Exercise and Testosterone Countermeasures to Mitigate Metabolic Changes during Bed Rest.

BACKGROUND/OBJECTIVES: Exercise is a front-line countermeasure used to maintain astronaut health during long-duration spaceflight; however, reductions in metabolic health still occur. Accordingly, we evaluated serial changes in metabolic parameters in a spaceflight analog and evaluated the efficacy of exercise with or without the addition of low-dose testosterone treatment on mitigating adverse metabolic changes. SUBJECTS/METHODS: Healthy young (<55 years) men were randomly assigned to one of three groups during 70-days of strict, diet controlled, 6° head-down bed rest: Control (CON, n=9), exercise plus testosterone countermeasure (TEX, n=8), or exercise countermeasure plus placebo (PEX, n=9). Basal metabolic rate (BMR), glucose tolerance, and insulin sensitivity were measured before, during, and after bed rest. Exercise energy expenditure and excess post-exercise oxygen consumption were measured in TEX and PEX subjects during bed rest. RESULTS: Leptin decreased during bed rest (Pre to BR+0 changed from 6.9 ± 5.1, 5.8 ± 4.2, and 4.7 ± 4.1 to 7.9 ±3.6, 6.5 ± 4.6, and 4.1 ±3.0 ug• L-1 for CON, PEX, and TEX respectively). Bed rest induced a decrease in BMR (Pre to BR57 changed from 1655 ± 212, 1629 ± 108, and 1706 ± 146 to 1476 ± 166, 1668 ± 142, and 1603 ± 132 kcal • day-1 ± 95%CI for CON, PEX, and TEX respectively). Similarly, bed rest negatively affected glucose metabolism assessed by 2hr OGTT glucose (Pre to BR66 changed from 6.29 ± 0.72, 5.13 ± 0.72, and 5.87 ± 0.73 to 6.62 ± 0.72, 5.83 ± 0.72, and 7.08 ± 0.72 mmol • L-1 ± 95%CI). Reambulation following bed rest positively affected glucose tolerance in CON (2hr OGTT glucose at BR+12: 5.3 ± 0.72, 6.42 ± 0.73, and 6.04 ± 0.73 mmol • L-1 ± 95%CI). Testosterone protected against bed rest induced insulin resistance (HOMA-IR from Pre to BR+66 changed from 1.74 ± 0.54, 1.18 ± 0.55, and 1.45 ± 0.56 to 2.24 ± 0.56, 1.47 ± 0.54, and 1.07 ± 0.54). CONCLUSION: This study confirmed that inactivity during 70 days of head-down bed rest adversely affects metabolic health. The daily exercise countermeasures were beneficial but not completely protective of bed rest induced decrements in metabolic health. Supplementary countermeasures such as testosterone may provide additional benefits not provided by exercise alone.

The Behavioral Biology of Teams: Multidisciplinary Contributions to Social Dynamics in Isolated, Confined, and Extreme Environments.

Teams in isolated, confined, and extreme (ICE) environments face many risks to behavioral health, social dynamics, and team performance. Complex long-duration ICE operational settings such as spaceflight and military deployments are largely closed systems with tightly coupled components, often operating as autonomous microsocieties within isolated ecosystems. As such, all components of the system are presumed to interact and can positively or negatively influence team dynamics through direct or indirect pathways. However, modern team science frameworks rarely consider inputs to the team system from outside the social and behavioral sciences and rarely incorporate biological factors despite the brain and associated neurobiological systems as the nexus of input from the environment and necessary substrate for emergent team dynamics and performance. Here, we provide a high-level overview of several key neurobiological systems relevant to social dynamics. We then describe several key components of ICE systems that can interact with and on neurobiological systems as individual-level inputs influencing social dynamics over the team life cycle-specifically food and nutrition, exercise and physical activity, sleep/wake/work rhythms, and habitat design and layout. Finally, we identify opportunities and strategic considerations for multidisciplinary research and development. Our overarching goal is to encourage multidisciplinary expansion of team science through (1) prospective horizontal integration of variables outside the current bounds of team science as significant inputs to closed ICE team systems and (2) bidirectional vertical integration of biology as the necessary inputs and mediators of individual and team behavioral health and performance. Prospective efforts to account for the behavioral biology of teams in ICE settings through an integrated organizational neuroscience approach will enable the field of team science to better understand and support teams who work, live, serve, and explore in extreme environments.

Bridging the gap between military prolonged field care monitoring and exploration spaceflight: the compensatory reserve.

The concept of prolonged field care (PFC), or medical care applied beyond doctrinal planning timelines, is the top priority capability gap across the US Army. PFC is the idea that combat medics must be prepared to provide medical care to serious casualties in the field without the support of robust medical infrastructure or resources in the event of delayed medical evacuation. With limited resources, significant distances to travel before definitive care, and an inability to evacuate in a timely fashion, medical care during exploration spaceflight constitutes the ultimate example PFC. One of the main capability gaps for PFC in both military and spaceflight settings is the need for technologies for individualized monitoring of a patient's physiological status. A monitoring capability known as the compensatory reserve measurement (CRM) meets such a requirement. CRM is a small, portable, wearable technology that uses a machine learning and feature extraction-based algorithm to assess real-time changes in hundreds of specific features of arterial waveforms. Future development and advancement of CRM still faces engineering challenges to develop ruggedized wearable sensors that can measure waveforms for determining CRM from multiple sites on the body and account for less than optimal conditions (sweat, water, dirt, blood, movement, etc.). We show here the utility of a military wearable technology, CRM, which can be translated to space exploration.

Exercise effects on bed rest-induced brain changes.

PURPOSE: Spaceflight negatively affects sensorimotor behavior; exercise mitigates some of these effects. Head down tilt bed rest (HDBR) induces body unloading and fluid shifts, and is often used to investigate spaceflight effects. Here, we examined whether exercise mitigates effects of 70 days HDBR on the brain and if fitness and brain changes with HDBR are related. METHODS: HDBR subjects were randomized to no-exercise (n = 5) or traditional aerobic and resistance exercise (n = 5). Additionally, a flywheel exercise group was included (n = 8). Exercise protocols for exercise groups were similar in intensity, therefore these groups were pooled in statistical analyses. Pre and post-HDBR MRI (structure and structural/functional connectivity) and physical fitness measures (lower body strength, muscle cross sectional area, VO2 max, body composition) were collected. Voxel-wise permutation analyses were used to test group differences in brain changes, and their associations with fitness changes. RESULTS: Comparisons of exercisers to controls revealed that exercise led to smaller fitness deterioration with HDBR but did not affect brain volume or connectivity. Group comparisons showed that exercise modulated post-HDBR recovery of brain connectivity in somatosensory regions. Posthoc analysis showed that this was related to functional connectivity decrease with HDBR in non-exercisers but not in exercisers. Correlational analyses between fitness and brain changes showed that fitness decreases were associated with functional connectivity and volumetric increases (all r >.74), potentially reflecting compensation. Modest brain changes or even decreases in connectivity and volume were observed in subjects who maintained or showed small fitness gains. These results did not survive Bonferroni correction, but can be considered meaningful because of the large effect sizes. CONCLUSION: Exercise performed during HDBR mitigates declines in fitness and strength. Associations between fitness and brain connectivity and volume changes, although unadjusted for multiple comparisons in this small sample, suggest that supine exercise reduces compensatory HDBR-induced brain changes.

Blood Flow Restricted Exercise Compared to High Load Resistance Exercise During Unloading.

BACKGROUND: Bed rest studies have shown that high load (HL) resistance training can mitigate the loss of muscle size and strength during musculoskeletal unloading; however, not all individuals are able to perform HL resistance exercise. Blood flow restricted (BFR) resistance exercise may be a novel way to prevent maladaptation to unloading without requiring HL exercise equipment. This study evaluated the muscular training adaptations to HL and BFR resistance training during unilateral lower limb suspension (ULLS), a human limb unloading model. ULLS allows for evaluation of exercise training in both weight-bearing and nonweight-bearing legs within the same individual. METHODS: There were 13 participants who completed 25 d of ULLS and were counterbalanced to: 1) HL, N = 6; or 2) BFR, N = 7, training groups. During ULLS, HL and BFR performed unilateral leg press and heel raise exercise (3 d/wk). RESULTS: In weight-bearing legs, both HL and BFR increased knee extensor muscle cross-sectional area (CSA) and strength. In nonweight-bearing legs, knee extensor CSA and strength increased only in HL and decreased with BFR. CONCLUSION: HL and BFR resistance exercise were both effective exercise programs for the weight-bearing leg. However, BFR exercise was not as effective as HL resistance exercise in the nonweight-bearing leg. These data show that exercise that improved muscle CSA and strength in ambulatory weight-bearing conditions was not sufficient to maintain muscle function during unloading. For the preservation of muscle CSA and strength, BFR exercise should be considered an adjunct but not a primary exercise countermeasure for future space missions. Hackney KJ, Downs ME, Ploutz-Snyder L. Blood flow restricted exercise compared to high load resistance exercise during unloading. Aerosp Med Hum Perform. 2016; 87(8):688-696.

The Astronaut-Athlete: Optimizing Human Performance in Space.

It is well known that long-duration spaceflight results in deconditioning of neuromuscular and cardiovascular systems, leading to a decline in physical fitness. On reloading in gravitational environments, reduced fitness (e.g., aerobic capacity, muscular strength, and endurance) could impair human performance, mission success, and crew safety. The level of fitness necessary for the performance of routine and off-nominal terrestrial mission tasks remains an unanswered and pressing question for scientists and flight physicians. To mitigate fitness loss during spaceflight, resistance and aerobic exercise are the most effective countermeasure available to astronauts. Currently, 2.5 h·d, 6-7 d·wk is allotted in crew schedules for exercise to be performed on highly specialized hardware on the International Space Station (ISS). Exercise hardware provides up to 273 kg of loading capability for resistance exercise, treadmill speeds between 0.44 and 5.5 m·s, and cycle workloads from 0 and 350 W. Compared to ISS missions, future missions beyond low earth orbit will likely be accomplished with less vehicle volume and power allocated for exercise hardware. Concomitant factors, such as diet and age, will also affect the physiologic responses to exercise training (e.g., anabolic resistance) in the space environment. Research into the potential optimization of exercise countermeasures through use of dietary supplementation, and pharmaceuticals may assist in reducing physiological deconditioning during long-duration spaceflight and have the potential to enhance performance of occupationally related astronaut tasks (e.g., extravehicular activity, habitat construction, equipment repairs, planetary exploration, and emergency response).

Exercise as potential countermeasure for the effects of 70 days of bed rest on cognitive and sensorimotor performance.

BACKGROUND: Spaceflight has been associated with changes in gait and balance; it is unclear whether it affects cognition. Head down tilt bed rest (HDBR) is a microgravity analog that mimics cephalad fluid shifts and body unloading. In consideration of astronaut's health and mission success, we investigated the effects of HDBR on cognition and sensorimotor function. Furthermore, we investigated if exercise mitigates any cognitive and sensorimotor sequelae of spaceflight. METHOD: We conducted a 70-day six-degree HDBR study in 10 male subjects who were randomly assigned to a HDBR supine exercise or a HDBR control group. Cognitive measures (i.e., processing speed, manual dexterity, psychomotor speed, visual dependency, and 2D and 3D mental rotation) and sensorimotor performance (functional mobility (FMT) and balance performance) were collected at 12 and 8 days pre-HDBR, at 7, 50, and 70 days in HDBR, and at 8 and 12 days post-HDBR. Exercise comprised resistance training, and continuous and high-intensity interval aerobic exercise. We also repeatedly assessed an outside-of-bed rest control group to examine metric stability. RESULTS: Small practice effects were observed in the control group for some tasks; these were taken into account when analyzing effects of HDBR. No significant effects of HDBR on cognition were observed, although visual dependency during HDBR remained stable in HDBR controls whereas it decreased in HDBR exercise subjects. Furthermore, HDBR was associated with loss of FMT and standing balance performance, which were almost fully recovered 12 days post-HDBR. Aerobic and resistance exercise partially mitigated the effects of HDBR on FMT and accelerated the recovery time course post-HDBR. DISCUSSION: HDBR did not significantly affect cognitive performance but did adversely affect FMT and standing balance performance. Exercise had some protective effects on the deterioration and recovery of FMT.

Peak exercise oxygen uptake during and following long-duration spaceflight.

This investigation was designed to measure aerobic capacity (V̇o2peak) during and after long-duration International Space Station (ISS) missions. Astronauts (9 males, 5 females: 49 ± 5 yr, 77.2 ± 15.1 kg, 40.6 ± 6.4 ml·kg(-1)·min(-1) [mean ± SD]) performed peak cycle tests ∼90 days before flight, 15 days after launch, every ∼30 days in-flight, and on recovery days 1 (R + 1), R + 10, and R + 30. Expired metabolic gas fractions, ventilation, and heart rate (HR) were measured. Data were analyzed using mixed-model linear regression. The main findings of this study were that V̇o2peak decreased early in-flight (∼17%) then gradually increased during flight but never returned to preflight levels. V̇o2peak was lower on R + 1 and R + 10 than preflight but recovered by R + 30. Peak HR was not different from preflight at any time during or following flight. A sustained decrease in V̇o2peak during and/or early postflight was not a universal finding in this study, since seven astronauts were able to attain their preflight V̇o2peak levels either at some time during flight or on R + 1. Four of these astronauts performed in-flight exercise at higher intensities compared with those who experienced a decline in V̇o2peak, and three had low aerobic capacities before flight. These data indicate that, while V̇o2peak may be difficult to maintain during long-duration ISS missions, aerobic deconditioning is not an inevitable consequence of long-duration spaceflight.

Acute vascular and cardiovascular responses to blood flow-restricted exercise.

UNLABELLED: Blood flow-restricted resistance exercise improves muscle strength; however, the cardiovascular response is not well understood. PURPOSE: This investigation measured local vascular responses, tissue oxygen saturation (StO2), and cardiovascular responses during supine unilateral leg press and heel raise exercise in four conditions: high load with no occlusion cuff, low load with no occlusion cuff, and low load with occlusion cuff pressure set at 1.3 times resting diastolic blood pressure (BFRDBP) or at 1.3 times resting systolic blood pressure (BFRSBP). METHODS: Subjects (N = 13) (men/women, 5/8, 31.8 ± 12.5 yr, 68.3 ± 12.1 kg, mean ± SD) performed three sets of leg press and heel raise to fatigue with 90-s rest. Artery diameter, velocity time integral, and stroke volume were measured using two-dimensional and Doppler ultrasound at rest and immediately after exercise. HR was monitored using a three-lead ECG. Finger blood pressure was acquired by photoplethysmography. Vastus lateralis StO2 was measured using near-infrared spectroscopy. A repeated-measures ANOVA was used to analyze exercise work and StO2. Multilevel modeling was used to evaluate the effect of exercise condition on vascular and cardiovascular variables. Statistical significance was set a priori at P < 0.05. RESULTS: Artery diameter did not change from baseline during any of the exercise conditions. Blood flow increased after exercise in each condition except BFRSBP. StO2 decreased during exercise and recovered to baseline levels during rest only in low load with no occlusion cuff and high load with no occlusion cuff. HR, stroke volume, and cardiac output (Q˙) responses to exercise were blunted in blood flow-restricted exercise. Blood pressure was elevated during rest intervals in blood flow-restricted exercise. CONCLUSIONS: Our results demonstrate that cuff pressure alters the hemodynamic responses to resistance exercise. These findings warrant further evaluations in individuals presenting cardiovascular risk factors.