, which may lead to additional information on the severity of the upper airway obstruction.     

Effects of selective slow wave sleep disruption on musculoskeletal pain and fatigue in middle aged women.

OBJECTIVE: To determine whether disrupted slow wave sleep (SWS) would evoke musculoskeletal pain, fatigue, and an alpha electroencephalograph (EEG) sleep pattern. We selectively deprived 12 healthy, middle aged, sedentary women without muscle discomfort of SWS for 3 consecutive nights. Effects were assessed for the following measures: polysomnographic sleep, musculoskeletal tender point pain threshold, skinfold tenderness, reactive hyperemia (inflammatory flare response), somatic symptoms, and mood state. METHODS: Sleep was recorded and scored using standard methods. On selective SWS deprivation (SWSD) nights, when delta waves (indicative of SWS) were detected on EEG, a computer generated tone (maximum 85 decibels) was delivered until delta waves disappeared. Musculoskeletal tender points were measured by dolorimetry; skinfold tenderness was assessed by skin roll procedure; and reactive hyperemia was assessed with a cotton swab test. Subjects completed questionnaires on bodily feelings, symptoms, and mood. RESULTS: On each SWSD night, SWS was decreased significantly with minimal alterations in total sleep time, sleep efficiency, and other sleep stages. Subjects showed a 24% decrease in musculoskeletal pain threshold after the third SWSD night. They also reported increased discomfort, tiredness, fatigue, and reduced vigor. The flare response (area of vasodilatation) in skin was greater than baseline after the first, and again, after the third SWSD night. However, the automated program for SWSD did not evoke an alpha EEG sleep pattern. CONCLUSION: Disrupting SWS, without reducing total sleep or sleep efficiency, for several consecutive nights is associated with decreased pain threshold, increased discomfort, fatigue, and the inflammatory flare response in skin. These results suggest that disrupted sleep is probably an important factor in the pathophysiology of symptoms in fibromyalgia.     

Worsening of obstructive sleep apnoeas in a patient with rheumatoid arthritis treated with anti-tumor necrosis factor

We report on a case of an adult patient treated for rheumatoid arthritis with infliximab, a chimerical monoclonal antibody to TNFalpha. Apart from this, the patient also showed clinical signs of obstructive sleep apnea syndrome that was confirmed by polysomnographic study. After infliximab treatment, additional sleep studies revealed an increase in the number of apneic events and SaO2 dips suggesting that TNFalpha plays an important role in the pathophysiology of sleep apnea. Thus, clinical recognition of sleep disordered breathing should be taken into account when rheumatoid arthritis patients are to be treated with infliximab.     

Source modeling sleep slow waves

Slow waves are the most prominent electroencephalographic (EEG) feature of sleep. These waves arise from the synchronization of slow oscillations in the membrane potentials of millions of neurons. Scalp-level studies have indicated that slow waves are not instantaneous events, but rather they travel across the brain. Previous studies of EEG slow waves were limited by the poor spatial resolution of EEGs and by the difficulty of relating scalp potentials to the activity of the underlying cortex. Here we use high-density EEG (hd-EEG) source modeling to show that individual spontaneous slow waves have distinct cortical origins, propagate uniquely across the cortex, and involve unique subsets of cortical structures. However, when the waves are examined en masse, we find that there are diffuse hot spots of slow wave origins centered on the lateral sulci. Furthermore, slow wave propagation along the anterior−posterior axis of the brain is largely mediated by a cingulate highway. As a group, slow waves are associated with large currents in the medial frontal gyrus, the middle frontal gyrus, the inferior frontal gyrus, the anterior cingulate, the precuneus, and the posterior cingulate. These areas overlap with the major connectional backbone of the cortex and with many parts of the default network.     

Effect of slow wave and REM sleep on thyropharyngeus and stylopharyngeus activity during induced central apneas

The pharyngeal constrictors have been hypothesized to play an important role in the regulation of upper airway (UAW) patency in patients with sleep apnea. However, little research has focused on the activation and control of muscles that determine the lateral and posterior wall of the retropalatal airway dimensions. Our aim was to investigate the effects of slow wave sleep (SWS) and rapid eye movement (REM) sleep on the activation of pharyngeal constrictor (thyropharyngeus; TP) and dilator (stylopharyngeus; SP) muscles during eupneic breathing and induced central apneas. In nine goats, we found that eupneic TP and SP activity progressively decreased from awake to SWS (57 and 56%, respectively; P<0.01) and further in REM (25.6 and 19.9%, respectively; P<0.01). In contrast, diaphragm activity decreased equally during SWS and REM (89.3 and 87.7%, respectively; P<0.01) compared to awake. Following induced apneas while SP activity was eliminated in every state, maximal TP activity was highest in awake state (318.6% of control; P<0.02), less in SWS (157.6%; P<0.02), and nearly absent in REM (117.3%; P>0.02). During the recovery from an induced apnea when diaphragm activity was at 95% of its' control, awake TP activity remained significantly elevated and SP reduced (P>0.02) while TP activity during SWS was elevated and SP had returned to control level. During REM, TP and SP activity were not different from their reduced controls (P>0.02). The data supports our hypotheses that SWS and REM sleep causes a reduction in the eupneic TP and SP activity, as well as a reduction in TP response to induced apneas. However, the relative imbalance in TP vs SP activity during the recovery from an apnea (awake and SWS) suggest that an imbalance of active neuromuscular forces may contribute to upper airway narrowing in mixed apneas, but not in central apnea during sleep.     

Clinical and cardiovascular characteristics of patients with obstructive sleep apnoeas without excessive daytime sleepiness

Objectives

To investigate whether patients with obstructive sleep apnoea (OSA) without excessive daytime sleepiness (EDS) have cardiovascular problems and different clinical characteristics from OSA with EDS.

Methods

Two groups of patients were compared retrospectively, one without EDS (Epworth <11) and another control group with EDS (Epworth>10), adjusted for sex, age, body mass index (BMI) and apnoea-hypopnoea index (AHI). The diurnal and nocturnal symptoms of OSA were analysed along with, polysomnography variables, prevalence of hypertension, diabetes mellitus, hyperlipaemia and history of previous cardiovascular events. A logistic regression was performed adjusted for multiple confounding factors to identify the variables associated with OSA without EDS.

Results

A total of 166 patients without EDS were studied (Epworth 7.2±2.4) and 295 with EDS (Epworth 14.5±2.5). In the adjusted multivariate logistic regression, OSA without EDS is independently associated with a feeling of restful sleep (95% CI: 1.70 to 3.93), less intellectual deterioration (95% CI: 0.30 to 0.95) and less effective sleep (95% CI: 0.96 to 0.99). No differences were found as regards prevalence of cardiovascular comorbidity, previous cardiovascular events, sleep structure or nocturnal clinical symptoms of OSA. When the patients who were in the extreme quartiles of the Epworth scale were analysed, the results obtained were equivalent to those of the whole series, with only intellectual deterioration disappearing from the final model.

Conclusions

After adjusting for confounding variables, OSA without EDS has a similar prevalence of cardiovascular comorbidities and less diurnal symptoms than OSA with EDS.     

Slow wave sleep in crayfish

Clear evidence of sleep in invertebrates is still meager. Defined as a distinct state of reduced activity, arousability, attention, and initiative, it is well established in mammals, birds, reptiles, and teleosts. It is commonly defined by additional electroencephalographic criteria that are only well established in mammals and to some extent in birds. Sleep states similar to those in mammals, except for electrical criteria, seem to occur in some invertebrates, based on behavior and some physiological observations. Currently the most compelling evidence for sleep in invertebrates (evidence that meets most standard criteria for sleep) has been obtained in the fruit fly Drosophila melanogaster. However, in mammals, sleep is also characterized by a brain state different from that at rest but awake. The electrophysiological slow wave criterion for this state is not seen in Drosophila or in honey bees. Here, we show that, in crayfish, a behavioral state with elevated threshold for vibratory stimulation is accompanied by a distinctive form of slow wave electrical activity of the brain, quite different from that during waking rest. Therefore, crayfish can attain a sleep state comparable to that of mammals.