Disuse-Induced Muscle Loss and Rehabilitation: The National Aeronautics and Space Administration Bed Rest Study.

OBJECTIVES: The time course and magnitude of atrophic remodeling and the effects of an acute rehabilitation program on muscle atrophy are unclear. We sought to characterize bed rest-induced leg muscle atrophy and evaluate the safety and efficacy of an acute rehabilitation program. DESIGN: Prespecified analysis of a randomized controlled trial. SETTING: Single-center urban hospital. PATIENTS: Adults (24-55 yr) randomized to 70 days of sedentary bed rest. INTERVENTIONS: The 11-day post-bed rest rehabilitation program consisted of low intensity exercise and progressed to increased aerobic exercise duration, plyometric exercises, and higher intensity resistance exercise. MEASUREMENTS AND MAIN RESULTS: Upper (rectus femoris, vastus lateralis, quadriceps, hamstrings, adductors) and lower leg (medial gastrocnemius, lateral gastrocnemius, and soleus) MRI scans were obtained once before, nine times during, and three times after bed rest to assess muscle cross-sectional area. The magnitude and rate of muscle atrophy and recovery were determined for each muscle. Nine participants completed 70 days of sedentary bed rest and an 11-day rehabilitation program. A total of 11,588 muscle cross-sectional area images were quantified. Across all muscles except the rectus femoris (no change), there was a linear decline during bed rest, with the highest atrophic rate occurring in the soleus (-0.33%/d). Following rehabilitation, there was rapid recovery in all muscles; however, the quadriceps (-3.74 cm2; 95% CI, -7.36 to -0.12; p = 0.04), hamstrings (-2.30 cm2; 95% CI, -4.07 to -0.54; p = 0.01), medial gastrocnemius (-0.62 cm2; 95% CI, -1.10 to -0.14; p = 0.01), and soleus (-1.85 cm2; 95% CI, -2.90 to -0.81; p < 0.01) remained significantly lower than baseline. CONCLUSIONS: Bed rest results in upper and lower leg muscle atrophy in a linear pattern, and an 11-day rehabilitation program was safe and effective in initiating a rapid trajectory of muscle recovery. These findings provide important information regarding the design and refinement of rehabilitation programs following bed rest.

High intensity training during spaceflight: results from the NASA Sprint Study.

Historically, International Space Station (ISS) exercise countermeasures have not fully protected astronauts' musculoskeletal and cardiorespiratory fitness. Although these losses have been reduced on more recent missions, decreasing the time required to perform in-flight exercise would permit reallocation of that time to other tasks. To evaluate the effectiveness of a new training prescription, ISS crewmembers performed either the high intensity/lower volume integrated Sprint resistance (3 d wk-1) and aerobic (interval and continuous workouts, each 3 d wk-1 in alternating fashion) exercise program (n = 9: 8M/1F, 48 ± 7 y, 178 ± 5 cm, 77.7 ± 12.0 kg) or the standard ISS countermeasure consisting of daily resistance and aerobic exercise (n = 17: 14M/3F, 46 ± 6 y, 176 ± 6 cm, 80.6 ± 10.5 kg) during long-duration spaceflight. Bone mineral density (dual energy X-ray absorptiometry (DXA)), muscle strength (isokinetic dynamometry), muscle function (cone agility test), and cardiorespiratory fitness (VO2peak) were assessed pre- and postflight. Mixed-effects modeling was used to analyze dependent measures with alpha set at P < 0.05. After spaceflight, femoral neck bone mineral density (-1.7%), knee extensor peak torque (-5.8%), cone agility test time (+7.4%), and VO2peak (-6.1%) were decreased in both groups (simple main effects of time, all P < 0.05) with a few group × time interaction effects detected for which Sprint experienced either attenuated or no loss compared to control. Although physiologic outcomes were not appreciably different between the two exercise programs, to conserve time and optimally prepare crewmembers for the performance of physically demanding mission tasks, high intensity/lower volume training should be an indispensable component of spaceflight exercise countermeasure prescriptions.

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.

Exercise Countermeasures to Neuromuscular Deconditioning in Spaceflight.

The mechanical unloading of spaceflight elicits a host of physiological adaptations including reductions in muscle mass, muscle strength, and muscle function and alterations in central interpretation of visual, vestibular, and proprioceptive information. Upon return to a terrestrial, gravitational environment, these result in reduced function and performance, the potential consequences of which will be exacerbated during exploration missions to austere and distant destinations such as the moon and Mars. Exercise is a potent countermeasure to unloading-induced physiological maladaptations and has been employed since the early days of spaceflight. In-flight exercise hardware has evolved from rudimentary and largely ineffective devices to the current suite onboard the International Space Station (ISS) comprised of a cycle ergometer, treadmill, and resistance exercise device; these contemporary devices have either fully protected or significantly attenuated neuromuscular degradation in spaceflight. However, unlike current microgravity operations on the ISS, future exploration missions will include surface operations in partial gravity environments, which will require greater physiological capacity and work output of their crews. For these flights, it is critical to identify physiological thresholds below which task performance will be impaired and to develop exercise countermeasures-both pre- and in-flight-to ensure that crewmembers are able to safely and effectively complete physically demanding mission objectives. © 2020 American Physiological Society. Compr Physiol 10:171-196, 2020.

A novel approach for establishing fitness standards for occupational task performance.

PURPOSE: To identify strength and performance thresholds below which task performance is impaired. METHODS: A new weighted suit system was used to manipulate strength-to-body-weight ratio during the performance of simulated space explorations tasks. Statistical models were used to evaluate various measures of muscle strength and performance on their ability to predict the probability that subjects could complete the tasks in an acceptable amount of time. Thresholds were defined as the point of greatest change in probability per change in the predictor variable. For each task, median time was used to define the boundary between "acceptable" and "unacceptable" completion times. RESULTS: Fitness thresholds for four space explorations tasks were identified using 23 physiological input variables. Area under receiver operator characteristic curves varied from a low of 0.68 to a high of 0.92. CONCLUSION: An experimental analog for altering strength-to-body weight combined with a probability-based statistical model for success was suitable for identifying thresholds for task performance below which tasks could either not be completed or time to completion was unacceptably high. These results provide data for strength recommendations for exploration mission ambulatory task performance. Furthermore, the approach can be used to identify thresholds for other areas where occupationally relevant tasks vary considerably.

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.

Efficacy of Testosterone plus NASA Exercise Countermeasures during Head-Down Bed Rest.

INTRODUCTION: Prolonged confinement to head-down bed rest (HDBR) results in musculoskeletal losses similar to those observed during long-duration space flight. Exercise countermeasures by themselves have not completely prevented the deleterious losses in muscle mass or function in HDBR or space flight. PURPOSE: The objective was to investigate the safety and efficacy of intermittent, low-dose testosterone treatment in conjunction with NASA exercise (SPRINT) countermeasures during 70 d of 6° HDBR. METHODS: Healthy men (35 ± 8 yr) were randomized into one of three groups that remained inactive (CON) or performed exercise 6 d·wk in addition to receiving either placebo (PEX) or testosterone treatment (TEX, 100 mg·wk). Testosterone/placebo injections were administered once a week for 2 wk, followed by 2 wk off and so on, during HDBR. RESULTS: Total, leg, and trunk lean body mass (LBM) consistently decreased in CON, increased in TEX, and had little or no changes in PEX. Total, leg, and trunk fat mass consistently increased in CON and PEX and decreased in TEX. Leg strength decreased in CON, whereas PEX and TEX were protected against loss in strength. Changes in leg LBM correlated positively with changes in leg muscle strength. CONCLUSIONS: Addition of a testosterone countermeasure enhanced the preventative actions of exercise against body composition changes during long-term HDBR in healthy eugonadal men. This is the first report to demonstrate that cycled, low-dose testosterone treatment increases LBM under conditions of strict exercise control. These results are clinically relevant to the development of safe and effective therapies against muscle atrophy during long-term bed rest, aging, and disease where loss of muscle mass and strength is a risk. The potential space flight applications of such countermeasure combinations deserve further investigations.

Exercise Training Mitigates Multisystem Deconditioning during Bed Rest.

INTRODUCTION: This study investigated the safety and effectiveness of a new integrated aerobic and resistance exercise training prescription (SPRINT) using two different sets of exercise equipment: a suite of large International Space Station-like exercise equipment similar to what is found on the International Space Station and a single device with aerobic and resistance exercise capability in the spaceflight analog of bed rest (BR). METHODS: Subjects (n = 34) completed 70 d of 6° head down tilt BR: 9 were randomized to remain sedentary (CONT), 9 to exercise training using traditional equipment (EX), 8 to exercise using traditional equipment and low-dose testosterone supplementation (ExT), and 8 to exercise using a combined resistance and aerobic flywheel device. Peak aerobic capacity, ventilatory threshold, cardiac morphology and function (echocardiography), muscle mass (magnetic resonance imaging) and strength/power (isokinetic, leg press, and vertical jump), and bone health (bone mineral density, blood and urine bone markers) were assessed before and after BR. RESULTS: The SPRINT protocol mitigated BR-induced muscle and cardiac deconditioning regardless of the exercise device used. Molecular markers of bone did not change in the CONT or EX groups. Peak aerobic capacity was maintained from pre- to post-BR in all exercise groups similarly, whereas significant declines were observed in the CONT group (~10%). Significant interaction effects between the CONT group and all EX groups were observed for muscle performance including leg press total work, isokinetic upper and lower leg strength, vertical jump power, and maximal jump height as well as muscle size. CONCLUSIONS: This is the first trial to evaluate multisystem deconditioning and the role of an integrated exercise countermeasure. These findings have important implications for the design and implementation of exercise-based countermeasures on future long-duration spaceflight missions.

Physiological and Functional Alterations after Spaceflight and Bed Rest.

INTRODUCTION: Exposure to microgravity causes alterations in multiple physiological systems, potentially impacting the ability of astronauts to perform critical mission tasks. The goal of this study was to determine the effects of spaceflight on functional task performance and to identify the key physiological factors contributing to their deficits. METHODS: A test battery comprised of seven functional tests and 15 physiological measures was used to investigate the sensorimotor, cardiovascular, and neuromuscular adaptations to spaceflight. Astronauts were tested before and after 6-month spaceflights. Subjects were also tested before and after 70 d of 6° head-down bed rest, a spaceflight analog, to examine the role of axial body unloading on the spaceflight results. These subjects included control and exercise groups to examine the effects of exercise during bed rest. RESULTS: Spaceflight subjects showed the greatest decrement in performance during functional tasks that required the greatest demand for dynamic control of postural equilibrium which was paralleled by similar decrements in sensorimotor tests that assessed postural and dynamic gait control. Other changes included reduced lower limb muscle performance and increased HR to maintain blood pressure. Exercise performed during bed rest prevented detrimental change in neuromuscular and cardiovascular function; however, both bed rest groups experienced functional and balance deficits similar to spaceflight subjects. CONCLUSION: Bed rest data indicate that body support unloading experienced during spaceflight contributes to postflight postural control dysfunction. Further, the bed rest results in the exercise group of subjects confirm that resistance and aerobic exercises performed during spaceflight can play an integral role in maintaining neuromuscular and cardiovascular functions, which can help in reducing decrements in functional performance. These results indicate that a countermeasure to mitigate postflight postural control dysfunction is required to maintain functional performance.

Efficacy of Exercise and Testosterone to Mitigate Atrophic Cardiovascular Remodeling.

PURPOSE: Early and consistent evaluation of cardiac morphology and function throughout an atrophic stimulus is critically important for the design and optimization of interventions. This randomized controlled trial was designed 1) to characterize the time course of unloading-induced morphofunctional remodeling and 2) to examine the effects of exercise with and without low-dose testosterone supplementation on cardiac biomarker, structural, and functional parameters during unloading. METHODS: Twenty-six subjects completed 70 d of head-down tilt bed rest (BR): 9 were randomized to exercise training (Ex), 8 to EX and low-dose testosterone (ExT), and 9 remained sedentary (CONT). Exercise consisted of high-intensity, continuous, and resistance exercise. Cardiac morphology (left ventricular mass [LVM]) and mechanics (longitudinal, radial, and circumferential strain and twist), cardiovascular biomarkers, and cardiorespiratory fitness (V˙O2peak) were assessed before, during, and after BR. RESULTS: Sedentary BR resulted in a progressive decline in LVM, longitudinal, radial, and circumferential strain in CONT, whereas Ex and ExT mitigated decreases in LVM and function. Twist was increased throughout BR in sedentary BR, whereas after an initial increase at BR7, there were no further changes in twist in Ex and ExT. HDL cholesterol was significantly decreased in all groups compared with pre-BR (P < 0.007). There were no significant changes in other cardiovascular biomarkers. Change in twist was significantly related to change in V˙O2max (R = 0.68, P < 0.01). CONCLUSION: An integrated approach with evaluation of cardiac morphology, mechanics, V˙O2peak, and biomarkers provides extensive phenotyping of cardiovascular atrophic remodeling. Exercise training and exercise training with low-dose testosterone supplementation abrogates atrophic remodeling.

Isometric Midthigh Pull Reliability and Relationship to Deadlift One Repetition Maximum.

De Witt, JK, English, KL, Crowell, JB, Kalogera, KL, Guilliams, ME, Nieschwitz, BE, Hanson, AM, and Ploutz-Snyder, LL. Isometric midthigh pull reliability and relationship to deadlift one repetition maximum. J Strength Cond Res 32(2): 528-533, 2018-The purpose of this investigation was to examine the reliability of the isometric midthigh pull (IMTP) and the relationship between IMTP peak force and deadlift 1 repetition maximum (1RM). Nine subjects (5 men and 4 women; 40.6 ± 8.0 years; 1.72 ± 0.10 m; 75.6 ± 13.4 kg) participated in this study. Isometric midthigh pull and deadlift 1RM were both performed during 2 testing sessions. For IMTP, peak force and peak rate of force development (RFD) were determined, in addition to RFD at 30 ms, 50 ms, 90 ms, 150 ms, 200 ms, and 250 ms after initiation of the pull. Intraclass correlation coefficients (ICCs) were calculated to evaluate the reliability of IMTP measures. Pearson product-moment correlations and linear regression were used to determine associations between IMTP and deadlift 1RM. Isometric midthigh pull peak force was reproducible both within (ICC = 0.98 and 0.97) and between sessions (ICC = 0.89) and significantly correlated with deadlift 1RM (r = 0.88, p ≤ 0.05), but intermediate force outputs and RFD were not. Lack of associations between RFD and deadlift 1RM indicate that the ability to create explosive force may be independent of the ability to create maximal force. The strong relationship between IMTP peak force and deadlift 1RM was present regardless of which IMTP repetition across the 2 sessions was examined. Peak force generated during IMTP is a reliable method to assess full body maximal strength. A single IMTP repetition, provided adequate familiarization and warm-up, correlates strongly with deadlift 1RM. Practitioners can use the IMTP test as a method to estimate maximal deadlift strength in a quick and potentially less provocative manner than traditional 1RM testing.

Isokinetic Strength Changes Following Long-Duration Spaceflight on the ISS.

INTRODUCTION: Long-duration spaceflight results in a loss of muscle strength that poses both operational and medical risks, particularly during emergency egress, upon return to Earth, and during future extraterrestrial exploration. Isokinetic testing of the knee, ankle, and trunk quantifies movement-specific strength changes following spaceflight and offers insight into the effectiveness of in-flight exercise countermeasures. METHODS: We retrospectively evaluated changes in isokinetic strength for 37 ISS crewmembers (Expeditions 1-25) following 163 ± 38 d (mean ± SD) of spaceflight. Gender, in-flight resistance exercise hardware, and preflight strength were examined as potential modifiers of spaceflight-induced strength changes. RESULTS: Mean isokinetic strength declined 8-17% following spaceflight. One month after return to Earth, strength had improved, but small deficits of 1-9% persisted. Spaceflight-induced strength losses were not different between men and women. Mean strength losses were as much as 7% less in crewmembers who flew after the Advanced Resistive Exercise Device (ARED) replaced the interim Resistive Exercise Device (iRED) as the primary in-flight resistance exercise hardware, although these differences were not statistically significant. Absolute and relative preflight strength were moderately correlated (r = -0.47 and -0.54, respectively) with postflight strength changes. DISCUSSION: In-flight resistance exercise did not prevent decreased isokinetic strength after long-duration spaceflight. However, continued utilization of ARED, a more robust resistance exercise device providing higher loads than iRED, may result in greater benefits as exercise prescriptions are optimized. With reconditioning upon return to Earth, strength is largely recovered within 30 d.

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).

Ground reaction forces during treadmill running in microgravity.

Astronauts perform treadmill exercise during long-duration space missions to counter the harmful effects of microgravity exposure upon bone, muscle, and cardiopulmonary health. When exercising in microgravity, astronauts wear a harness and bungee system that provides forces that maintain attachment to the treadmill. Typical applied forces are less than body weight. The decreased gravity-replacement force could result in differences in ground-reaction force at a given running speed when compared to those achieved in normal gravity, which could influence the adaptive response to the performed exercise. Seven astronauts (6 m/1 f) who completed approximately 6-month missions on the International Space Station (ISS) completed a preflight (1G) and multiple in-flight (0G) data collection sessions. Ground-reaction forces were measured during running at speeds of 8.0 kph and greater on an instrumented treadmill in the lab and on the ISS. Ground-reaction forces in 0G were less than in 1G for a given speed depending upon the gravity-replacement force, but did increase with increased speed and gravity-replacement force. Ground-reaction forces attained in 1G during slower running could be attained by increasing running speed and/or increasing gravity-replacement forces in 0G. Loading rates in 1G, however, could not be replicated in 0G. While current gravity-replacement force devices are limited in load delivery magnitude, we recommend increasing running speeds to increase the mechanical loads applied to the musculoskeletal system during 0G treadmill exercise, and to potentially increase exercise session efficiency.

Bungee force level, stiffness, and variation during treadmill locomotion in simulated microgravity.

INTRODUCTION: Crewmembers performing treadmill exercise on the International Space Station must wear a harness with an external gravity replacement force that is created by elastomer bungees. The quantification of the total external force, displacement, stiffness, and force variation is important for understanding the forces applied to the crewmember during typical exercise. METHODS: Data were collected during static trials in the laboratory from a single subject and four subjects were tested while walking at 1.34 m x s(-1) and running at 2.24 m x s(-1) and 3.13 m x s(-1) on a treadmill during simulated microgravity in parabolic flight. The external force was provided by bungees and carabiner clips in configurations commonly used by crewmembers. Total external force, displacement, and force variation in the bungee system were measured, from which stiffness was computed. RESULTS: Mean external force ranged from 431 to 804 N (54-131% bodyweight) across subjects and conditions. Mean displacement was 4 to 8 cm depending upon gait speed. Mean stiffness was affected by bungee configuration and ranged from 1.73 to 29.20 N x cm(-1). Force variation for single bungee configurations was 2.61-4.48% of total external force and between 4.30-57.5% total external force for two-bungee configurations. CONCLUSIONS: The external force supplied to crewmembers by elastomer bungees provided a range of loading levels with variations that occur throughout the gait cycle. The quantification of bungee-loading characteristics is important to better define the system currently used by crewmembers during exercise.

Neuromuscular function following muscular unloading and blood flow restricted exercise.

PURPOSE: The aim of the study is to evaluate central and peripheral neuromuscular function in the knee extensors (KE) and plantar flexors (PF) after 30 days of unilateral lower limb suspension (ULLS) and to examine the effects of low-load blood flow restricted (BFR) resistance training on the KE during ULLS. METHODS: Strength, cross-sectional area (CSA), central activation, evoked force, and rates of force development and relaxation were assessed in the KE and PF before and after ULLS in sixteen subjects (9 M, 7F; 18-49 years). Eight of those subjects participated in BFR on the KE three times per week during ULLS (ULLS + Exercise). RESULTS: The ULLS group had decrements in strength and CSA of the KE (16 and 7 %, respectively) and PF (27 and 8 %, respectively) and the ULLS + Exercise maintained strength and CSA of the KE (P > 0.05), but significantly lost strength and CSA in the PF (21 and 5 %; P > 0.05). KE central activation declined 6 % in the ULLS group and was maintained in the ULLS + Exercise group, but a time × group interaction was not evident (P = 0.31). PF central activation was reduced in both groups (ULLS: -7.6 ± 9.9 and -7.9 ±11.6 %; time main effect P = 0.01). A time × group interaction for KE-evoked twitch force (P = 0.04) demonstrated a 9 % decline in the ULLS + Exercise group following the intervention. Evoked PF doublet torque decreased 12 % in both groups (P = 0.002). CONCLUSION: Central and peripheral neuromuscular function is compromised during unloading. While BFR resistance training on the KE during unloading can maintain muscle mass and strength, it may only partially attenuate neuromuscular dysfunction.

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.

Integrated resistance and aerobic exercise protects fitness during bed rest.

INTRODUCTION: The current exercise countermeasures have not fully protected astronauts' preflight aerobic and muscular fitness levels during International Space Station (ISS) missions, prompting a need to optimize the exercise prescription to improve or maintain astronauts' ability to perform critical tasks and eventually extend the duration of missions. PURPOSE: To test the hypothesis that an integrated resistance and aerobic exercise prescription performed with exercise equipment similar to that on the ISS can be tolerated and maintain cardiovascular and muscular fitness during 14 d of exposure to a model of microgravity. METHODS: Subjects (n = 9) participated in 14-21 d of pre-bed rest training and familiarization, 14 d of bed rest + iRAT exercise, and 7 d of ambulatory recovery. Peak aerobic capacity (V˙O2peak), ventilatory threshold (VT), and isokinetic and leg press tests were performed before and after bed rest to evaluate cardiovascular and muscle functions. Muscle cross-sectional area (CSA) was determined before, during, and after bed rest using magnetic resonance imaging (MRI). RESULTS: Improvements from before to after bed rest were observed in V˙O2peak (2.8 ± 0.2 to 3.2 ± 0.2 L·min(-1)), VT (1.9 ± 0.2 to 2.1 ± 0.2 L·min(-1)), leg muscle power (1582 ± 317 to 1740 ± 359 W), and muscle CSA of the grouped vastus lateralis, vastus intermedius, and vastus medialis muscles (67.5 ± 8.4 to 68.9 ± 8.3 cm). Muscle strength and total CSA of the upper and lower legs were not different from before to after bed rest. CONCLUSIONS: This is the first report of exercise being completely effective for the prevention of cardiovascular and skeletal muscle deconditioning during strict bed rest using exercise equipment similar to that on the ISS. This was accomplished with high subject compliance.

Sildenafil increases muscle protein synthesis and reduces muscle fatigue.

Reductions in skeletal muscle function occur during the course of healthy aging as well as with bed rest or diverse diseases such as cancer, muscular dystrophy, and heart failure. However, there are no accepted pharmacologic therapies to improve impaired skeletal muscle function. Nitric oxide may influence skeletal muscle function through effects on excitation-contraction coupling, myofibrillar function, perfusion, and metabolism. Here we show that augmentation of nitric oxide-cyclic guanosine monophosphate signaling by short-term daily administration of the phosphodiesterase 5 inhibitor sildenafil increases protein synthesis, alters protein expression and nitrosylation, and reduces fatigue in human skeletal muscle. These findings suggest that phosphodiesterase 5 inhibitors represent viable pharmacologic interventions to improve muscle function.

Influence of muscle strength to weight ratio on functional task performance.

Existing models of muscle deconditioning such as bed rest are expensive and time-consuming. We propose a new model utilizing a weighted suit to manipulate muscle strength, power, or endurance relative to body weight. The aims of the study were to determine as to which muscle measures best predict functional task performance and to determine muscle performance thresholds below which task performance is impaired. Twenty subjects performed seven occupational astronaut tasks (supine and upright seat egress and walk, rise from fall, hatch opening, ladder climb, object carry, and construction board activity), while wearing a suit weighted with 0-120 % of body weight. Models of the relationship between muscle function/body weight and task completion time were developed using fractional polynomial regression and verified with pre- and post-flight astronaut performance data. Spline regression was used to identify muscle function thresholds for each task. Upright seat egress and walk was the most difficult task according to the spline regression analysis thresholds. Thresholds normalized to body weight were 17.8 N/kg for leg press isometric force, 17.6 W/kg for leg press power, 78.8 J/kg for leg press work, 5.9 N/kg isometric knee extension and 1.9 Nm/kg isokinetic knee extension torque. Leg press maximal isometric force/body weight was the most reliable measure for modeling performance of ambulatory tasks. Laboratory-based manipulation of relative strength has promise as an analog for spaceflight-induced loss of muscle function. Muscle performance values normalized to body weight can be used to predict occupational task performance and to establish relevant strength thresholds.