Fabien Sauvet

Effect of acute sleep deprivation on vascular function in healthy subjects

Sleep disorders are associated with inflammation and sympathetic activation, which are suspected to induce endothelial dysfunction, a key factor in the increased risk of cardiovascular disease. Less is known about the early effects of acute sleep deprivation on vascular function. We evaluated microvascular reactivity and biological markers of endothelial activation during continuous 40 h of total sleep deprivation (TSD) in 12 healthy men (29 +/- 3 yr). The days before [day 1 (D1)] and during TSD (D3), at 1200 and 1800, endothelium-dependent and -independent cutaneous vascular conductance was assessed by iontophoresis of acetylcholine and sodium nitroprusside, respectively, coupled to laser-Doppler flowmetry. At 0900, 1200, 1500, and 1800, heart rate (HR) and instantaneous blood pressure (BP) were recorded in the supine position. At D1, D3, and the day after one night of sleep recovery (D4), markers of vascular endothelial cell activation, including soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and interleukin-6 were measured from blood samples at 0800. Compared with D1, plasma levels of E-selectin were raised at D3, whereas intercellular adhesion molecule-1 and interleukin-6 were raised at D4 (P < 0.05). The endothelium-dependent and -independent CVC were significantly decreased after 29 h of TSD (P < 0.05). By contrast, HR, systolic BP, and the normalized low-frequency component of HR variability (0.04-0.15 Hz), a marker of the sympathetic activity, increased significantly within 32 h of TSD (P < 0.05). In conclusion, acute exposure to 40 h of TSD appears to cause vascular dysfunction before the increase in sympathetic activity and systolic BP.

Sleep and exercise: a reciprocal issue?

Sleep and exercise influence each other through complex, bilateral interactions that involve multiple physiological and psychological pathways. Physical activity is usually considered as beneficial in aiding sleep although this link may be subject to multiple moderating factors such as sex, age, fitness level, sleep quality and the characteristics of the exercise (intensity, duration, time of day, environment). It is therefore vital to improve knowledge in fundamental physiology in order to understand the benefits of exercise on the quantity and quality of sleep in healthy subjects and patients. Conversely, sleep disturbances could also impair a persons cognitive performance or their capacity for exercise and increase the risk of exercise-induced injuries either during extreme and/or prolonged exercise or during team sports. This review aims to describe the reciprocal fundamental physiological effects linking sleep and exercise in order to improve the pertinent use of exercise in sleep medicine and prevent sleep disorders in sportsmen.

Effect of one night of sleep loss on changes in tumor necrosis factor alpha (TNF-α) levels in healthy men

Total sleep deprivation in humans is associated with increased daytime sleepiness, decreased performance, elevations in inflammatory cytokines, and hormonal/metabolic disturbances. To assess the effects of 40 h of total sleep deprivation (TSD) under constant and well controlled conditions, on plasma levels of TNF-α and its receptor (TNFR1), interleukin-6 (IL-6), cortisol and C-reactive protein (CRP), sleepiness and performance, 12 healthy men (29±3 years) participated in a 5-days sleep deprivation experiment (two control nights followed by a night of sleep loss and one recovery night). Between 0800 and 2300 (i.e. between 25 and 40 h of sleep deprivation), a serial of blood sampling, multiple sleep latency, subjective levels of sleepiness and reaction time tests were completed before (day 2: D2) and after (day 4: D4) one night of sleep loss. We showed that an acute sleep deprivation (i.e. after 34 and 37 h of sleep deprivation) induced a significant increase in TNF-α (P<0.01), but there were no significant changes in TNFR1, IL-6, cortisol and CRP. In conclusion, our study in which constant and controlled experimental conditions were realized with healthy subjects and in absence of psychological or physical stressors, an acute total sleep deprivation (from 34 h) was sufficient to induce secretion of pro-inflammatory cytokine such as TNF-α, a marker more described in chronic sleep restriction or deprivation and as mediators of excessive sleepiness in humans in pathological conditions.

In flight automatic detection of vigilance states using a single EEG channel

Sleepiness and fatigue can reach particularly high levels during long-haul overnight flights. Under these conditions, voluntary or even involuntary sleep periods may occur, increasing the risk of accidents. The aim of this study was to assess the performance of an in-flight automatic detection system of lowvigilance states using a single electroencephalogram channel. Fourteen healthy pilots voluntarily wore a miniaturized brain electrical activity recording device during long-haul flights (10 ± 2.0 h, Atlantic 2 and Falcon 50 M, French naval aviation). No subject was disturbed by the equipment. Seven pilots experienced at least a periodofvoluntary(26.8 ± 8.0 min, n = 4)orinvoluntarysleep (N1 sleep stage, 26.6 ± 18.7 s, n = 7) during the flight. Automatic classification (wake/sleep) by the algorithm was made for 10-s epochs (O1-M2 or C3-M2 channel), based on comparison of means to detect changes in α, β, and θ relative power, or ratio [(α + θ)/β], or fuzzy logic fusion (α, β). Pertinence and prognostic of the algorithm were determined using epoch-by-epoch comparison with visual-scoring (two blinded readers, AASM rules). The best concordance between automatic detection and visualscoring was observed within the O1-M2 channel, using the ratio [(α + θ)/β] (98.3 ± 4.1% of good detection, K = 0.94 ± 0.07, with a 0.04 ± 0.04 false positive rate and a 0.87 ± 0.10 true positive rate). Our results confirm the efficiency of a miniaturized single electroencephalographic channel recording device, associated with an automatic detection algorithm, in order to detect low-vigilance states during real flights.

Napping Reverses the Salivary Interleukin-6 and Urinary Norepinephrine Changes Induced by Sleep Restriction

CONTEXT Neuroendocrine and immune stresses imposed by chronic sleep restriction are known to be involved in the harmful cardiovascular effects associated with poor sleep. OBJECTIVES Despite a well-known beneficial effect of napping on alertness, its effects on neuroendocrine stress and immune responses after sleep restriction are largely unknown. DESIGN This study was a strictly controlled (sleep-wake status, light environment, caloric intake), crossover, randomized design in continuously polysomnography-monitored subjects. SETTING The study was conducted in a laboratory-based study. PARTICIPANTS The subjects were 11 healthy young men. INTERVENTION We investigated the effects on neuroendocrine and immune biomarkers of a night of sleep restricted to 2 h followed by a day without naps or with 30 minute morning and afternoon naps, both conditions followed by an ad libitum recovery night starting at 20:00. MAIN OUTCOME MEASURES Salivary interleukin-6 and urinary catecholamines were assessed throughout the daytime study periods. RESULTS The increase in norepinephrine values seen at the end of the afternoon after the sleep-restricted night was not present when the subjects had the opportunity to take naps. Interleukin-6 changes observed after sleep deprivation were also normalized after napping. During the recovery day in the no-nap condition, there were increased levels of afternoon epinephrine and dopamine, which was not the case in the nap condition. A recovery night after napping was associated with a reduced amount of slow-wave sleep compared to after the no-nap condition. CONCLUSIONS Our data suggest that napping has stress-releasing and immune effects. Napping could be easily applied in real settings as a countermeasure to the detrimental health consequences of sleep debt.

Benefits of Sleep Extension on Sustained Attention and Sleep Pressure Before and During Total Sleep Deprivation and Recovery

OBJECTIVES To investigate the effects of 6 nights of sleep extension on sustained attention and sleep pressure before and during total sleep deprivation and after a subsequent recovery sleep. DESIGN Subjects participated in two experimental conditions (randomized cross-over design): extended sleep (EXT, 9.8 ± 0.1 h (mean ± SE) time in bed) and habitual sleep (HAB, 8.2 ± 0.1 h time in bed). In each condition, subjects performed two consecutive phases: (1) 6 nights of either EXT or HAB (2) three days in-laboratory: baseline, total sleep deprivation and after 10 h of recovery sleep. SETTING Residential sleep extension and sleep performance laboratory (continuous polysomnographic recording). PARTICIPANTS 14 healthy men (age range: 26-37 years). INTERVENTIONS EXT vs. HAB sleep durations prior to total sleep deprivation. MEASUREMENTS AND RESULTS Total sleep time and duration of all sleep stages during the 6 nights were significantly higher in EXT than HAB. EXT improved psychomotor vigilance task performance (PVT, both fewer lapses and faster speed) and reduced sleep pressure as evidenced by longer multiple sleep latencies (MSLT) at baseline compared to HAB. EXT limited PVT lapses and the number of involuntary microsleeps during total sleep deprivation. Differences in PVT lapses and speed and MSLT at baseline were maintained after one night of recovery sleep. CONCLUSION Six nights of extended sleep improve sustained attention and reduce sleep pressure. Sleep extension also protects against psychomotor vigilance task lapses and microsleep degradation during total sleep deprivation. These beneficial effects persist after one night of recovery sleep.

Acetylcholine chloride as a potential source of variability in the study of cutaneous vascular function in man.

INTRODUCTION Laser-Doppler flowmetry (LDF) coupled with acetylcholine chloride (ACh) iontophoresis is increasingly recognized as a reliable non-invasive method to study the endothelial function. However, ACh-vasodilation measurement appears highly variable possibly due to the ACh pharmacological properties itself. These problems may be partially overcome by using methacholine chloride (MCh), a more stable synthetic agonist of muscarinic receptors, instead of ACh. Therefore, we first studied the correlation between the two drugs and then the effects of (1) spatial variability (inter-site measurements), (2) temporal variability (inter-day measurements), (3) intra-day variability (morning versus evening), and (4) age on the variability of both ACh-vasodilation and MCh-vasodilation. METHODS The endothelium-dependent vasodilation response to simultaneous iontophoretic applications (4 doses of 10s at 0.1mA with 2min of current-free interval) of ACh (11mM) or MCh (10mM) was studied on the forearm of 40 healthy subjects (36 males, median 28yr, range 21-59yr). The percent change in perfusion (CVCpeak) from baseline and the area under the curve (CVC(AUC)) during iontophoresis were assessed. Inter-site, inter-day and intra-day coefficients of variation (CV) were studied for each drug as well as correlations between drugs and age. RESULTS A linear relationship was found between ACh- and MCh-CVCpeak (r²=0.75, p=0.01) and between ACh- and MCh-CVC(AUC) (r²=0.55, p=0.02). MCh inter-site CV for both CVCpeak (12.2%) and CVC(AUC) (13.8%) was significantly lower than ACh inter-site CV for CVCpeak (15.5%) and CVC(AUC) (15.3%), respectively. MCh inter-day CV for CVCpeak (17.2%) and CVC(AUC) (14.6%) was significantly lower than ACh inter-day CV for CVCpeak (19.7%) and ACh CVC(AUC) (21.2%). For ACh and MCh, the CVCpeak and CVC(AUC) were higher at 16:00pm than at 11:00am (p<0.05 for all). Finally, both ACh- and MCh-CVCpeak exhibited a logarithmic decrease with age (r²=0.61, p<0.01 and r²=0.58, p<0.01). CONCLUSION Although both drugs exhibited circadian and age variability, MCh exhibited less inter-site and interday variabilities than did ACh for the evaluation of cutaneous endothelium-dependent vasodilation. These findings should be taken into account in studies of cutaneous vascular function by iontophoresis coupled with laser Doppler flowmetry.

The Risks of Sleeping “Too Much”. Survey of a National Representative Sample of 24671 Adults (INPES Health Barometer)

Background A significant U-shaped association between sleep duration and several morbidity (obesity, diabetes or cardiovascular disease) and mortality risks has been regularly reported. However, although the physiological pathways and risks associated with “too short sleep” (<5 hours/day) have been well demonstrated, little is known about “too much sleeping”. Purpose To explore socio-demographic characteristics and comorbidities of “long sleepers” (over 10 hours/day) from a nationally representative sample of adults. Methods A cross-sectional nationally representative sample of 24,671 subjects from 15 to 85-year-old. An estimated total sleep time (TST) on non-leisure days was calculated based on a specifically designed sleep log which allows to distinguish “long sleepers” from “short sleepers” (<5 hours/day). Insomnia was assessed according to the International classification of sleep disorders (ICSD-2). Results The average TST was 7 hours and 13 minutes (+/− 17 minutes). Six hundred and twelve subjects were “long sleepers” (2.7%) and 1969 “short sleepers” (7.5%). Compared to the whole group, “long sleepers” were more often female, younger (15–25 year-old) or older (above 65 year-old), with no academic degree, mostly clerks and blue collar workers. “Long sleepers” were significantly more likely to have psychiatric diseases and a greater body mass index (BMI). However, long sleep was not significantly associated with the presence of any other chronic medical disease assessed. Conversely, short sleep duration was significantly associated with almost all the other chronic diseases assessed. Conclusions In the general population, sleeping too much was associated with psychiatric diseases and higher BMI, but not with other chronic medical diseases.

Vascular response to 1 week of sleep restriction in healthy subjects. A metabolic response

BACKGROUND Sleep loss may induce endothelial dysfunction, a key factor in cardiovascular risk. We examined the endothelial function during one week of sleep restriction and a recovery period (from 3-to-13 days) in healthy subjects, and its link to autonomic, inflammatory and/or endocrine responses. METHODS 12 men were followed at baseline (B1, 8-h sleep), after 2 (SR2) and 6 (SR6) days of SR (4-h sleep: 02:00-06:00) and after 1 (R1) and 12 (R12) recovery nights (8h sleep). At 10:00, we assessed changes in: arm cutaneous vascular conductance (CVC) induced by local application of methacholine (MCh), cathodal current (CIV) and heat (44°C), finger CVC and skin temperature (Tfi) during local cold exposure (5°C, 20-min) and passive recovery (22°C, 20-min). Blood samples were collected at 08:00. RESULTS Compared with baseline (B1), MCh and heat-induced maximal CVC values (CVC peak) were decreased at SR6 and R1. No effect of SR was observed for Tfi and CVC during immersion whereas these values were lower during passive recovery on SR6 and R1. From SR2 to R12, plasma concentrations of insulin, IGF-1 (total and free) and MCP-1 were significantly increased while those of testosterone and prolactin were decreased. Whole-blood blood mRNA concentrations of TNF-α and IL-1β were higher than B1. No changes in noradrenaline concentrations, heart rate and blood pressure were observed. CONCLUSIONS These results demonstrate that SR reduces endothelial-dependent vasodilatation and local tolerance to cold. This endothelial dysfunction is independent of blood pressure and sympathetic activity but associated with inflammatory and metabolic pathway responses (ClinicalTrials-NCT01989741).

Effect of Sleep Extension on the Subsequent Testosterone, Cortisol and Prolactin Responses to Total Sleep Deprivation and Recovery.

Total sleep deprivation (TSD) in humans is associated with altered hormonal levels, which may have clinical relevance. Less is known about the effect of an extended sleep period before TSD on these hormonal changes. Fourteen subjects participated in two experimental counterbalanced conditions (randomised cross‐over design): extended sleep (21.00–07.00 h time in bed, EXT) and habitual sleep (22.30–07.00 h time in bed, HAB). For each condition, subjects performed two consecutive phases: six nights of either EXT or HAB. These nights were followed by 3 days in the sleep laboratory with blood sampling at 07.00 and 17.00 h at baseline (B‐07.00 and B‐17.00), after 24 and 34 h of continuous awakening (24 h‐CA, 34 h‐CA) and after one night of recovery sleep (R‐07.00 and R‐17.00) to assess testosterone, cortisol, prolactin and catecholamines concentrations. At 24 h of awakening, testosterone, cortisol and prolactin concentrations were significantly lower compared to B‐07.00 and recovered basal levels after recovery sleep at R‐07.00 (P < 0.001 for all). However, no change was observed at 34 h of awakening compared to B‐17.00. No effect of sleep extension was observed on testosterone, cortisol and catecholamines concentrations at 24 and 34 h of awakening. However, prolactin concentration was significantly lower in EXT at B‐07.00 and R‐07.00 compared to HAB (P < 0.05, P < 0.001, respectively). In conclusion, 24 h of awakening inhibited gonadal and adrenal responses in healthy young subjects and this was not observed at 34 h of awakening. Six nights of sleep extension is not sufficient to limit decreased concentrations of testosterone and cortisol at 24 h of awakening but may have an impact on prolactin concentration.