Heterogeneity of human adaptations to bed rest and hypoxia: a retrospective analysis within the skeletal muscle oxidative function.

This retrospective study was designed to analyze the interindividual variability in the responses of different variables characterizing the skeletal muscle oxidative function to normoxic (N-BR) and hypoxic (H-BR) bed rests and to a hypoxic ambulatory confinement (H-AMB) of 10 and 21 days. We also assessed whether and how the addition of hypoxia to bed rest might influence the heterogeneity of the responses. In vivo measurements of O2 uptake and muscle fractional O2 extraction were carried out during an incremental one-leg knee-extension exercise. Mitochondrial respiration was assessed in permeabilized muscle fibers. A total of 17 subjects were included in this analysis. This analysis revealed a similar variability among subjects in the alterations induced by N-BR and H-BR both in peak O2 uptake (SD: 4.1% and 3.3% after 10 days; 4.5% and 8.1% after 21 days, respectively) and peak muscle fractional O2 extraction (SD: 5.9% and 7.3% after 10 days; 6.5% and 7.3% after 21 days), independently from the duration of the exposure. The individual changes measured in these variables were significantly related (r = 0.66, P = 0.004 after N-BR; r = 0.61, P = 0.009 after H-BR). Mitochondrial respiration showed a large variability of response after both N-BR (SD: 25.0% and 15.7% after 10 and 21 days) and H-BR (SD: 13.0% and 19.8% after 10 and 21 days); no correlation was found between N-BR and H-BR changes. When added to bed rest, hypoxia altered the individual adaptations within the mitochondria but not those intrinsic to the muscle oxidative function in vivo, both after the short- and medium-term exposures.

Do females and males exhibit a similar sarcopenic response as a consequence of normoxic and hypoxic bed rest?

NEW FINDINGS: What is the central question of this study? Do females and males exhibit a similar sarcopenic response as a consequence of normoxic and hypoxic bed rest? What is the main finding and its importance? During 10-day bed rest, exposure to a simulated (normobaric hypoxia) altitude of ∼4000 m does not exert additional significant structural or functional effect on the weight-bearing muscles in females compared to those noted under normoxic conditions. Whereas males and females exhibit decrements in muscle cross-sectional area and mass during normoxic and hypoxic bed rest, a concomitant strength decrement was only observed in males. ABSTRACT: This study investigated the effects of hypoxia on the known processes of adaptation of body composition and muscle function to normoxic inactivity. Females (n = 12) and males (n = 11) took part in the following interventions: hypoxic ambulation (HAMB; ∼4000 m); hypoxic bed rest (HBR; ∼4000 m) and normoxic bed rest (NBR). Prior to and immediately following each intervention, body composition, thigh and lower leg cross-sectional area (CSA) and isometric muscular strength were recorded. Participants lost body mass (HAMB: male -1.5 ± 0.9 kg, female -1.9 ± 0.7 kg; HBR: male -2.0 ± 1.8 kg, female -2.4 ± 0.8 kg; NBR: male -1.4 ± 1.3 kg, female -1.4 ± 0.9 kg) and lean mass (HAMB: male -3.9 ± 3.0%, female -3.4 ± 2.0%; HBR: male -4.0 ± 4.4%, female -4.1 ± 2.0%; NBR: male -4.0 ± 3.4%, female -2.2 ± 2.7%) with no between-condition or sex differences. Knee extension decreased for males in NBR compared to HAMB (HAMB: male -0.2 ± 9.1%, female 1.3 ± 4.9%; HBR: male -7.8 ± 10.3%, female -3.3 ± 10.9%; NBR: male -14.5 ± 11%, female -3.4 ± 6.9%). Loss of force during maximal voluntary contraction (MVC) in the knee extensors was significantly different between males and females following NBR. There were no other significant changes noted following the experimental interventions. There were no differences recorded between sexes in maximal MVC for elbow or ankle joints. Female lower leg CSA decreased following bed rest (HAMB: -4.5 ± 2.0%; HBR: -9.9 ± 2.6%; NBR: -8.0 ± 1.6%). These findings indicate that a 10-day hypoxic bed rest does not exert any significant additional effect on muscle atrophy when compared to NBR, except for female thigh CSA. In contrast to males, who exhibited a significant loss of muscle strength, no such decrement in strength was observed in the female participants.

Seasonal variation of temperature regulation: do thermoregulatory responses "spring" forward and "fall" back?

Seasonal variations in day length and light intensity can affect the circadian rhythm as well as some characteristics of temperature regulation. We investigated characteristics of autonomic (ATR), behavioural (BTR) and nocturnal (NTR) temperature regulation during spring and autumn. Eleven participants underwent experiments in both seasons. To assess ATR, participants performed a 30-min bout of submaximal upright exercise on a cycle ergometer, followed by 100 min of water immersion (28 °C). Thresholds for the onset of shivering and sweating and vasomotor response were measured. BTR was assessed using a water-perfused suit, with participants regulating the water-perfused suit temperature (Twps) within a range, considered as thermally comfortable. The Twps changed in a saw-tooth manner from 10 to 50 °C; by depressing a switch, the direction of the Twps changed, and this limit defined the thermal comfort zone (TCZ) for each participant. A 24-h proximal (calf)-distal (toe) skin temperature gradient (∆Tc-t) was measured to assess NTR. Initiation of vasomotor tone, shivering and sweating was similar between trials. Width of the TCZ was 8.1 °C in spring and 8.6 °C in autumn (p = 0.1), with similar upper and lower regulated temperatures. ∆Tc-t exhibited a typical circadian rhythm with no difference between seasons. Minor changes in skin temperature and oxygen consumption (p Ë‚ 0.05) between the seasons may indicate a degree of seasonal adaptation over the course of winter and summer, which persisted in spring and autumn. Other factors, such as country, race, sex and age could however modify the outcome of the study.

The LunHab project: Muscle and bone alterations in male participants following a 10 day lunar habitat simulation.

NEW FINDINGS: What is the central question of this study? It is well established that muscle and bone atrophy in conditions of inactivity or unloading, but there is little information regarding the effect of a hypoxic environment on the time course of these deconditioning physiological systems. What is the main finding and its importance? The main finding is that a horizontal 10 day bed rest in normoxia results in typical muscle atrophy, which is not aggravated by hypoxia. Changes in bone mineral content or in metabolism were not detected after either normoxic or hypoxic bed rest. ABSTRACT: Musculoskeletal atrophy constitutes a typical adaptation to inactivity and unloading of weightbearing bones. The reduced-gravity environment in future Moon and Mars habitats is likely to be hypobaric hypoxic, and there is an urgent need to understand the effect of hypoxia on the process of inactivity-induced musculoskeletal atrophy. This was the principal aim of the present study. Eleven males participated in three 10 day interventions: (i) hypoxic ambulatory confinement; (ii) hypoxic bed rest; and (iii) normoxic bed rest. Before and after the interventions, the muscle strength (isometric maximal voluntary contraction), mass (lean mass, by dual-energy X-ray absorptiometry), cross-sectional area and total bone mineral content (determined with peripheral quantitative computed tomography) of the participants were measured. Blood and urine samples were collected before and on the 1st, 4th and 10th day of the intervention and analysed for biomarkers of bone resorption and formation. There was a significant reduction in thigh and lower leg muscle mass and volume after both normoxic and hypoxic bed rests. Muscle strength loss was proportionately greater than the loss in muscle mass for both thigh and lower leg. There was no indication of bone loss. Furthermore, the biomarkers of resorption and formation were not affected by any of the interventions. There was no significant effect of hypoxia on the musculoskeletal variables. Short-term normoxic (10 day) bed rest resulted in muscular deconditioning, but not in the loss of bone mineral content or changes in bone metabolism. Hypoxia did not modify these results.

Ski-Everest (8848 m) Expedition: Digit Skin Temperature Responses to Cold Immersion May Reflect Susceptibility to Cold Injury.

INTRODUCTION: We tested the hypothesis that individual susceptibility to freezing cold injury might be reflected in an attenuated cold-induced vasodilatation (CIVD) response by comparing the CIVD responses of an elite alpinist with a history of freezing cold injury in the feet (case alpinist) with those of an age- and ability- matched noninjured alpinists control group (controls). According to this hypothesis, the vasomotor responses to a CIVD test of the case alpinist would represent a pathophysiological response when compared with the normal physiological response of a noninjured cohort. METHODS: The case alpinist and the controls in the cohort group conducted a cold water immersion test comprising sequential immersion of a hand and foot for 5 min in 35°C water, followed by a 30-min immersion in 8°C water and a 10-min recovery period in room air. During this test we monitored the finger and toe skin temperatures. RESULTS: The case alpinist had a significantly attenuated CIVD response and a lower skin temperature in all injured and noninjured digits during immersion (∼2°C lower than in the control group) and an attenuated recovery of finger skin temperatures (∼6°C lower than in the control group). CONCLUSIONS: The attenuated CIVD response of the case alpinist may reflect a previously unrecognized enhanced susceptibility to frostbite. In addition to the poor vasomotor response observed in the injured toes, he also exhibited a poor vasomotor response in his noninjured fingers. The results of the present study indicate that a test of vasomotor activity during thermal stress may identify individuals predisposed to cold injury.

Koroska 8000 Himalayan expedition: digit responses to cold stress following ascent to Broadpeak (Pakistan, 8051 m).

PURPOSE: Cold-induced vasodilatation (CIVD) is a peripheral blood flow response, observed in both the hands and feet. Exercise has been shown to enhance the response, specifically by increasing mean skin temperatures (Tsk), in part due to the increased number of CIVD waves. In contrast, hypobaric hypoxia has been suggested to impair digit skin temperature responses, particularly during subsequent hand rewarming following the cold stimulus. This study examined the combined effect of exercise and hypobaric hypoxia on the CIVD response. We compared the CIVD responses in the digits of both the hands and feet of a team of alpinists (N = 5) before and after a 35-day Himalayan expedition to Broadpeak, Pakistan (8051 m). METHODS: Five elite alpinists participated in hand and foot cold water immersion tests 20 days before and immediately upon return from their expedition. RESULTS: The alpinists summited successfully without supplemental oxygen. Post-expedition, all alpinists demonstrated higher minimum Tsk in their hands (pre: 9.9 ± 1.1, post: 10.1 ± 0.7 °C, p = 0.031). Four alpinists had either greater CIVD waves, and, consequently, higher mean Tsk in their hands, or higher recovery temperatures (pre: 26.0 ± 5.5 °C post: 31.0 ± 4.1 °C, p = 0.052), or faster rewarming rate (pre: 2.6 ± 0.5 °C min-1 post: 3.1 ± 0.4 °C min-1,p = 0.052). In the feet, the responses varied: 1/5 had higher wave amplitudes and 1/5 had higher passive recovery temperatures, whereas 3/5 had lower mean toe temperatures during cold exposure. CONCLUSIONS: The results of the cold stress test suggest after a 35-day Himalayan expedition, alpinists experienced a slight cold adaptation of the hands, but not the feet.

Cardiorespiratory Responses of Adults and Children during Normoxic and Hypoxic Exercise.

We aimed to elucidate potential differential effects of hypoxia on cardiorespiratory responses during submaximal cycling and simulated skiing exercise between adults and pre-pubertal children. Healthy, low-altitude residents (adults, N=13, Age=40±4yrs.; children, N=13, age=8±2yrs.) were tested in normoxia (Nor: PiO2=134±0.4 mmHg; 940 m) and normobaric hypoxia (Hyp: PiO2=105±0.6 mmHg; ~3 000 m) following an overnight hypoxic acclimation (≥12-hrs). On both days, the participants underwent a graded cycling test and a simulated skiing protocol. Minute ventilation (VE), oxygen uptake (VO2), heart rate (HR) and capillary-oxygen saturation (SpO2) were measured throughout both tests. The cycling data were interpolated for 2 relative workload levels (1 W·kg-1 & 2 W·kg-1). Higher resting HR in hypoxia, compared to normoxia was only noted in children (Nor:78±17; Hyp:89±17 beats·min-1; p<0.05), while SpO2 was significantly lower in hypoxia (Nor:97±1%; Hyp:91±2%; p<0.01) with no between-group differences. The VE, VO2 and HR responses were higher during hypoxic compared to normoxic cycling test in both groups (p<0.05). Except for greater HR during hypoxic compared to normoxic skiing in children (Nor:155±19; Hyp:167±13 (beats·min-1); p<0.05), no other significant between-group differences were noted during the cycling and skiing protocols. In summary, these data suggest similar cardiorespiratory responses to submaximal hypoxic cycling and simulated skiing in adults and children.

Circadian rhythm of peripheral perfusion during 10-day hypoxic confinement and bed rest.

INTRODUCTION: Future planetary habitats will be hypobaric and hypoxic to reduce the risk of decompression sickness during preparation for extra-vehicular activities. This study was part of a research programme investigating the combined effects of hypoxia and microgravity on physiological systems. PURPOSE: We tested the hypothesis that hypoxia-induced peripheral vasoconstriction persists at night and is aggravated by bed rest. Since sleep onset has been causally linked to nocturnal vasodilatation, we reasoned that hypoxia-induced vasoconstriction at night may explain sleep disturbances at altitude. Peripheral perfusion alterations as a consequence of bed rest may explain poor sleep quality reported during sojourns on the International Space Station. METHODS: Eleven males underwent three 10-day interventions in a randomised order: (1) hypoxic ambulatory confinement; (2) hypoxic bed rest; (3) normoxic bed rest. During each intervention we conducted 22-h monitoring of peripheral perfusion, as reflected by the skin temperature gradient. Measurements were conducted on the first (D 1) and last day (D 10) of each intervention. RESULTS: All interventions resulted in a decrease in daytime toe perfusion from D 1 to D 10. There was no difference in the magnitude of the daytime reduction in toe perfusion between the three interventions. There was a significant vasodilatation of the toes in all interventions by 11 pm. The fingertips remained well perfused throughout. CONCLUSIONS: Daytime vasoconstriction induced by hypoxia and/or bed rest is abolished at night, lending further support to the theory that changes in peripheral skin temperature may be functionally linked to sleep onset.

Comparison of joint kinematics between upright front squat exercise and horizontal squat exercise performed on a short arm human centrifugation.

This study compared the joint kinematics between the front squat (FS) conducted in the upright (natural gravity) position and in the supine position on a short arm human centrifuge (SAHC). Male participants (N = 12) with no prior experience exercising on a centrifuge completed a FS in the upright position before (PRE) and after (POST) a FS exercise conducted on the SAHC while exposed to artificial gravity (AG). Participants completed, in randomized order, three sets of six repetitions with a load equal to body weight or 1.25 × body weight for upright squats, and 1 g and 1.25 g at the center of gravity (COG) for AG. During the terrestrial squats, the load was applied with a barbell. Knee (left/right) and hip (left/right) flexion angles were recorded with a set of inertial measurement units. AG decreased the maximum flexion angle (MAX) of knees and hips as well as the range of motion (ROM), both at 1 and 1.25 g. Minor adaptation was observed between the first and the last repetition performed in AG. AG affects the ability to FS in naïve participants by reducing MAX, MIN and ROM of the knees and hip.

Retinal blood vessel diameters in children and adults exposed to a simulated altitude of 3,000 m.

Introduction: Technological advances have made high-altitude ski slopes easily accessible to skiers of all ages. However, research on the effects of hypoxia experienced during excursions to such altitudes on physiological systems, including the ocular system, in children is scarce. Retinal vessels are embryologically of the same origin as vessels in the brain, and have similar anatomical and physiological characteristics. Thus, any hypoxia-related changes in the morphology of the former may reflect the status of the latter. Objective: To compare the effect of one-day hypoxic exposure, equivalent to the elevation of high-altitude ski resorts in North America and Europe (∼3,000 m), on retinal vessel diameter between adults and children. Methods: 11 adults (age: 40.1 ± 4.1 years) and 8 children (age: 9.3 ± 1.3 years) took part in the study. They spent 3 days at the Olympic Sports Centre Planica (Slovenia; altitude: 940 m). During days 1 and 2 they were exposed to normoxia (FiO2 = 0.209), and day 3 to normobaric hypoxia (FiO2 = 0.162 ± 0.03). Digital high-resolution retinal fundus photographs were obtained in normoxia (Day 2) and hypoxia (Day 3). Central retinal arteriolar equivalent (CRAE) and venular equivalents (CRVE) were determined using an Automated Retinal Image Analyser. Results: Central retinal arteriolar and venular equivalents increased with hypoxia in children (central retinal arteriolar equivalent: 105.32 ± 7.72 µm, hypoxia: 110.13 ± 7.16 µm, central retinal venular equivalent: normoxia: 123.39 ± 8.34 µm, hypoxia: 130.11 ± 8.54 µm) and adults (central retinal arteriolar equivalent: normoxia: 105.35 ± 10.67 µm, hypoxia: 110.77 ± 8.36 µm; central retinal venular equivalent: normoxia: 126.89 ± 7.24 µm, hypoxia: 132.03 ± 9.72 µm), with no main effect of group or group*condition interaction. A main effect of condition on central retinal arteriolar and venular equivalents was observed (central retinal arteriolar equivalent:normoxia: 105.34 ± 9.30 µm, hypoxia: 110.50 ± 7.67 µm, p < 0.001; central retinal venular equivalent: normoxia: 125.41 ± 7.70 µm, hypoxia: 131.22 ± 9.05 µm, p < 0.001). Conclusion: A 20-hour hypoxic exposure significantly increased central retinal arteriolar and venular equivalents in adults and children. These hypoxia-induced increases were not significantly different between the age groups, confirming that vasomotor sensitivity of the retinal vessels to acute hypoxia is comparable between adults and prepubertal children.

Individual Variation Exists Within the Psychological Response to Hypoxic Bed Rest: A Retrospective Analysis.

Individual variation is of interest to Space Agency's, which cannot be explored with astronauts due to anonymity. We retrospectively analysed data collected throughout three projects (LunHab: 10-day male, PlanHab: 21-day male, and FemHab: 10-day female) to elucidate the potentially masked individual variation in the psychological responses to bed rest. The Profile of Mood State (POMS) and Positive and Negative Affect Schedule (PANAS) - instruments used to asses psychological state - and Lake Louise Mountain Sickness (LLMS) scores were collected prior to, following and throughout three interventions: 1: normoxic bed rest 2: hypoxic bed rest and 3: hypoxic ambulatory confinement. Total Mood Disturbance (TMD) was calculated from the POMS results, positive affect (PA), and negative affect (NA) from PANAS. The three instruments were included in a latent class mixed model. TMD, NA, and LLMS were included in a four-class model, with each class representing a specific type of response (Class 1: descending, Class 2: flat, Class 3: somewhat flat, Class 4: ascending). Responses for PA were assigned to only two classes (Classes 1 and 2). 54.55% or 24 participants were included in Class 2 (TMD, NA, and LLMS), where the responses did not change and neither hypoxia or activity level had a significant effect on emotional state. The remaining participants were allotted to Class 1, 3, or 4, where hypoxia was a significant covariate, while activity (bed rest) was significant only for class 3. For PA, 84.09% or 37 participants were assigned to class 2 indicating a significant effect of hypoxia on the participants responses with no effect of physical activity. Class 1 participants (n = 7) were not affected by hypoxia, however, physical activity improved their PA. Participants undergoing confinement, hypoxia and bed rest do not exhibit a uniform emotional response and may be categorised into 2-4 distinct classes. These results indicate significant individual emotional responses, that may be masked and underreported by traditional statistical approaches like means ± SD. The emotional state of our participants is a complex construct likely influenced by past experiences and different coping mechanisms which allowed some to adapt to the experimental environment more readily.

Validity and reliability of capillary vs. Venous blood for the assessment of haemoglobin mass and intravascular volumes.

Objectives: Haemoglobin mass (Hbmass) assessment with the carbon monoxide rebreathing method is a more accurate estimate than other measures of oxygen-carrying capacity. Blood may be collected by several means and differences in the measured variables may exist as a result. The present study assessed the validity and reliability of calculated Hbmass and intravascular volumes obtained from capillary blood (CAP) when compared to venous blood (VEN) draws. Methods: Twenty-two adults performed a carbon monoxide rebreathing procedure with paired VEN and CAP draws at baseline, pre-rebreathing and post-rebreathing (POST). Thirteen of these participants performed this protocol on two occasions to assess the data reliability from both blood sampling sites. In a second experiment, 14 adults performed a 20-min seated and a 20-min supine rest to assess for the effect of posture on haematological parameters. Results: Haemoglobin mass (CAP = 948.8 ± 156.8 g; VEN = 943.4 ± 157.3 g, p = 0.108) and intravascular volume (CAP = 6.5 ± 1 L; VEN = 6.5 ± 0.9 L, p = 0.752) were statistically indifferent, had low bias (Hbmass bias = 14.45 ± 40.42 g, LoA -64.78 g-93.67 g) and were highly correlated between sampling techniques. Reliability analysis demonstrated no difference in the mean change in variables calculated from both sampling sites and good to excellent intraclass correlation coefficients (>0.700), however, typical measurement error was larger in variables measured using CAP (VEN Hbmass TE% = 2.1%, CAP Hbmass TE% = 5.5%). The results indicate that a supine rest prior to the rebreathing protocol would have a significant effect on haemoglobin concentration and haematocrit values compared to a seated rest, with no effect on carboxyhaemoglobin %. Conclusion: The present study demonstrates that CAP and VEN were comparable for the calculation of Hbmass and intravascular volumes in terms of accuracy. However, reduced reliability and increased error in the CAP variables indicates that there are methodological considerations to address when deciding which blood drawing technique to utilise. To reduce this CAP error, increased replicate analyses are required.

Determination of exercise intensity domains during upright versus supine cycling: a methodological study.

Background: There is a growing interest among the research community and clinical practitioners to investigate cardiopulmonary exercise test (CPET) procedures and protocols utilized in supine cycling. Materials and Methods: The current study investigated the effects of posture on indicators of exercise intensity including gas exchange threshold (GET), respiratory compensation point (RCP), and the rate of peak oxygen uptake (V̇O2 peak), as well as the role of V̇O2 mean response time (MRT) in determining exercise intensity domains in nineteen healthy men (age: 22 ± 3 years). Two moderate-intensity step-transitions from 20 to 100 Watt (W) were completed, followed by a maximal CPET. After completing the ramp test, participants performed a constant-load at 90% of their attained peak power output (PPO). Results: No differences were observed in the V̇O2 MRT between the two positions, although the phase II-time constant (τV̇O2p) was 7 s slower in supine position compared to upright (p = 0.001). The rate of O2 uptake in the supine position at GET and RCP were lower compared to the upright position (208 ± 200 mL·min-1 (p = 0.007) and 265 ± 235 mL·min-1 (p = 0.012) respectively). Besides, V̇O2 peak was significantly decreased (by 6%, p = 0.002) during supine position. These findings were confirmed by the wide limits of agreement between the measures of V̇O2 in different postures (V̇O2 peak: -341 to 859; constant-load test: -528 to 783; GET: -375 to 789; RCP: -520 to 1021 all in mL·min-1). Conclusion: Since an accurate identification of an appropriate power output (PO) from a single-visit CPET remains a matter of debate, especially for supine cycling, we propose that moderate-intensity step-transitions preceding a ramp CPET could be a viable addition to ensure appropriate exercise-intensity domain determination, in particular upon GET-based prescription.

Adult Female Sleep During Hypoxic Bed Rest.

Purpose: Hypobaric hypoxic habitats are currently being touted as a potential solution to minimise decompression procedures in preparation for extra vehicular activities during future space missions. Since astronauts will live in hypoxic environments for the duration of such missions, the present study sought to elucidate the separate and combined effects of inactivity [simulated with the experimental bed rest (BR) model] and hypoxia on sleep characteristics in women. Methods: Twelve women (Age = 27 ± 3 year) took part in three 10-day interventions, in a repeated measures cross-over counterbalanced design: (1) normobaric normoxic BR (NBR), (2) normobaric hypoxic BR (HBR; simulated altitude of 4,000 m), and (3) normobaric hypoxic ambulatory (HAMB; 4,000 m) confinement, during which sleep was assessed on night 1 and night 10 with polysomnography. In addition, one baseline sleep assessment was performed. This baseline assessment, although lacking a confinement aspect, was included statistically as a fourth comparison (i.e., pseudo normobaric normoxic ambulatory; pNAMB) in the present study. Results: Hypoxia decreased sleep efficiency (p = 0.019), increased N1% sleep (p = 0.030), decreased N3 sleep duration (p = 0.003), and increased apnea hypopnea index (p < 0.001). BR impaired sleep maintenance, efficiency, and architecture [e.g., N2% sleep increased (p = 0.033)]. Specifically, for N3% sleep, the effects of partial pressure of oxygen and activity interacted. Hypoxia decreased N3% sleep both when active (pNAMB vs HAMB; p < 0.001) and inactive (NBR vs HBR; p = 0.021), however, this decrease was attenuated in the inactive state (-3.8%) compared to the active state (-10.2%). Conclusion: A 10-day exposure to hypoxia and BR negatively impacted sleep on multiple levels as in macrostructure, microstructure and respiratory functioning. Interestingly, hypoxia appeared to have less adverse effects on sleep macrostructure while the participants were inactive (bed ridden) compared to when ambulatory. Data were missing to some extent (i.e., 20.8%). Therefore, multiple imputation was used, and our results should be considered as exploratory.

Heterogeneity of Hematological Response to Hypoxia and Short-Term or Medium-Term Bed Rest.

Hematological changes are commonly observed following prolonged exposure to hypoxia and bed rest. Typically, such responses have been reported as means and standard deviations, however, investigation into the responses of individuals is insufficient. Therefore, the present study retrospectively assessed individual variation in the hematological responses to severe inactivity (bed rest) and hypoxia. The data were derived from three-bed rest projects: two 10-d (LunHab project: 8 males; FemHab project: 12 females), and one 21-d (PlanHab project: 11 males). Each project comprised a normoxic bed rest (NBR; PIO2=133mmHg) and hypoxic bed rest (HBR; PIO2=91mmHg) intervention, where the subjects were confined in the Planica facility (Ratece, Slovenia). During the HBR intervention, subjects were exposed to normobaric hypoxia equivalent to an altitude of 4,000m. NBR and HBR interventions were conducted in a random order and separated by a washout period. Blood was drawn prior to (Pre), during, and post bed rest (R1, R2, R4) to analyze the individual variation in the responses of red blood cells (RBC), erythropoietin (EPO), and reticulocytes (Rct) to bed rest and hypoxia. No significant differences were found in the mean ∆(Pre-Post) values of EPO across projects (LunHab, FemHab, and PlanHab; p>0.05), however, female EPO responses to NBR (Range - 17.39, IQR - 12.97 mIU.ml-1) and HBR (Range - 49.00, IQR - 10.91 mIU.ml-1) were larger than males (LunHab NBR Range - 4.60, IQR - 2.03; HBR Range - 7.10, IQR - 2.78; PlanHab NBR Range - 7.23, IQR - 1.37; HBR Range - 9.72, IQR - 4.91 mIU.ml-1). Bed rest duration had no impact on the heterogeneity of EPO, Rct, and RBC responses (10-d v 21-d). The resultant hematological changes that occur during NBR and HBR are not proportional to the acute EPO response. The following cascade of hematological responses to NBR and HBR suggests that the source of variability in the present data is due to mechanisms related to hypoxia as opposed to inactivity alone. Studies investigating hematological changes should structure their study design to explore these mechanistic responses and elucidate the discord between the EPO response and hematological cascade to fully assess heterogeneity.

Substantial and Reproducible Individual Variability in Skeletal Muscle Outcomes in the Cross-Over Designed Planica Bed Rest Program.

To evaluate the individual responses in skeletal muscle outcomes following bed rest, data from three studies (21-day PlanHab; 10-day FemHab and LunHab) were combined. Subjects (n = 35) participated in three cross-over campaigns within each study: normoxic (NBR) and hypoxic bed rest (HBR), and hypoxic ambulation (HAMB; used as control). Individual variability (SDIR) was investigated as √(SD Exp 2 -SD Con 2 ), where SDExp and SDCon are the standard deviations of the change score (i.e., post - pre) in the experimental (NBR and HBR) and the control (HAMB) groups, respectively. Repeatability and moderators of the individual variability were explored. Significant SDIR was detected for knee extension torque, and thigh and calf muscle area, which translated into an individual response ranging from 3 to -17% for knee extension torque, -2 to -12% for calf muscle area, and -1 to -8% for thigh muscle area. Strong correlations were found for changes in NBR vs. HBR (i.e., repeatability) in thigh and calf muscle area (r = 0.65-0.75, P < 0.0001). Change-scores in knee extension torque, and thigh and calf muscle area strongly correlated with baseline values (P < 0.001; r between -0.5 and -0.9). Orthogonal partial least squares regression analysis explored if changes in the investigated variables could predict calf muscle area alterations. This analysis indicated that 43% of the variance in calf muscle area could be attributed to changes in all of the other variables. This is the first study using a validated methodology to report clinically relevant individual variability after bed rest in knee extension torque, calf muscle area, and (to a lower extent) thigh muscle area. Baseline values emerged as a moderator of the individual response, and a global bed rest signature served as a moderately strong predictor of the individual variation in calf muscle area alterations.

The influence of a sustained 10-day hypoxic bed rest on cartilage biomarkers and subchondral bone in females: The FemHab study.

This study assessed the influence of a 10-day hypoxic bed rest on cartilage biomarkers and subchondral bone density across the patellofemoral joint (PFJ). Within clinical settings hypoxic tissue may arise in several types of disorders. Furthermore, a hypoxic environment is being considered for space flight habitats in the near future. Female participants (N = 12) participated in this study comprising three 10-day interventions: hypoxic ambulation (HAMB), normoxic bed rest (NBR), and hypoxic bed rest (HBR). Venous samples were collected prior to (day -2: Pre) and during the intervention (days 2 and 5), immediately before reambulation (D11) and 24 hr post intervention (R1). Blood samples were analyzed for: aggrecan, hyaluronan, Type IIA procollagen amino terminal propeptide (PIIANP), and cartilage oligomeric matrix protein (COMP). Total bone mineral density (BMD) in eight regions (2 mm × 10 mm) across the PFJ was determined. The three interventions (HAMB, HBR, and NBR) did not induce any significant changes in the cartilage biomarkers of hyaluronan or PIIANP. Aggrecan increased during the HAMB trial to 2.02 fold the Pre value. COMP decreased significantly in both NBR & HBR compared to HAMB on D5. There were significant differences in BMD measured across the PFJ from cortical patellar bone (735 to 800 mg/cm3 ) to femur trabecular (195 to 226 mg/cm3 ). However, there were no significant changes in BMD from Pre to Post bed rest. These results indicate that there were no significant detectable effects of inactivity/unloading on subchondral bone density. The biomarker of cartilage, COMP, decreased on D5, whereas the addition of hypoxia to bed rest had no effect, it appears that hypoxia in combination with ambulation counteracted this decrease.

Aerobic but not thermoregulatory gains following a 10-day moderate-intensity training protocol are fitness level dependent: A cross-adaptation perspective.

Moderate-intensity exercise sessions are incorporated into heat-acclimation and hypoxic-training protocols to improve performance in hot and hypoxic environments, respectively. Consequently, a training effect might contribute to aerobic performance gains, at least in less fit participants. To explore the interaction between fitness level and a training stimulus commonly applied during acclimation protocols, we recruited 10 young males of a higher (more fit-MF, peak aerobic power [VO2peak ]: 57.9 [6.2] ml·kg-1 ·min-1 ) and 10 of a lower (less fit-LF, VO2peak : 41.7 [5.0] ml·kg-1 ·min-1 ) fitness level. They underwent 10 daily exercise sessions (60 min@50% peak power output [Wpeak ]) in thermoneutral conditions. The participants performed exercise testing on a cycle ergometer before and after the training period in normoxic (NOR), hypoxic (13.5% Fi O2 ; HYP), and hot (35°C, 50% RH; HE) conditions in a randomized and counterbalanced order. Each test consisted of two stages; a steady-state exercise (30 min@40% NOR Wpeak to evaluate thermoregulatory function) followed by incremental exercise to exhaustion. VO2peak increased by 9.2 (8.5)% (p = .024) and 10.2 (15.4)% (p = .037) only in the LF group in NOR and HE, respectively. Wpeak increases were correlated with baseline values in NOR (r = -.58, p = .010) and HYP (r = -.52, p = .018). MF individuals improved gross mechanical efficiency in HYP. Peak sweat rate increased in both groups in HE, whereas MF participants activated the forehead sweating response at lower rectal temperatures post-training. In conclusion, an increase in VO2peak but not mechanical efficiency seems probable in LF males after a 10-day moderate-exercise training protocol.

The effect of thermal transience on the perception of thermal comfort.

INTRODUCTION: The present study tested the hypothesis that at any given ambient temperature (Ta), thermal comfort (TC) is not only a function of the temperature per se, but is also influenced by the temperatures rate of change and direction. METHODS: Twelve healthy young (age: 23 ±â€¯3) male participants completed experimental trials where Ta increased from 15° to 40 °C (heating) and then decreased from 40 to 15 °C (cooling). In one trial (FAST), the rate of change in Ta was maintained at 1 °C.min-1, and in the other (SLOW) at 0.5 °C.min-1. During each trial participants provided ratings of TC at 3-min intervals to determine their thermal comfort zone (TCZ). RESULTS: In the FAST trial, participants identified TCZ at an Ta between 22 ±â€¯4 and 30 ±â€¯4 °C during heating and between 25 ±â€¯3 and 33 ±â€¯3 °C during cooling phase (p = .003), and in the SLOW trial between 21 ±â€¯3 and 33 ±â€¯4 °C during heating and between 23 ±â€¯4 and 34 ±â€¯3 °C during cooling phase (p = .012). During the heating phase TCZ was established at a lower range of Ta, compared to cooling phase. The difference between the heating and cooling phases in preferred range of Ta was more pronounced in the FAST compared to SLOW trial. CONCLUSION: TCZ is influenced not only by the prevailing temperature, but also by the direction and the rate of the change in Ta. Faster changes in Ta (1 °C.min-1) established the TCZ at a higher Ta during cooling and at a lower Ta during heating phase.

Muscle Oxygenation During Hypoxic Exercise in Children and Adults.

INTRODUCTION: While hypoxia is known to decrease peak oxygen uptake ( V . ⁢ o 2 max) and maximal power output in both adults and children its influence on submaximal exercise cardiorespiratory and, especially, muscle oxygenation responses remains unclear. METHODS: Eight pre-pubertal boys (age = 8 ± 2 years.; body mass (BM) = 29 ± 7 kg) and seven adult males (age = 39 ± 4 years.; BM = 80 ± 8 kg) underwent graded exercise tests in both normoxic (PiO2 = 134 ± 0.4 mmHg) and hypoxic (PiO2 = 105 ± 0.6 mmHg) condition. Continuous breath-by-breath gas exchange and near infrared spectroscopy measurements, to assess the vastus lateralis oxygenation, were performed during both tests. The gas exchange threshold (GET) and muscle oxygenation thresholds were subsequently determined for both groups in both conditions. RESULTS: In both groups, hypoxia did not significantly alter either GET or the corresponding V . ⁢ o 2 at GET. In adults, higher V . E levels were observed in hypoxia (45 ± 6 l/min) compared to normoxia (36 ± 6 l/min, p < 0.05) at intensities above GET. In contrast, in children both the hypoxic V . E and V . ⁢ o 2 responses were significantly greater than those observed in normoxia only at intensities below GET (p < 0.01 for V . E and p < 0.05 for V . ⁢ o 2). Higher exercise-related heart rate (HR) levels in hypoxia, compared to normoxia, were only noted in adults (p < 0.01). Interestingly, hypoxia per se did not influence the muscle oxygenation thresholds during exercise in neither group. However, and in contrast to adults, the children exhibited significantly higher total hemoglobin concentration during hypoxic as compared to normoxic exercise (tHb) at lower exercise intensities (30 and 60 W, p = 0.01). CONCLUSION: These results suggest that in adults, hypoxia augments exercise ventilation at intensities above GET and might also maintain muscle blood oxygenation via increased HR. On the other hand, children exhibit a greater change of muscle blood perfusion, oxygen uptake as well as ventilation at exercise intensities below GET.