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.

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.

Association of Exercise and Swimming Goggles With Modulation of Cerebro-ocular Hemodynamics and Pressures in a Model of Spaceflight-Associated Neuro-ocular Syndrome.

Importance: Astronauts on International Space Station missions demonstrate adverse neuro-ocular changes. Reversing a negative translaminar pressure gradient (TLPG) by modulating cerebral blood flow, decreasing intracranial pressure, or increasing intraocular pressure (IOP) has been proposed as potential intervention for spaceflight-associated neuro-ocular syndrome (SANS). Objective: To examine whether exercise (resistance, moderate-intensity aerobic, and high-intensity aerobic) or artificially increasing IOP is associated with modulated cerebro-ocular hemodynamic and pressure changes during head-down tilt (HDT), an analogue of spaceflight, in healthy adults. Design, Setting, and Participants: A single-center investigation was conducted at Johnson Space Center, Houston, Texas, from January 1, 2014, to December 31, 2016, in 20 healthy men. Exposure: On 3 separate days, participants rested supine, were tilted to -15° HDT, and then completed 1 of 3 experimental exercise conditions (moderate-intensity aerobic, resistance, or high-intensity interval aerobic). A subset of 10 participants wore swimming goggles on all days. Main Outcomes and Measures: Applanation rebound tonometry was used to noninvasively assess IOP, and compression sonography was used to assess internal jugular venous pressure (IJVP). Estimated TLPG was calculated as the difference between IOP and IJVP. Cerebral inflow and outflow were measured in extracranial arteries using color-coded duplex ultrasonography. Results: Twenty men participated in the study (mean [SD] age, 36 [9] years). Compared with supine IOP (mean [SD], 19.3 [3.7] mm Hg), IJVP (mean [SD], 21.4 [6.0] mm Hg), and estimated TLPG (mean [SD], -2.1 [7.0] mm Hg), -15° HDT was associated with increased IOP (mean difference, 2.3 mm Hg; 95% CI, 1.4-3.3 mm Hg; P < .001) and IJVP (mean difference, 10.5 mm Hg; 95% CI, 8.9-12.2 mm Hg; P < .001) and with decreased TLPG (mean difference, -8.2 mm Hg; 95% CI, -10.1 to -6.3 mm Hg; P < .001). Exercise (regardless of modality) at -15° HDT was associated with decreased IOP (mean difference, -1.6 mm Hg; 95% CI, -2.6 to -0.6 mm Hg; P = .002) and TLPG (mean difference, -3.5 mm Hg; 95% CI, -6.2 to -0.7 mm Hg; P = .01) compared with rest. Both IOP (mean difference, 2.9 mm Hg; 95% CI, 0.7-5.1 mm Hg; P = .01) and TLPG (mean difference, 5.1 mm Hg; 95% CI, 0.8-9.4 mm Hg; P = .02) were higher in participants who wore swimming goggles compared with those not wearing goggles. Conclusions and Relevance: In this study, exercise was associated with decreased IOP and estimated translaminar pressure gradient in a spaceflight analogue of HDT. The addition of swimming goggles was associated with increased IOP and TLPG in HDT. Further evaluation in spaceflight may be warranted to determine whether modestly increasing IOP is an effective SANS countermeasure.

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.

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.

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.