Pascal Van Beers

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.

Effects of Zolpidem and Zaleplon on Sleep, Respiratory Patterns and Performance at a Simulated Altitude of 4,000 m

The effects of zolpidem or zaleplon on sleep architecture, respiratory patterns and performance were assessed at a simulated altitude of 4,000 m. Twelve male healthy subjects spent 4 nights in a decompression chamber, 1 at sea level (baseline), 3 at 4,000 m to test zolpidem (10 mg), zaleplon (10 mg) and placebo, given 15 min before switching the lights off. Sleep and respiratory patterns were analysed using polysomnography. Cognitive and physical performance was examined the next morning at sea level conditions. The study demonstrates that both zolpidem and zaleplon improved slow wave sleep at altitude, with zolpidem showing more marked effects than zaleplon. Both agents did not adversely affect respiration at altitude during the night, or cognitive or physical performance the next morning at the dosages used in this study. Thus, climbers may safely use both hypnotic agents.

Hypoxic alterations of cortisol circadian rhythm in man after simulation of a long duration flight

Fatigue is often reported after long duration flights. Mild hypobaric hypoxia caused by pressurisation may be involved in this effect through disruption of circadian rhythms, independently of the number of time zones crossed. In this controlled crossover study, we assessed the effects of two levels of hypoxia equivalent to 8000 and 12,000 ft on the circadian rhythm of plasma cortisol, a marker of the circadian time structure. Sixteen healthy young male volunteers (23-39 years) were exposed in a hypobaric chamber for 8 h (08:00-16:00 h) to 8000 ft, followed 4 weeks later to 12,000 ft. Plasma cortisol was assayed during two 24-h cycles (control and hypoxic exposure) every 2h in all subjects. We found a significant change in the pattern of cortisol secretion during both hypoxic exposures, with an initial fall in cortisol followed by a transient rebound, whereas the phase and the 24-h mean level remained unchanged. The change in cortisol pattern followed the alterations in autonomic balance assessed by heart rate variability (HRV) spectral analysis. The normalised high frequencies and the low-to-high frequencies ratio showed a significant shift toward sympathetic dominance with some differences in time course for both altitudes studied. HRV analysis improved the interpretation of cortisol 24-h profiles. Our data, which strongly suggest that prolonged mild hypoxia alters the expression of cortisol circadian rhythm, should be taken into account to interpret secretory rhythm changes after transmeridian flights.

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.

Prolonged mild hypoxia modifies human circadian core body temperature and may be associated with sleep disturbances.

Fatigue is often reported after long-haul airplane flights. Hypobaric hypoxia, observed in pressurized cabins, may play a role in this phenomenon by altering circadian rhythms. In a controlled cross-over study, we assessed the effects of two levels of hypoxia, corresponding to cabin altitudes of 8000 and 12,000 ft, on the rhythm of core body temperature (CBT), a marker of circadian rhythmicity, and on subjective sleep. Twenty healthy young male volunteers were exposed for 8 h (08:00–16:00 h) in a hypobaric chamber to a cabin altitude of 8000 ft and, 4 weeks later, 12,000 ft. Each subject served as his own control. For each exposure, CBT was recorded by telemetry for two 24 h cycles (control and hypoxic exposure). After filtering out nonphysiological values, the individual CBT data were fitted with a five-order moving average before statistical group analysis. Sleep latency, sleep time, and sleep efficiency were studied by sleep logs completed every day in the morning. Our results show that the CBT rhythm expression was altered, mainly at 12,000 ft, with a significant increase of amplitude and a delay in the evening decline in CBT, associated with alterations of sleep latency. Mild hypoxia may therefore alter circadian structure and result in sleep disturbances. These results may explain in part the frequent complaints of prolonged post-flight fatigue after long flights, even when no time zones are crossed.

Hypoxic depression of melatonin secretion after simulated long duration flights in man.

Abstract:  Fatigue is often reported after long duration flights. Mild hypobaric hypoxia caused by pressurization may be involved in this effect through disruption of circadian rhythms, independent of the number of time zones crossed. In this controlled crossover study we assessed the effects of two levels of hypoxia equivalent to 8000 and 12,000 ft on the rhythm of plasma melatonin concentrations, a marker of circadian rhythmicity. Sixteen healthy young male volunteers (23–39 years) were exposed in a hypobaric chamber for 8 hr (08:00–16:00 hours) to 8000 ft, followed 4 wk later by 12,000 ft. Plasma melatonin was assayed over two 24‐hr cycles (control and hypoxic exposure) every 2 hr in all subjects. We found a significant decrease in the nocturnal melatonin peak after hypoxic exposure at both altitudes, and we found that this effect was age dependent for the 12,000‐ft exposure: the decrease was only seen in the younger subjects (23–28 years). Analysis of heart rate variability allowed us to demonstrate that the older and less trained subjects (29–39 yr) in our study exhibited a far greater increase in sympathetic tone than the younger subjects during the 12,000‐ft exposure. These results show that hypoxic depression of melatonin secretion may be influenced by individual factors such as age, physical fitness and sympathetic reactivity to hypoxia. Our findings suggest that hypoxia may by itself contribute at least in part to postflight fatigue after long duration flights, and to the clinical disorders of jet lag in transmeridian flights through its effects on the circadian system.

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).

Hypoxia‐induced changes in recovery sleep, core body temperature, urinary 6‐sulphatoxymelatonin and free cortisol after a simulated long‐duration flight

Fatigue and sleep disorders often occur after long‐haul flights, even when no time zones are crossed. In this controlled study, we assessed the effects of two levels of hypoxia (at 8000 ft and 12 000 ft) on recovery sleep. Core body temperature (CBT), a circadian marker, urinary 6‐sulphatoxymelatonin and free cortisol were studied in 20 young healthy male volunteers exposed for 8 h (08:00–16:00 hours) in a hypobaric chamber to a simulated cabin altitude of 8000 ft and, 4 weeks later, 12 000 ft. Each subject served as his own control. Sleep was recorded by polysomnography for three consecutive nights for each exposure. CBT was monitored by telemetry during the three 24‐h cycles (control, hypoxic exposure and recovery). Free urinary cortisol and 6‐sulphatoxymelatonin levels were assayed twice daily between 08:00 and 20:00 hours (day) and between 20:00 and 08:00 hours (night). We showed significant changes in circadian patterns of CBT at both altitudes, suggesting a phase delay, and changes in recovery sleep but only at 12 000 ft. We observed an increase in sleep onset latency which correlated positively with the increase in CBT levels during the first recovery night and a decrease in the duration of stage N2 (formerly S2), which correlated negatively with the mid‐range crossing time, a reliable phase marker of CBT rhythm. This study shows clearly the impact of hypobaric hypoxia on circadian time structure during air flights leading to a phase delay of CBT, independent of jet lag and consequences on sleep during recovery.

Impact of hypobaric hypoxia in pressurized cabins of simulated long-distance flights on the 24 h patterns of biological variables, fatigue, and clinical status

Long‐distance flights can cause a number of clinical problems in both passengers and crewmembers. Jet lag as well as mild hypoxia resulting from incomplete cabin pressurization could contribute to these problems. The objective of this study was to assess, using a chronobiological approach, the clinical impact of diurnal hypobaric, hypoxic exposure on fatigue and other common symptoms encountered during high‐altitude exposure and to measure changes in blood chemistry (i.e., plasma creatinine, urea, uric acid, sodium, calcium, phosphorus, glycemia, and lipids). Fourteen healthy, diurnally active (from 07:00 to 23:00 h) male volunteers, aged 23 to 39 yrs, spent 8.5 h in a hypobaric chamber (08:00 to 16:30 h), at a simulated altitude of 8,000 ft (2,438 m). This was followed by an additional 8.5 h of study four weeks later at a simulated altitude of 12,000 ft (3,658 m). Clinical data were collected every 2 h between 08:00 and 18:00 h, and biological variables were assayed every 2 h over two (control and hypoxic‐exposure) 24 h cycles. Clinical symptoms were more frequent with the 12,000 ft exposure. Wide interindividual variability was observed in the clinical tolerance to prolonged hypobaric hypoxia. The 24 h profiles of most biochemical variables were significantly altered at each altitude, with changes in mean plasma levels and a tendency toward phase delay, except for uric acid, which showed a phase advance. Changes in appetite mainly occurred with the simulated 12,000 ft exposure and may have been associated with changes in the postprandial glycemia profile. Finally, though the observed biochemical changes were significant, their clinical relevance must be clarified in studies involving actual long‐distance flights.

Energy Expenditure During an Ultraendurance Alpine Climbing Race

Abstract Objective.—Accurate reports of energy expenditure (EE) during prolonged mountaineering activity are sparse. The purpose of this study was to estimate EE during a winter ultraendurance climbing race and individual mountaineering activities in Mont Blanc, France. Methods.—Seven days before the race, resting metabolic rate (RMR) and maximal oxygen consumption (Vo2max) were measured in 10 experienced male climbers (30.0 ± 0.9 years). Three days before (reference period) and during the race, heart rate (HR) was recorded for estimation of total daily EE (TDEE), and the type and duration of all activities were collected through questionnaires. Total DEE was calculated by adding DEE during sleep (DEE sleep), sedentary (DEE sedentary), and during exercise (DEE exercise). Daily energy expenditure during exercise was determined through assumption of the rectilinear relationship between heart rate (HR) and Vo2. Anthropometric measurements were performed 7 days before, just before, and immediately after the race. Results.—Total time of the race averaged approximately 29 hours and 29 minutes, including 11 hours and 24 minutes in the hut, plus 18 hours and 5 minutes dedicated to climbing. During the race, TDEE was 43.6 ± 1.2 MJ·d−1. Energy expenditures for cross-country skiing and alpine climbing were similar (57.3 ± 2.1 kJ·min−1 and 54.0 ± 2.9 kJ·min−1, respectively). An energy deficit of 33.5 ± 2.3 MJ resulted after the race, with a mean weight loss of 1.52 ± 0.31 kg (P < .001). Conclusions.—Experienced climbers expended a high level of energy during a winter ultraendurance alpine climbing race at moderate altitude under high degrees of difficulty and risk exposure. These results provide comparative data on the energy cost of the main mountaineering activities during a race: cross-country skiing and alpine climbing.