Spaceflight Countermeasures Research Articles

Metabolic Cost of a Proposed NMES Spaceflight Countermeasure Compared to Walking in Active Adults.

INTRODUCTION: Astronauts exercise to reduce microgravity-induced bone loss, but the resultant skeletal loading may not be sufficient to reduce fracture risk on an extended Mars mission. Adding additional exercise increases the risk of a negative caloric balance. Neuromuscular electrical stimulation (NMES) induces involuntary muscle contractions, which load the skeleton. The metabolic cost of NMES is not fully understood. On Earth, walking is a common source of skeletal loading. If the metabolic cost of NMES were equal to or less than walking, it could offer a low metabolic cost option for increasing skeletal loading.METHODS:We measured the oxygen consumed and carbon dioxide produced from 10 subjects during 5-min bouts of walking at 2 mph, 3 mph, and 2 mph on a 6° incline, and of NMES to the legs at duty cycles of 1 s on and 5 s, 4 s, or 3 s off. Metabolic cost was calculated using the Brockway equation and the percent increase above resting for each NMES bout was compared to walking.RESULTS: Metabolic cost increased 64.9 ± 52.8% from rest in the most intense NMES duty cycle (1 s/3 s) and 120.4 ± 26.5%, 189.3 ± 59.5%, 281.7 ± 66.8%, for the 2 mph, 3 mph, and incline walking, respectively. The metabolic cost did not differ significantly between the three NMES duty cycles.DISCUSSION: The increase in metabolic cost of the fastest NMES bout was less than that of the slowest walk, indicating that numerous NMES bouts offer a way to increase skeletal loading at a modest metabolic cost. This might allow for more daily skeletal loading cycles, potentially further reducing bone loss.Abitante TJ, Alemi MM, Newman DJ, Duda KR. Metabolic cost of a proposed NMES spaceflight countermeasure compared to walking in active adults. Aerosp Med Hum Perform. 2023; 94(7):523-531.

Antiviral treatment with valacyclovir reduces virus shedding in saliva of Antarctic expeditioners

IntroductionReactivation of herpes viruses, such as Epstein–Barr virus (EBV), herpes simplex virus 1 (HSV1), and varicella zoster virus (VZV), increases in astronauts during spaceflight, compared with their preflight and postflight levels. Reactivations can increase the risk of associated clinical conditions, such as herpes zoster, chronic neuropathic pain, vision loss, stroke, cognitive impairment, and cold sores. Furthermore, continued viral shedding for longer periods after space travel may increase the risk of viral transmission to uninfected crew contacts, including, but not limited to, the immunocompromised and newborn infants. Thus, it is essential to develop spaceflight countermeasures to prevent herpes viral reactivations to ensure the health of crewmembers and their contacts. One such countermeasure is the prophylactic administration of an antiviral drug (valacyclovir) against the alpha herpesviruses (VZV and HSV1). To determine the effectiveness of this countermeasure, we studied the shedding of EBV, VZV, and HSV1 in Antarctic expeditioners, who have similar salivary viral shedding patterns during winter-over to astronauts during long spaceflights.MethodsThe efficacy of this antiviral drug as a countermeasure was determined using three major parameters in the saliva of expeditioners during winter-over with and without administration of this drug: (i) viral load and frequency, (ii) physiological stress biomarkers [i.e., levels of cortisol, dehydroepiandrosterone (DHEA), and amylase), and (iii) immune markers (i.e., inflammatory cytokines)]. Thirty-two volunteers from two Antarctic stations (McMurdo and South Pole) participated in this study. Participants were randomly assigned to either the treatment group (valacyclovir HCl: 1 g/day) or placebo group (oyster calcium: 500mg/day). ResultsViral shedding of EBV reduced significantly (> 24-fold) in the treatment group compared with the placebo group. HSV1 was also reduced by more than fivefold, but this was not statistically significant. No VZV shedding was observed in any of the participants. In the placebo group 50% of the saliva samples had measurable viral DNA (EBV, HSV1, or both), compared with 19% of the treatment group. There was no significant change in the ratio of cortisol to DHEA or levels of alpha-amylase, indicating that physiological stress was similar between the groups. No difference was detected in levels of salivary cytokines, except IL-10, which was found in significantly lower levels in the treatment group. DiscussionThese data indicate that valacyclovir is a safe and successful intervention to reduce EBV and HSV1 shedding in individuals subjected to extreme environments and stressors.

Potential of Neuromuscular Electrical Stimulation as a Bone Loss Countermeasure in Microgravity

INTRODUCTION: For future long-duration spaceflight missions, additional methods of loading the skeleton may be required to supplement exercise to minimize bone loss. Neuromuscular electrical stimulation (NMES) can elicit muscular contractions that create strain on bone. However, the potential effectiveness of NMES on the proximal femur during disuse is not known.METHODS: We measured the maximum isometric force of NMES-induced contractions of the rectus femoris and the hamstrings of 10 subjects (5 male, 5 female), sitting with the hips and knees at 90 degrees of flexion. We employed 2-D biomechanical models of the knee and hip to estimate the hip joint reaction forces, applied these forces to a generic femur finite element analysis model, and qualitatively compared the peak principal strains of the proximal femoral neck to the peak strains modeled in previous studies for other forms of exercise.RESULTS: The average peak tensile/compressive strains were 1380 ± 719 µε/-2179 ± 1130 µε and 573 ± 345 µε/-900 ± 543 µε for the male and female subjects, respectively. While results varied between studies, the strains achieved during NMES generally were comparable to those achieved during walking or stairs, with some individuals matching higher intensity activities.DISCUSSION: This study demonstrated that isometric NMES contractions of the thigh muscles can create strain in the proximal femoral neck similar to that achieved during low impact activities. While NMES alone will unlikely create a sufficient daily strain stimulus to prevent bone loss, it will likely improve the current spaceflight countermeasures by adding more frequent loading throughout the day.Abitante TJ, Bouxsein ML, Duda KR, Newman DJ. Potential of neuromuscular electrical stimulation as a bone loss countermeasure in microgravity. Aerosp Med Hum Perform. 2022; 93(11):774-782.

Gravitational Dose-Response Curves for Acute Cardiovascular Hemodynamics and Autonomic Responses in a Tilt Paradigm.

Background The cardiovascular system is strongly dependent on the gravitational environment. Gravitational changes cause mechanical fluid shifts and, in turn, autonomic effectors influence systemic circulation and cardiac control. We implemented a tilt paradigm to (1) investigate the acute hemodynamic response across a range of directions of the gravitational vector, and (2) to generate specific dose-response relationships of this gravitational dependency. Methods and Results Twelve male subjects were tilted from 45° head-up tilt to 45° head-down tilt in 15° increments, in both supine and prone postures. We measured the steady-state hemodynamic response in a range of variables including heart rate, stroke volume, cardiac output, oxygen consumption, total peripheral resistance, blood pressure, and autonomic indices derived from heart rate variability analysis. There is a strong gravitational dependence in almost all variables considered, with the exception of oxygen consumption, whereas systolic blood pressure remained controlled to within ≈3% across the tilt range. Hemodynamic responses are primarily driven by differential loading on the baroreflex receptors, combined with differences in venous return to the heart. Thorax compression in the prone position leads to reduced venous return and increased sympathetic nervous activity, raising heart rate, and systemic vascular resistance while lowering cardiac output and stroke volume. Conclusions Gravitational dose-response curves generated from these data provide a comprehensive baseline from which to assess the efficacy of potential spaceflight countermeasures. Results also assist clinical management of terrestrial surgery in prone posture or head-down tilt positions.

Effect of novel short-arm human centrifugation-induced gravitational gradients upon cardiovascular responses, cerebral perfusion and g-tolerance.

Key points The aim of this study was to determine the effect of rotational axis position (RAP and thus g‐gradient) during short‐arm human centrifugation (SAHC) upon cardiovascular responses, cerebral perfusion and g‐tolerance.In 10 male and 10 female participants, 10 min passive SAHC runs were performed with the RAP above the head (P1), at the apex of the head (P2), or at heart level (P3), with foot‐level Gz at 1.0 g, 1.7 g and 2.4 g.We hypothesized that movement of the RAP from above the head (the conventional position) towards the heart might reduce central hypovolaemia, limit cardiovascular responses, aid cerebral perfusion, and thus promote g‐tolerance.Moving the RAP footward towards the heart decreased the cerebral tissue saturation index, calf circumference and heart rate responses to SAHC, thereby promoting g‐tolerance.Our results also suggest that RAP, and thus g‐gradient, warrants further investigation as it may support use as a holistic spaceflight countermeasure. Artificial gravity (AG) through short‐arm human centrifugation (SAHC) has been proposed as a holistic spaceflight countermeasure. Movement of the rotational axis position (RAP) from above the head towards the heart may reduce central hypovolaemia, aid cerebral perfusion, and thus promote g‐tolerance. This study determined the effect of RAP upon cardiovascular responses, peripheral blood displacement (i.e. central hypovolaemia), cerebral perfusion and g‐tolerance, and their inter‐relationships. Twenty (10 male) healthy participants (26.2 ± 4.0 years) underwent nine (following a familiarization run) randomized 10 min passive SAHC runs with RAP set above the head (P1), at the apex of the head (P2), or at heart level (P3) with foot‐level Gz at 1.0 g, 1.7 g and 2.4 g. Cerebral tissue saturation index (cTSI, cerebral perfusion surrogate), calf circumference (CC, central hypovolaemia), heart rate (HR) and digital heart‐level mean arterial blood pressure (MAP) were continuously recorded, in addition to incidence of pre‐syncopal symptoms (PSS). ΔCC and ΔHR increases were attenuated from P1 to P3 (ΔCC: 5.46 ± 0.54 mm to 2.23 ± 0.42 mm; ΔHR: 50 ± 4 bpm to 8 ± 2 bpm, P < 0.05). In addition, ΔcTSI decrements were also attenuated (ΔcTSI: −2.85 ± 0.48% to −0.95 ± 0.34%, P < 0.05) and PSS incidence lower in P3 than P1 (P < 0.05). A positive linear relationship was observed between ΔCC and ΔHR with increasing +Gz, and a negative relationship between ΔCC and ΔcTSI, both independent of RAP. Our data suggest that movement of RAP towards the heart (reduced g‐gradient), independent of foot‐level Gz, leads to improved g‐tolerance. Further investigations are required to assess the effect of differential baroreceptor feedback (i.e. aortic–carotid g‐gradient).

Mobile Lower Body Negative Pressure Suit as an Integrative Countermeasure for Spaceflight.

BACKGROUND: Persistent headward fluid shift and mechanical unloading cause neuro-ocular, cardiovascular, and musculoskeletal deconditioning during long-term spaceflight. Lower body negative pressure (LBNP) reintroduces footward fluid shift and mechanical loading.METHODS: We designed, built, and tested a wearable, mobile, and flexible LBNP device (GravitySuit) consisting of pressurized trousers with built-in shoes to support ground reaction forces (GRF) and a thoracic vest to distribute load to the entire axial length of the body. In eight healthy subjects we recorded GRF under the feet and over the shoulders (Tekscan) while assessing cardiovascular response (Nexfin) and footward fluid shift from internal jugular venous cross-sectional area (IJVa) using ultrasound (Terason).RESULTS: Relative to normal bodyweight (BW) when standing upright, increments of 10 mmHg LBNP from 0 to 40 mmHg while supine induced axial loading corresponding to 0%, 13 ± 3%, 41 ± 5%, 75 ± 11%, and 125 ± 22% BW, respectively. Furthermore, LBNP reduced IJVa from 1.12 ± 0.3 cm² to 0.67 ± 0.2, 0.50 ± 0.1, 0.35 ± 0.1, and 0.31 ± 0.1 cm², respectively. LBNP of 30 and 40 mmHg reduced cardiac stroke volume and increased heart rate while cardiac output and mean arterial pressure were unaffected. During 2 h of supine rest at 20 mmHg LBNP, temperature and humidity inside the suit were unchanged (23 ± 1°C; 47 ± 3%, respectively).DISCUSSION: The flexible GravitySuit at 20 mmHg LBNP comfortably induced mechanical loading and desired fluid displacement while maintaining the mobility of hips and knee joints. The GravitySuit may provide a feasible method to apply low-level, long-term LBNP without interfering with daily activity during spaceflight to provide an integrative countermeasure.Petersen LG, Hargens A, Bird EM, Ashari N, Saalfeld J, Petersen JCG. Mobile lower body negative pressure suit as an integrative countermeasure for spaceflight. Aerosp Med Hum Perform. 2019; 90(12):993-999.

High-Intensity Exercise With Blood Flow Restriction or in Hypoxia as Valuable Spaceflight Countermeasures?

High-Intensity Exercise With Blood Flow Restriction or in Hypoxia as Valuable Spaceflight Countermeasures?

The Importance of Impact Loading and the Stretch Shortening Cycle for Spaceflight Countermeasures

Pronounced muscle and bone losses indicate that the musculoskeletal system suffers substantially from prolonged microgravity. A likely reason for these detrimental adaptations in the lower extremity is the lack of impact loading and the difficulty to apply large loading forces on the human body in microgravity. The human body is well adapted to ambulating in Earth’s gravitational field. A key principle herein is the periodic conversion of kinetic to elastic energy and vice versa. Predominantly tendons and to a lesser extent muscles, bones and other tissues contribute to this storage and release of energy, which is most efficient when organized in the stretch-shortening cycle (SSC). During SSC, muscles, especially those encompassing the ankle, knee, and hip joints, are activated in a specific manner, thereby enabling the production of high muscle forces and elastic energy storage. In consequence, the high forces acting throughout the body deform the viscoelastic biological structures sensed by mechanoreceptors and feedback in order to regulate the resilience of these structures and keep strains and strain rates in an uncritical range. Recent results from our lab indicate, notably, that SSC can engender a magnitude of tissue strains that cannot be achieved by other types of exercise. The present review provides an overview of the physiology and mechanics of the natural SSC as well as the possibility to mimic it by the application of whole-body vibration. We then report the evidence from bed rest studies on effectiveness and efficiency of plyometric and resistive vibration exercise as a countermeasure. Finally, implications and applications of both training modalities for human spaceflight operations and terrestrial spin-offs are discussed.

Herpes Virus Reactivation in Astronauts During Spaceflight and Its Application on Earth.

Latent herpes virus reactivation has been demonstrated in astronauts during shuttle (10–16 days) and International Space Station (≥180 days) flights. Following reactivation, viruses are shed in the body fluids of astronauts. Typically, shedding of viral DNA is asymptomatic in astronauts regardless of mission duration; however, in some cases, live/infectious virus was recovered by tissue culture that was associated with atopic-dermatitis or skin lesions during and after spaceflight. Hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes activation during spaceflight occurs as indicated by increased levels of stress hormones including cortisol, dehydroepiandrosterone, epinephrine, and norepinephrine. These changes, along with a decreased cell mediated immunity, contribute to the reactivation of latent herpes viruses in astronauts. Currently, 47/89 (53%) astronauts from shuttle-flights and 14/23 (61%) astronauts from ISS missions shed one or more herpes viruses in saliva/urine samples. Astronauts shed Epstein–Barr virus (EBV), varicella-zoster virus (VZV), and herpes-simplex-1 (HSV-1) in saliva and cytomegalovirus (CMV) in urine. Larger quantities and increased frequencies for these viruses were found during spaceflight as compared to before or after flight samples and their matched healthy controls. The shedding did not abate during the longer ISS missions, but rather increased in frequency and amplitude. These findings coincided with the immune system dysregulation observed in astronauts from shuttle and ISS missions. VZV shedding increased from 41% in space shuttle to 65% in ISS missions, EBV increased 82 to 96%, and CMV increased 47 to 61%. In addition, VZV/CMV shed ≤30 days after ISS in contrast to shuttle where VZV/CMV shed up to 5 and 3 days after flight respectively. Continued shedding of infectious-virus post-flight may pose a potential risk for crew who may encounter newborn infants, sero-negative adults or any immunocompromised individuals on Earth. Therefore, developing spaceflight countermeasures to prevent viral reactivation is essential. Our spaceflight-developed technologies for saliva collection/rapid viral detection have been extended to include clinical applications including zoster patients, chicken pox, post-herpetic neuralgia, multiple sclerosis, and various neurological disorders. These protocols are employed in various clinics and hospitals including the CDC and Columbia University in New York, as well as overseas in Switzerland and Israel.

High-Intensity Exercise Mitigates Cardiovascular Deconditioning During Long-Duration Bed Rest.

Head-down-tilt bed rest (HDT) mimics the changes in hemodynamics and autonomic cardiovascular control induced by weightlessness. However, the time course and reciprocal interplay of these adaptations, and the effective exercise protocol as a countermeasure need further clarification. The overarching aim of this work (as part of a European Space Agency sponsored long-term bed rest study) was therefore to evaluate the time course of cardiovascular hemodynamics and autonomic control during prolonged HDT and to assess whether high-intensity, short-duration exercise could mitigate these effects. A total of n = 23 healthy, young, male participants were randomly allocated to two groups: training (TRAIN, n = 12) and non-training (CTRL, n = 11) before undergoing a 60-day HDT. The TRAIN group underwent a resistance training protocol using reactive jumps (5–6 times per week), whereas the CTRL group did not perform countermeasures. Finger blood pressure (BP), heart rate (HR), and stroke volume were collected beat-by-beat for 10 min in both sitting and supine positions 7 days before HDT (BDC−7) and 10 days after HDT (R+10), as well as on the 2nd (HDT2), 28th (HDT28), and 56th (HDT56) day of HDT. We investigated (1) the isolated effects of long-term HDT by comparing all the supine positions (including BDC−7 and R+10 at 0 degrees), and (2) the reactivity of the autonomic response before and after long-term HDT using a specific postural stimulus (i.e., supine vs. sitting). Two-factorial linear mixed models were used to assess the time course of HDT and the effect of the countermeasure. Starting from HDT28 onwards, HR increased (p < 0.02) and parasympathetic tone decreased exclusively in the CTRL group (p < 0.0001). Moreover, after 60-day HDT, CTRL participants showed significant impairments in increasing cardiac sympathovagal balance and controlling BP levels during postural shift (supine to sitting), whereas TRAIN participants did not. Results show that a 10-day recovery did not compensate for the cardiovascular and autonomic deconditioning following 60-day HDT. This has to be considered when designing rehabilitation programs—not only for astronauts but also in general public healthcare. High-intensity, short-duration exercise training effectively minimized these impairments and should therefore deserve consideration as a cardiovascular deconditioning countermeasure for spaceflight.

Human Performance in Altered-Gravity Environments

Human Performance in Altered-Gravity Environments

Lower-body negative pressure decreases noninvasively measured intracranial pressure and internal jugular vein cross-sectional area during head-down tilt.

Long-term spaceflight induces a near visual acuity change in ~50% of astronauts. In some crew members, postflight cerebrospinal fluid (CSF) opening pressures by lumbar puncture are as high as 20.9 mmHg; these members demonstrated optic disc edema. CSF communicates through the cochlear aqueduct to affect perilymphatic pressure and tympanic membrane motion. We hypothesized that 50 mmHg of lower-body negative pressure (LBNP) during 15° head-down tilt (HDT) would mitigate elevations in internal jugular vein cross-sectional area (IJV CSA) and intracranial pressure (ICP). Fifteen healthy adult volunteers were positioned in sitting (5 min), supine (5 min), 15° HDT (5 min), and 15° HDT with LBNP (10 min) postures for data collection. Evoked tympanic membrane displacements (TMD) quantified ICP noninvasively. IJV CSA was measured using standard ultrasound techniques. ICP and IJV CSA increased significantly from the seated upright to the 15° HDT posture (P < 0.05), and LBNP mitigated these increases. LBNP at 25 mmHg reduced ICP during HDT (TMD of 322.13 ± 419.17 nl) to 232.38 ± 445.85 nl, and at 50 mmHg ICP was reduced further to TMD of 199.76 ± 429.69 nl. In addition, 50 mmHg LBNP significantly reduced IJV CSA (1.50 ± 0.33 cm2) during 15° HDT to 0.83 ± 0.42 cm2 LBNP counteracts the headward fluid shift elevation of ICP and IJV CSA experienced during microgravity as simulated by15° HDT. These data provide quantitative evidence that LBNP shifts cephalic fluid to the lower body, reducing IJV CSA and ICP.NEW & NOTEWORTHY The current study provides new evidence that 25 or 50 mmHg of lower body negative pressure reduces jugular venous pooling and intracranial pressure during simulated microgravity. Therefore, spaceflight countermeasures that sequester fluid to the lower body may mitigate cephalic venous congestion and vision impairment.

Hypovolemic men and women regulate blood pressure differently following exposure to artificial gravity

In addition to serious bone, vestibular, and muscle deterioration, space flight leads to cardiovascular dysfunction upon return to gravity. In seeking a countermeasure to space flight-induced orthostatic intolerance, we previously determined that exposure to artificial gravity (AG) training in a centrifuge improved orthostatic tolerance of ambulatory subjects. This protocol was more effective in men than women and more effective when subjects exercised. We now determine the orthostatic tolerance limit (OTL) of cardiovascularly deconditioned (furosemide) men and women on one day following 90 min of AG compared to a control day (90 min of head-down bed rest, HDBR). There were three major findings: a short bout of artificial gravity improved orthostatic tolerance of hypovolemic men (30 %) and women (22 %). Men and women demonstrated different mechanisms of cardiovascular regulation on AG and HDBR days; women maintained systolic blood pressure the same after HDBR and AG exposure while men's systolic pressure dropped (11 ± 2.9 mmHg) after AG. Third, as presyncopal symptoms developed, men's and women's cardiac output and stroke volume dropped to the same level on both days, even though the OTL test lasted significantly longer on the AG day, indicating cardiac filling as a likely variable to trigger presyncope. (1) Even with gender differences, AG should be considered as a space flight countermeasure to be applied to astronauts before reentry into gravity, (2) men and women regulate blood pressure during an orthostatic stress differently following exposure to artificial gravity and (3) the trigger for presyncope may be cardiac filling.

Lower Body Negative Pressure Counters Simulated Microgravity‐Induced Elevations of Intracranial Pressure

Ophthalmic evaluations of 7 astronauts after 6‐month missions to International Space Station show unexpected vision impairment. Lumbar punctures in 4 astronauts showed elevations of cerebrospinal fluid pressure after flight. We hypothesized that lower body negative pressure (LBNP) would counteract head down, head‐down tilt (HDT), induced elevations in intracranial pressure (ICP). Ten healthy volunteers participated in this study (mean age: 34 years) after IRB review. Cerebral and Cochlear Fluid Pressure (CCFP, noninvasive ICP surrogate) device determined relative changes in ICP. ICP, arm blood pressure, and heart rate were measured during the last minute of each condition. Subjects were positioned supine (5 mins), sitting (5 mins), 15‐degrees HDT (5 mins) and ten minutes of HDT with LBNP (25 mmHg). RMANOVA determined statistical significance (p&lt;0.05). ICP significantly increased from the sitting to the supine posture, p=0.028. Moreover, ICP further increased when the subjects were positioned in HDT, p=0.005. However, when LBNP was activated during HDT, ICP decreased and was not significantly different from supine levels (p=0.549). Mean blood pressure and heart rate did not change significantly across all conditions. In conclusion, short duration exposures to simulated microgravity increase ICP significantly and importantly, LBNP counteracts these elevations of ICP. Therefore, spaceflight countermeasures that shift fluid to the lower body may mitigate vision problems. This project was supported by NSBRI through NASA NCC 9‐58 (to BRM), APS Undergraduate Summer Research Fellowship (to EMC), and NASA grant NNX13AJ12G (to ARH).

Treatment of hydrogen molecule abates oxidative stress and alleviates bone loss induced by modeled microgravity in rats

Treatment with molecular hydrogen alleviates microgravity-induced bone loss through abating oxidative stress, restoring osteoblastic differentiation, and suppressing osteoclast differentiation and osteoclastogenesis. Recently, it has been suggested that hydrogen gas exerts a therapeutic antioxidant activity by selectively reducing cytotoxic reactive oxygen species (ROS). The aim of the present study was to elucidate whether treatment with molecular hydrogen alleviated bone loss induced by modeled microgravity in rats. Hindlimb suspension (HLS) and rotary wall vessel bioreactor were used to model microgravity in vivo and in vitro, respectively. Sprague-Dawley rats were exposed to HLS for 6 weeks to induced bone loss and simultaneously administrated with hydrogen water (HW). Then, we investigated the effects of incubation with hydrogen-rich medium (HRM) on MC3T3-E1 and RAW264.7 cells exposed to modeled microgravity. Treatment with HW alleviated HLS-induced reduction of bone mineral density, ultimate load, stiffness, and energy in femur and lumbar vertebra. Treatment with HW alleviated HLS-induced augmentation of malondialdehyde content and peroxynitrite content and reduction of total sulfhydryl content in femur and lumbar vertebra. In cultured MC3T3-E1 cells, incubation with HRM inhibited modeled microgravity-induced ROS formation, reduction of osteoblastic differentiation, increase of ratio of receptor activator of nuclear factor kappa B ligand to osteoprotegerin, inducible nitric oxide synthetase upregulation, and Erk1/2 phosphorylation. In cultured RAW264.7, incubation with HRM aggravated modeled microgravity-induced ROS formation, osteoclastic differentiation, and osteoclastogenesis. Treatment with molecular hydrogen alleviates microgravity-induced bone loss in rats. Molecular hydrogen could thus be envisaged as a nutritional countermeasure for spaceflight but remains to be tested in humans.

Resveratrol prevents the wasting disorders of mechanical unloading by acting as a physical exercise mimetic in the rat

Long-term spaceflight induces hypokinesia and hypodynamia, which, along microgravity per se, result in a number of significant physiological alterations, such as muscle atrophy, force reduction, insulin resistance, substrate use shift from fats to carbohydrates, and bone loss. Each of these adaptations could turn to serious health deterioration during the long-term spaceflight needed for planetary exploration. We hypothesized that resveratrol (RES), a natural polyphenol, could be used as a nutritional countermeasure to prevent muscle metabolic and bone adaptations to 15 d of rat hindlimb unloading. RES treatment maintained a net protein balance, soleus muscle mass, and soleus muscle maximal force contraction. RES also fully maintained soleus mitochondrial capacity to oxidize palmitoyl-carnitine and reversed the decrease of the glutathione vs. glutathione disulfide ratio, a biomarker of oxidative stress. At the molecular level, the protein content of Sirt-1 and COXIV in soleus muscle was also preserved. RES further protected whole-body insulin sensitivity and lipid trafficking and oxidation, and this was likely associated with the maintained expression of FAT/CD36, CPT-1, and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in muscle. Finally, chronic RES supplementation maintained the bone mineral density and strength of the femur. For the first time, we report a simple countermeasure that prevents the deleterious adaptations of the major physiological functions affected by mechanical unloading. RES could thus be envisaged as a nutritional countermeasure for spaceflight but remains to be tested in humans.

Developing Techniques for Astronaut Adaptation to Short-Radius Centrifugation as a Spaceflight Countermeasure

Developing Techniques for Astronaut Adaptation to Short-Radius Centrifugation as a Spaceflight Countermeasure

Large-scale mRNA analysis of female skeletal muscles during 60 days of bed rest with and without exercise or dietary protein supplementation as countermeasures

Microgravity has a dramatic impact on human physiology, illustrated in particular, with skeletal muscle impairment. A thorough understanding of the mechanisms leading to loss of muscle mass and structural disorders is necessary for defining efficient clinical and spaceflight countermeasures. We investigated the effects of long-term bed rest on the transcriptome of soleus (SOL) and vastus lateralis (VL) muscles in healthy women (BRC group, n = 8), and the potential beneficial impact of protein supplementation (BRN group, n = 8) and of a combined resistance and aerobic training (BRE group, n = 8). Gene expression profiles were obtained using a customized microarray containing 6,681 muscles-relevant genes. A two-class statistical analysis was applied on 2,103 genes with consolidated expression in BRC, BRN, and BRE groups. We identified 472 and 207 mRNAs whose expression was modified in SOL and VL from BRC group, respectively. Further clustering analysis, identifying relevant biological mechanisms and pathways, reported five main subclusters. Three are composed of upregulated mRNAs involved mainly in nucleic acid and protein metabolism, and two made up of downregulated transcripts encoding components involved in energy metabolism. Exercise countermeasure demonstrated drastic compensatory effects, decreasing the number of differentially expressed mRNAs by 89 and 96% in SOL and VL, respectively. In contrast, nutrition countermeasure had moderate effects and decreased the number of differentially-expressed transcripts by 40 and 25% in SOL and VL. Together, these data present a systematic, global and comprehensive view of the adaptive response of female muscle to long-term atrophy.

Neuromuscular Responses to Mechanical Foot Stimulation: The Influence of Loading and Postural Context

Recent work indicates mechanical stimulation of soles may attenuate muscle atrophy initiated by gravitational unloading, including that experienced during spaceflight. The aim of the present study was to determine the modulating effect of unloading and body configurations on the neuromuscular response to mechanical foot stimulation. A solenoid (2.5-cm2 surface area) embedded within a platform provided non-noxious stimulation to the lateral foot sole: 100 ms duration, 3-mm protrusion. Stimulation was applied while measuring root mean square electromyography of the soleus and lateral gastrocnemius. Experiment 1 compared seated and standing conditions, as well as different levels of gravitational unloading created by suspension. Experiment 2 altered postural stability by varying leg stance widths during a static stepping posture. Either the foot of the support leg or the nonsupport leg was stimulated. Reduced levels of loading further altered the level of postural challenge and support while maintaining the same body configuration. In both experiments, loading was not a modulating factor to the response, supporting the use of mechanical foot pressure as a countermeasure for spaceflight. Body configuration and postural instability both modulated the response, independently of load. In conclusion, an application of dynamic foot stimulation could be used to elicit neuromuscular activity without the need of background muscle activity or gravitational loading. However, the body configuration of the user with respect to postural stability needs to be considered in the application, and may provide further scope of benefits extending to the activation of postural synergies.

Seventh Symposium on the Role of the Vestibular Organs in Space Exploration Noordwijk, The Netherlands, June 7–9, 2006

The Seventh Symposium on the Role of the Vestibular Organs in Space Exploration was held at the European Space Technology Centre (ESTEC), in Noordwijk, The Netherlands, on June 7–9, 2006. The host for this conference was the European Space Agency (ESA). The conference was co-sponsored by the National Aeronautics and Space Administration (NASA) and the National Space Biomedical Research Institute (NSBRI). There have been six previous NASA-sponsored symposia in this series. Written proceedings of the first five symposia, held between 1965–1970 in Pensacola, Florida, are available from the NASA Technical Reports Server (http://ntrs.nasa.gov/search.jsp, and enter “Role of Vestibular Organs” as the search term). The Sixth NASA Symposium was held in Portland, Oregon in 2002. The program and abstracts from this meeting were published by the Journal of Vestibular Research as part of Volume 11 (3–5); these abstracts can be accessed through the IOS Press web site (http://iospress.metapress.com/home/main.mpx). In addition, most of the papers from the Sixth Symposium were submitted to the Journal of Vestibular Research and appear as Volume 13 (4–6). Each of the seven Symposia on the Role of the Vestibular Organs in Space Exploration address the adverse physiological effects mediated by the vestibular system in humans exposed to microgravity. A European venue was particularly appropriate for the Seventh Symposium, since the space neurovestibular field has become increasingly international. Researchers from many countries have had the opportunity to conduct experiments on the Russian Mir station, the US Space Shuttle, and the International Space Station. Symposium participants included more than one hundred scientists, flight surgeons, postdoctoral fellows and students from Europe, the US, Canada, Russia and Japan. It was an exciting three day meeting: More than 50 platform presentations and 20 posters were presented, describing results from investigations in spaceflight, parabolic flight, and ground laboratories. Session topics included the vestibulo-ocular reflex, clinical assessment of vestibular disorders, neurophysiology, spatial orientation, spaceflight countermeasures, balance and locomotion, motion sickness, otolith and semicircular canal physiology, and artificial gravity. The meeting concluded with an international panel discussion on challenges and opportunities in space research. We would like to thank the Journal of Vestibular Research for this Special Issue devoted to papers presented at this Symposium. We would also like to thank the presenters who submitted full papers, which underwent peer-review, for this special issue. The web site for the Symposium (http://www.congrex.nl/06a07/) contains the full scientific program; many of the slide presentations and posters are also available at this web site.