Fabien Sauvet

Basal blood pressure (BP) is partly determined by systemic vascular resistance, which is modulated by vasoactive pathways, including gaseous messengers. Carbon monoxide (CO), continuously generated by the constitutive enzyme heme oxygenase-2 (HO-2) encoded by HMOX2, promotes vascular smooth muscle relaxation and may contribute to interindividual variability in resting BP. The functional single-nucleotide polymorphism rs4786504_T>C has been associated with higher HMOX2 expression in C-allele carriers, providing a plausible biological link between genetic variation in the HO-2/CO pathway and vascular redox signaling. We investigated this association in forty young, healthy, normotensive adults studied under controlled laboratory conditions during a 4-day sleep deprivation protocol, with repeated standardized daytime BP measurements (478 observations). Linear mixed-effects models were adjusted for major physiological and behavioral covariates. T-allele carriers (C/T + T/T) exhibited higher diastolic BP (β = +6.08 mmHg, 95%CI [1.32–10.84], p = 0.017) and mean arterial pressure (β = +5.28 mmHg, 95%CI [0.28–10.29], p = 0.046) than C/C homozygotes, with no effect on systolic BP or heart rate. The association remained consistent across sensitivity and additive genetic models. This hypothesis-generating study provides preliminary evidence in humans, albeit limited by sample size, of a link between a functional HMOX2 variant and resting BP, consistent with a possible contribution of constitutive HO-2 activity to BP regulation.

The dynamics of recovery from impaired decision-making after total sleep deprivation (TSD) are not well understood. We investigated the impact of TSD and subsequent 3 h sleep recovery night period on decision-making. After one baseline night (8 h Time in Bed [TIB], 23:00–07:00), 40 study participants (50 per cent women) followed a sleep deprivation protocol including one night of TSD (40 h continuous awakening), followed by 3 h TIB sleep recovery period (23:00–02:00) and 8 h TIB sleep recovery period. Indices derived from reaction time (RT), Go/No-Go, and complex Go/No-Go tasks (involving perceptual components, motor responses, RT, and accuracy) were assessed daily during dual-choice decision-making tasks (MindPulse Digital Battery). Composite indices to describe executive speed, reaction to difficulty, speed/accuracy balance, and parameters from decision diffusion model analysis were recorded. Errors and RT increased after TSD and remained elevated after a 3-h sleep recovery night, particularly for Go/No-Go tasks. Anticipation and inhibition errors as well as speed/accuracy balance are not restored by 3 h sleep recovery night, whereas RT was restored. Lower decision diffusion model drift values (i.e. slower information accumulation) observed in the higher difficulty (complex Go/No-Go) after TSD, persisted after the 3-h recovery night. All parameters were restored after an 8-h TIB recovery night. No effect of sleep loss on executive speed and reaction to difficulty was observed. In conclusion, short sleep recovery partially restored decision-making alterations induced by TSD. Slower perceptual and motor processes that persist after a short recovery night may favor errors, with possible operational consequences for shift or on-call workers. Clinical trial: NCT05924737, https://clinicaltrials.gov/study/NCT05924737, 2023_RECOPS study, registered 2023-06-12 (Study start 2023-10-01). Clinical Trial Informations: Delta Waves and Cognitive Recovery (RECOPS), NCT05924737, https://clinicaltrials.gov/study/NCT05924737, study record: 2023-06-20, study start: 2023-10-01. Statement of Significance Sleep deprivation altered decision-making performance. In this work, we observed for the first time that a short sleep recovery (3 h Time in Bed) partially restored decision-making alterations induced by total sleep deprivation. The most complex tasks remained affected by sleep deprivation. The slowing down of perceptual and motor processes that persisted after a short night of recovery may have increased errors in decision-making, with possible operational consequences for shift workers or on-call workers.

Introduction: Sleep deprivation is known to induce cardiovascular responses. Several studies have shown the beneficial effect of caffeine on neurobehavioral performance during sleep deprivation, but less is known about its influence on the cardiovascular and inflammatory responses associated with sleep deprivation. The aim of this study is to evaluate the impact of acute caffeine intake on (1) peripheral blood pressures, and (2) heart rate, and cutaneous vascular conductance (CVC) and related biomarkers of endothelial activation, during total sleep deprivation (TSD), considering habitual caffeine consumption. Methods: 41 subjects followed a randomized, placebo-controlled, cross-over study and underwent 2 conditions of TSD (38 h), one with caffeine intake at 09:00 and 14:00 (2.5 mg/kg), and the other with placebo intake. Results: We confirm that TSD increases systolic and diastolic arterial pressures ( p = 0.001 and p = 0.002 for main effects respectively) and heart rate ( p = 0.001), and decreases endothelium-dependent and -independent CVC ( p = 0.001). Acute caffeine intake inflates the increase in arterial pressures and IL-6 levels, while it does not affect CVC and levels of E-selectin and monocyte chemotaxis protein-1 (MCP-1). Moreover, chronic caffeine consumption had significant main effects on systolic arterial pressure ( p = 0.03), heart rate ( p = 0.02), IL-6 levels ( p = 0.02), and acetylcholine (ACh)-induced CVC ( p = 0.02), and interacted with TSD on E-selectin levels and ACh-induced CVC ( p = 0.02 respectively). Conclusion: Acute caffeine intake provokes immuno-inflammatory and cardiovascular responses, and chronic caffeine consumption should be limited to the lowest efficient doses. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT03859882 , identifier NCT03859882.

The effect of sleep restriction (SR) on the physiological responses to normobaric hypoxia (NH) remains unknown. This study examined whether acute SR the night prior to a 5-h exposure to 3,500 m NH impacts (i) the resting ventilatory response, (ii) circulating pro- and anti-inflammatory cytokines, and (iii) their potential association. Seventeen healthy men (31 ± 7 yr; 77.1 ± 8.5 kg) were exposed to 5 h of NH (F_IO₂ = 13.6%, 3,500 m) in a randomized crossover design following one night of habitual (> 6 h) or restricted (≤ 3 h) sleep, separated by at least one week. Minute ventilation (V̇E), carbon dioxide output (V̇CO₂), oxygen uptake (V̇O₂), tidal volume (VT), and respiratory rate (RR) were assessed after 1.5 h of NH. Plasma cytokines (TNF-α, IL-8, IL-10) were measured following 1.5 h and 5 h of NH. SR increased VT (0.67 ± 0.34 vs. 0.63 ± 0.33 L, p = 0.031) following 1.5 h of NH. TNF-α was elevated following SR at both 1.5 h (0.98 ± 0.38 vs. 0.86 ± 0.41 pg/mL, p = 0.012) and 5 h (1.00 ± 0.45 vs. 0.79 ± 0.35 pg/mL, p = 0.004) of NH exposure. IL-10 levels increased after 5 h of NH following SR (0.94 ± 0.65 vs. 0.78 ± 0.73 pg/mL, p = 0.040). Ventilatory responses (VT, V̇E, V̇O₂, V̇CO₂, RER, V̇E/V̇O₂, V̇E/V̇CO₂, P_ETO₂, V̇A, SpO₂) positively correlated with IL-10 after 1.5 h of NH (r ranged from 0.433 to 0.659, p < 0.05). P_ETCO₂ negatively correlated with IL-10 (r = −0.411, p = 0.033). Acute SR modulates the ventilatory and inflammatory responses to NH which may influence altitude tolerance. IL-10 may influence ventilatory responses to NH. In this context, IL-10 is associated with ventilatory responses to NH.

Environmental high temperatures can strongly affect sleep. Our aim was to assess the protective effect of a High Heat Conductivity Mattress topper (HHCM) on sleep duration and quality during one night's exposure to heat. HHCM efficacy was studied in a randomised double‐blind crossover design in fifteen healthy young active subjects by overnight polysomnography in a temperature‐controlled sleep laboratory, during 4 nights: 2 nights at 22°C (HHCM and Control Mattress, CM) and 2 nights at 32°C (HHCM and CM). Core body temperature (CBT), skin, room and mattress toppers surface temperatures were continuously recorded. We observed interactions between temperature and mattress conditions. At 22°C, we did not show any beneficial effect of HHCM compared to CM on sleep duration, but a longer N3 sleep stage duration ( p = 0.03) and higher slow oscillation spectral density ( p = 0.03). Heat night exposure (32°C) induced a decrease in total sleep time (TST) (−24.8 ± 7.1 min, p = 0.02), rapid eye movement (REM) duration ( p = 0.03), sleep efficiency ( p = 0.04), delta power spectral density ( p = 0.03) and an increase of wake after sleep onset ( p = 0.03) and transition between stages rate ( p = 0.02). At 32°C, in comparison to CM, HHCM induced higher TST (+21.4 ± 16.1 min, p = 0.04), sleep efficiency ( p = 0.04), REM duration ( p = 0.03), and lower awakening duration ( p = 0.03). These effects were associated with lower skin temperature and CBT. In conclusion, HHCM improves sleep quality and has a protective effect on CBT and sleep patterns during heat exposure in active healthy subjects. It could be a countermeasure for promoting sleep in particular during heat waves.

Total sleep deprivation (TSD) alters local cold tolerance and could thus increase the risk of cold injury. We evaluated the impact of acute caffeine intake, the main countermeasure to TSD‐related deleterious effects, on local cold tolerance before and after TSD. Thirty‐six healthy subjects underwent two TSD protocols (i.e., continuous wakefulness), with randomized crossover intake of acute caffeine or placebo (2.5 mg/kg) administered twice during wakefulness. Before and after 33 h of TSD, finger (index and annular) temperature and skin blood flow were assessed during cold‐water immersion (CWI, 5°C, 20 min) followed by 20 min of rewarming in ambient air. We showed no significant effects of TSD on mean finger temperature during CWI in the placebo condition, but a significant reduction of the minimal temperature (8.86°C ± 0.35°C vs. 8.64°C ± 0.27°C, p = 0.02). During rewarming, we showed a reduction in temperature in the placebo condition (p = 0.02 for the mean temperature and p = 0.03 for the maximal) and an increase in the skin blood flow disparity between fingers at the four points of laser speckle rewarming measurements (p = 0.03). After TSD, acute caffeine intake (vs. placebo) increased mean (+2.11°C ± 0.21°C, p = 0.01) and minimal (+0.61°C ± 0.10°C, p = 0.02) finger temperatures during CWI, and improved rewarming after CWI (mean and maximal temperatures) (+2.28°C ± 0.08°C, p = 0.01, and +2.06°C ± 0.12°C, p = 0.02, respectively). Before TSD, acute caffeine intake significantly increased (vs. placebo) mean temperatures during CWI (p = 0.03) and reduced pain from the onset (p = 0.03) to the end of CWI (p = 0.02) and the first 2 min of rewarming (p = 0.04). There was also a significant main effect of habitual daily caffeine consumption on minimal finger temperatures during CWI, which decreased significantly between 0 and 600 mg consumption (R² = −0.43, p = 0.01), independently of the effects of day (before and after TSD) and treatment (caffeine and placebo conditions). These findings suggest that acute caffeine intake could be a protective countermeasure to local cold tolerance, particularly during TSD. However, habitual daily caffeine consumption is a factor of individual variability that should be recorded during CWI protocols. Clinical trial NCT03859882.