Unloading observed during spaceflight or strict bed rest induces rapid and dramatic declines in aerobic fitness and muscular strength. Peak aerobic capacity (V˙O2peak), lower body muscle cross-sectional area (CSA), and strength are decreased by approximately 10%–15% after short-duration (∼14 d) spaceflight and simulated microgravity exposure (i.e., bed rest) (2,10,11,36). Daily aerobic and resistance exercise are performed on missions to the International Space Station (ISS) to maintain physical fitness. Historically, these exercise programs have not been fully effective for the protection of crewmember aerobic fitness and muscular strength (13,24). The spaceflight exercise equipment itself was recently improved (2009–2010) and now can facilitate exercise intensities that may be reasonably expected to preserve fitness during long-duration space missions. There is considerable variability among recent crewmembers with respect to postflight fitness, with some crewmembers experiencing no losses whatsoever and others with 30% decrements in V˙O2peak or muscle strength ([13,24], and unpublished observations). In an effort to optimize in-flight exercise prescriptions and better understand the complex relationship between strict unloading and high-intensity exercise, a series of ISS flight and ground-based bed rest studies are underway.
Studies of healthy ambulatory individuals suggest that high-load resistance exercise and high-intensity interval aerobic training most effectively increase muscle strength and aerobic fitness, respectively (32,35). Astronauts are required to perform both resistance and aerobic training. However, because there are known incompatibilities between concurrent resistance and aerobic training, there is a need for more research to optimize their integration (17).
Bed rest is a well-respected spaceflight analog and has been used as a platform to test various exercise modalities. For example, daily treadmill exercise performed with lower body negative pressure (LBNP) maintained peak aerobic capacity during 30 d of bed rest (20,40) and inertial flywheel resistance exercise protected thigh (but not calf) muscle CSA and strength (4). The WISE-2005 bed rest studies represent the only attempts to integrate resistance and aerobic training and showed that alternating days of flywheel resistance exercise and treadmill interval training within LBNP also preserved thigh muscle volume and upright aerobic capacity (measured 3 d after bed rest) during 60 d of bed rest (28). The WISE studies provide optimism that short bouts of daily exercise can indeed overcome the dramatic unloading experienced in bed rest. Unfortunately, the unique exercise equipment used in these studies (LBNP + treadmill and flywheel based resistance exercise) is not available on the ISS. It has been suggested that LBNP or other forms of “artificial gravity” will be absolutely required to maintain fitness during long duration spaceflights (16). Alternatively, maintenance of muscular and aerobic fitness with exercise alone has not been previously demonstrated, and it is unknown whether it is even possible to fully maintain fitness without any form of gravity (LBNP, centrifugation, etc.).
We aspired to mimic the ISS exercise equipment capability during long-duration bed rest to develop an ISS-compatible spaceflight exercise analog. The bed rest analog provides for a far more rapid, inexpensive, and controlled experimental environment to optimize exercise programs for eventual use in spaceflight. In preparation for a long-duration bed rest study, we evaluated an integrated resistance and high-intensity aerobic training (iRAT) exercise program during 14 d of bed rest using horizontal exercise devices comparable to the equipment available on the ISS. The protocol includes supine resistance exercises for the lower body, vertical treadmill running, and supine cycle ergometry. This suite of exercise hardware allows for an exercise variety and intensity that is similar to that available to ISS astronauts. The purpose of this study was 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.
Nine healthy individuals (eight men and one woman) completed the study (age = 34 ± 8 yr, body mass = 76 ± 10 kg, stature = 177 ± 6 cm, BMI = 24 ± 2 kg·m−2, V˙O2peak = 2.0 ± 0.8 L·min−1 or 37 ± 11 mL·kg−1·min−1). They were recruited and screened in two phases according to standard National Aeronautic and Space Administration (NASA) Flight Analog Project procedures. In phase 1, potential subjects were prescreened using an application found online or via telephone interviews by the Test Subject Screening Facility nursing staff. Candidates who met the basic inclusion criteria were asked to complete a second application, which included a log of their daily physical activity, consent for a background check, health history questionnaire, and a NASA-modified Air Force Class III physical examination. This physical included a thorough examination by a medical doctor, a vision and hearing screening, a complete blood and urine analysis, an electrocardiogram, a drug and alcohol screening, and infectious disease screening. In addition to the standard NASA bed rest exclusion criteria detailed by Meck et al. (23), subjects with a history of musculoskeletal injury that could affect exercise performance or expose the subject to an increased risk of injury were excluded from the study. In phase 2 of the screening process, qualified study candidates performed an upright peak cycle ergometry test and an isokinetic knee extension test with the speed set at 60°·s−1. Minimum levels of cardiorespiratory fitness (V˙O2peak > 30 mL·kg−1·min−1) and lower body muscle strength relative to body mass (knee extension > 2.0 N·m·kg−1) were required to enter the study. These criteria were established to recruit subjects that were generally similar in fitness to the astronaut core. More specifically, the intent was to exclude the most unfit and sedentary subjects and to inform guidelines for future longer-duration bed rest studies with respect to initial fitness required to successfully complete an intense bed rest training program. All subjects gave their written informed consent to the experimental conditions after being given a detailed explanation of the study and tour of the Flight Analogs Research Unit (FARU). The study was approved by both the NASA and University of Texas Medical Branch institutional review boards.
The study was conducted at the NASA FARU at the University of Texas Medical Branch in Galveston, TX. After 2–3 wk of dietary acclimation and familiarization with the exercise hardware and study procedures, subjects were confined to 14 d of horizontal bed rest. The horizontal position was maintained at all times. A controlled diet was provided (55% carbohydrate, 30% fat, and 15% protein). Measurements of V˙O2peak, isokinetic testing around the knee and ankle joints, isometric leg press strength, and isotonic leg press power and endurance were obtained before and after bed rest. Magnetic resonance imaging (MRI) scans of the upper and lower leg were obtained before, during, and after bed rest and were evaluated for muscle CSA. Data on adherence to the prescribed exercise intensity and subjective assessments of comfort and acceptability of exercise were noted. There was no traditional control group consisting of individuals subjected to bed rest and no exercise. The rationale for this decision were as follows: (a) it is well documented that 14 d of strict bed rest or unloading induces declines in aerobic and musculoskeletal fitness both in our bed rest facility (5) and others (40); (b) it is already known that exercise is better than “no exercise” for preserving fitness during unloading, therefore, showing that iRAT is associated with greater fitness than “no exercise” would not be a significant contribution; and (c) because of the considerable expense associated with bed rest and the novelty of the exercise program, we felt the best and most ethical use of available resources was nine exercise subjects as opposed to two groups of four or five subjects.
Subjects reported to the FARU 21 d before the scheduled start of bed rest. During this acclimation period, subjects were familiarized with the exercise equipment and performed pre–bed rest training on the equipment 5 d·wk−1. Resistance exercises were performed under light load with a focus on the proper form for each exercise. All aerobic interval sessions were completed on the Stand-alone Zero-gravity Locomotion Simulator (sZLS) vertical treadmill with subjects loaded to 75% of body weight. After 2 wk, subjects were evaluated on supine resistance exercise form and the ability to perform aerobic exercise at the prescribed intensity. Those who passed this assessment were entered into the bed rest phase of the study; others were allowed one additional week for further familiarization.
Subjects followed the standard FARU horizontal bed rest procedures previously detailed by Meck et al. (23). Briefly, this included strict compliance with the horizontal position at all times, standard wake/sleep schedule where lights were on at 0600 and off at 2200, and a 3-meal-per-day controlled diet with energy intake adjusted to maintain body weight within 1 kg of pre–bed rest body weight. Subjects were cared for by a nursing staff that made daily measurements of body weight, blood pressure, and HR before breakfast. A physician also examined the subjects daily. During bed rest, subject compliance was monitored 24 h·d−1 by closed-circuit cameras. Toileting, showering, and all activities were performed in the supine position.
iRAT exercise training
During 14 d of horizontal bed rest, subjects exercised 6 d·wk−1 (3 d of resistance and 6 d of aerobic exercise). Supine aerobic exercise was performed using the sZLS vertical treadmill (Fig. 1A), and supine cycle ergometer and resistance exercise were performed on the horizontal exercise fixture (HEF) (Fig. 1B). High-intensity interval aerobic exercise and continuous aerobic exercise were performed on alternating days. Resistance exercise was performed 3 d·wk−1 on the same day as the continuous aerobic exercise, separated by 4–6 h. In a typical week, resistance and continuous exercises were performed on days 1, 3, and 5; interval exercise was performed on days 2, 4, and 6; and no exercise was performed on day 7. This protocol was developed using an evidence-based approach that included literature reviews and subject matter experts representing both exercise science and spaceflight operations. The literature review focused on the identification of effective training programs for skeletal muscle, bone, and cardiovascular health. The best aspects of each training program were combined into an integrated training program that was reviewed and endorsed by science experts. Finally, the program was modified to become operational and endorsed by ISS implementation experts.
The aerobic exercise intensities were prescribed as a percentage of V˙O2peak and HRpeak achieved during the pre–bed rest upright peak cycle test. Continuous exercise intensity was targeted at 80% of V˙O2peak. For the interval days, one of three interval protocols were performed: 1) 6 × 2-min stages at target intensities of 70%, 80%, 90%, 100%, 90%, and 80% of V˙O2peak with a 2-min rest; 2) 8 × 30-s at maximal effort with a 15-s active rest; 3) 4 × 4 min at a target intensity of 85% V˙O2peak with a 3-min active rest. Each interval was performed once per week. HR was monitored continuously during training sessions. Treadmill speed and cycle ergometer load (W) were adjusted by the test operators during the exercise session to meet the target HR for the continuous and interval sessions. Expired gas fractions were measured using a Parvo Medics TrueOne™ metabolic cart (Parvo Medics, Sandy, UT) during one of each of the interval protocols and continuous exercise sessions to verify that subjects achieved the appropriate intensity. Oxygen consumption (V˙O2) and carbon dioxide production (V˙CO2), rate of ventilation (V˙E), and RER were averaged in 15-s increments during exercise. The metabolic data obtained during the working phases of the 4- and 2-min intervals and over the entire exercise session for the 30-s interval and continuous sessions were used to evaluate exercise intensity.
Resistance exercise sessions consisted of three sets of 12 repetitions on each of four lifts (supine squat, supine leg press, supine heel raise, and prone lying leg curl). During the first six sessions of pre–bed rest training, study personnel determined 10 repetition maximums (RMs) for each exercise (6). In subsequent sessions, loads were selected based on the estimated 10-RM load and the repetitions completed during the third (final) set from the previous session. Subjects were instructed to continue until volitional fatigue on the third set of each exercise. If the subject completed more than the prescribed number of repetitions in the third set, the load was increased accordingly for the next session. If a subject could not successfully complete the prescribed repetitions, the load was maintained or decreased accordingly for the next session. Load and total repetitions performed were used to quantify the work performed for weeks 1 and 2 of bed rest. Total repetitions each week were calculated as the sum of the repetitions performed during the week, weekly load was calculated as the sum of the weight lifted for each type of exercise performed during the week, and total work was calculated as the sum of the repetitions × load for each exercise set performed during the week.
Aerobic fitness was assessed during peak upright cycle ergometry tests (Lode Excalibur Sport; Lode B.V., Groningen, the Netherlands) performed twice before (screening, BR − 14) and twice after bed rest (BR + 0, BR + 5). The protocol consisted of a 3-min warm-up at 50 W, followed by 25-W increases each minute. The female subject started at 45 W, and the workload was increased 15 W·min−1. Tests were terminated at volitional fatigue. HR and rhythm were monitored continuously (Q-Stress ECG monitor; Quinton Instruments, Seattle, WA). Expired gases were collected continuously and analyzed using a Parvo Medics TrueOne™ metabolic cart. Expired gas fractions (V˙O2, V˙CO2, V˙E, and RER) were averaged in 30-s increments. HRpeak was reported as the highest rate recorded on the ECG. Oxygen consumption was also measured during exercise training to assess the metabolic cost of the different protocols. Exercise energy expenditure and excess postexercise oxygen consumption were collected once for each exercise protocol during bed rest (total = five sessions per subject). Before the start of each exercise session, subjects were fitted with an HR monitor (Polar 810i; Polar USA Inc., Montvale, NJ) and a facemask connected to the metabolic cart. Baseline metabolic rate was established during a 10- min preexercise rest period with the subject resting supine. Metabolic data were collected throughout the exercise. For resistance exercise, the metabolic cart was rolled along with subjects as they moved from one weight machine to another. When the exercise session was complete, subjects rested for 30 min while recovery metabolic data were collected. Exercise energy expenditure was calculated from the average exercise V˙O2 and RER. Excess postexercise oxygen consumption was calculated using a computer software program (MATLAB for Windows, V4.2c0.1; The MathWorks, Inc., 1994) that averaged V˙O2, V˙E, HR, and RER in 5-min increments.
Ventilatory threshold (VT) was estimated from the data obtained during each peak cycle test. Computerized modeling using a specially written MATLAB program was used as the primary method of assessing VT, and visual inspection was used if the computerized approach produced unreasonable results. The computerized modeling and visual identification methods were compared previously by our laboratory in 20 data sets where both approaches were acceptable and agreed within 5%. The computerized modeling estimated VT by the V-slope method, using a simple iterative approach, similar to those previously reported by Orr et al. (25), Beaver et al. (8), and Gaskill et al. (14). Following the approaches in Jones et al. (18) and Lundberg et al. (21), the data were modeled as:
For each data set, V˙O2 and V˙CO2 time series were truncated by removing the first 2 min of warm-up and all data samples obtained after the V˙O2peak. All plots were visually inspected for an obvious second VT breakpoint; however, a second breakpoint was not identified for any of the tests. The model was then fit to a set of VT candidate points obtained by sequentially (sample by sample) varying VT over its full range of possible values. The estimated VT was determined as the VT candidate point that minimized the mean square error of the overall fit.
Visual identification of VT was performed on tests that resulted in an unreasonable VT value using the computerized modeling. Visual determinations were made by two independent technicians using the ventilatory equivalents or V-slope method (14). If the VT values were not different by more than 3% between technicians, the average was used as the VT; if values differed by more than 3%, a third technician evaluated the test; if the VT value from the third technician was within 3% of the one of the other technicians, the average value was used as the VT; if the third technician’s VT value was not within 3% of the values determined by the other technicians, the test was deemed as indeterminate.
Isokinetic force–velocity spectrum
Knee flexor/extensor and ankle plantar/dorsiflexion strength were tested using a Biodex System 4 dynamometer (Biodex Medical Systems Inc., Shirley, NY) twice before (BR − 19 and BR − 12) and after bed rest (BR + 2 and BR + 9). Knee and ankle tests were all performed on the right leg. To test knee flexion/extension strength, subjects were seated with the hip angle at 90° and the thigh securely strapped to the seat. To test ankle plantar/dorsiflexion strength, subjects lay prone with their foot securely attached to a foot plate. The test speeds used for the knee extensors/flexors were 0°·s−1, 60°·s−1, 120°·s−1, 180°·s−1, 300°·s−1, and 400°·s−1. Knee strength–endurance was also evaluated from the total work performed over 20 maximal repetitions at 180°·s−1. The plantar flexors and extensors were tested at 0°·s−1, 30°·s−1, 60°·s−1, 120°·s−1, 180°·s−1, 300°·s−1, and 400°·s−1. In addition, eccentric strength was tested at 30°·s−1. After a 5-min warm-up on a cycle ergometer at 50 W, subjects performed three to five warm-up repetitions at 50% of maximal effort before the data collection. During the test trials, subjects were encouraged to give maximal efforts throughout the range of motion. For the knee endurance test, subjects were instructed to perform each repetition maximally and not to pace themselves. The peak torque obtained at each speed was used for data analyses.
Leg press testing
Isometric strength and dynamic power were assessed using a specially designed leg press twice before bed rest (BR − 16 and BR − 10) and once after bed rest (BR + 1). Isometric strength testing was performed using a customized 35° leg press machine (6000a Leg Press; Nebula Fitness Equipment, Versailles, OH) equipped with a force plate, position transducer, and magnetic braking system (Fitness Technology, Skye, SA, Australia). During the maximal isometric force (MIF) test, the footplate position was adjusted to elicit a knee angle of 90°, which was determined by manual measurement with a goniometer. Knee angle and foot placement were also standardized across testing sessions. The footplate was fixed in place using mechanical stops to permit isometric force development. Force was measured by a force plate attached to the foot plate of the leg press. As a warm-up, subjects completed two submaximal efforts (approximately 50% and 75% of perceived maximum effort) for 5 s each, with 30 s of rest in between each effort. Thereafter, subjects performed three maximal efforts for 5 s with 30 s of rest between each effort. If the two highest MIF values differed by more than 5%, then a fourth trial was conducted. Subjects were instructed to reach maximal effort as quickly as possible with no countermovement to quantify the rate of force development (RFD).
To assess dynamic power, subjects performed 21 consecutive ballistic, concentric-only bilateral leg press actions beginning at a knee angle of 90°. Subjects were instructed to extend their legs through a full range of motion, “throwing” the load away from the body as forcefully and quickly as possible. The external load was fixed at 40% of the measured MIF, which has previously been shown to elicit maximal power output (33). A magnetic brake (Fitness Technology) was used to catch the weight as soon as the sled reached its peak height so that no eccentric muscle actions were performed. After each repetition, the sled was lowered quickly and passively to the starting position. Time between repetitions was ∼2 s. Velocity, force, and power were calculated for each repetition. Fatigue index and total work were also calculated. Fatigue index was defined as the decline in power production from the repetition eliciting the highest power (usually within first 2–3 repetitions and always within the first 10 repetitions) to the repetition eliciting the lowest power (always within the last 10 repetitions) divided by the highest power.
MRI acquisition and analysis
Axial spin-echo T2-weighted MRI images were acquired from the level of the ankle mortise to the iliac crest while subjects lay supine in a 1.5-T scanner (Signa Horizon LX; General Electric, Fairfield, CT). Images of the thigh and lower leg were generated using a repetition time of 2000 ms, echo time of 51 ms, slice thickness of 10 mm, and a gap between slices of 10 mm. A matrix size of 512 × 512 was used for all scans, and the field of view was varied to maximize in-plane resolution for each scan. All MRI images were transferred to personal computers, and muscles were manually traced using Image-J (version 1.42; National Institutes of Health, Bethesda, MD) (1). The reliability of this technique in our laboratory has been previously reported (29). The area of the gap between slices was interpolated by averaging the slices analyzed before and after the gap. Muscle CSA was defined as the average of all analyzed and interpolated slices. The CSA of the knee extensor (KE) muscle group was determined from the rectus femoris (RF) and the pooled CSA of the vastus lateralis, vastus intermedius, and vastus medialis (VASTI). The CSA of the knee flexor (KF) muscle group was determined from the grouped biceps femoris (short and long heads), semitendinosus, and semimembranosis. The CSA of the adductor (ADD) muscle group was determined from the grouped adductor magnus, adductor longus, and adductor brevis. The CSA of the plantar flexor (PF) muscle group was determined from the sum of the medial gastrocnemius (MG), lateral gastrocnemius (LG), and soleus (SOL), which were individually analyzed. Skeletal muscle, subcutaneous (SAT), and intermuscular adipose tissue (IMAT) were measured volumetrically using MIPAV software (version 4.3.1; Medical Image Processing, Analysis and Visualization, Center for Information Technology, National Institutes of Health). One subject was not evaluated with MIPAV analysis because of motion artifact. IMAT was defined as the visible high-signal- intensity (light) pixels between muscle groups and within muscle fascia when bone and subcutaneous adipose tissue were removed. Subcutaneous adipose tissue was defined by the same parameters previously described (22); however, skin, muscle, bone, and IMAT were removed. For both analyses, a well-established nonparametric non–uniform intensity normalization (N3) algorithm was used to correct smoothly varying shading caused by poor radiofrequency coil uniformity or gradient-driven eddy currents (22,31). The intratester reliability of identifying the signal intensity threshold was 0.038% (coefficient variability), similar to previously reported variability (22).
All data are presented as means ± SE. Repeated-measures ANOVA were conducted to evaluate differences over time in each of the dependent variables. If a significant time effect was detected, post hoc comparisons were made using Bonferroni test. All statistical analyses were performed with SPSS 17.0 for Windows. The level of significance was set at P < 0.05.
Exercise Training Sessions
Eleven subjects were admitted into the study and nine subjects (one woman and eight men) completed the study (mean ± SD: age = 34.5 ± 8.2 yr, height = 177.1 ± 5.5 cm, weight = 74.7 ± 10.5 kg, V˙O2peak = 36.8 ± 16.6 mL·kg−1·min−1, knee extensor strength = 2.5 ± 0.5 N·m·kg−1). Two subjects were dismissed in the pre–bed rest phase: one subject was unable to complete the exercise prescription because of aerobic fitness limitations. This particular subject’s screening V˙O2peak was very close to the minimum threshold and suggests that 30 mL·kg−1·min−1 may indeed represent the lower level of aerobic fitness required for participation. One subject was dismissed because of health concerns unrelated to the investigation. Of the nine subjects who completed the study, four subjects required 2 wk of pre–bed rest training and five subjects required 3 wk of pre–bed rest training to learn the proper supine form and/or reach a level of comfort adequate to complete the training program. Because only 1 of 11 potential subjects was unable to complete the exercise program after 3 wk, we concluded that 3 wk of pretraining, and our minimum fitness values for V˙O2peak and knee extension strength are appropriate for future studies of this exercise program.
Subject exercise compliance was high. Most subjects completed all of the 18 exercise sessions (6 aerobic continuous, 6 aerobic interval, and 6 resistance) as scheduled during bed rest. One subject did not perform leg press exercise because of low back pain during the exercise and instead performed four sets of each of the other exercise, one subject missed a continuous exercise session because of knee pain that subsided after rest and ice, and one subject missed a resistance exercise session because of low back pain that subsided the next day. All interval aerobic exercise sessions were performed on the sZLS, and most continuous aerobic exercise sessions were performed on the supine cycle ergometer. This high level of compliance is important to note and demonstrates that it is possible to train recreationally active subjects at very high intensity during bed rest.
HR and metabolic data collected during the interval and continuous aerobic sessions provide evidence that exercise was performed at the targeted intensities (Table 1). However, there was a high degree of variability in interval and continuous aerobic exercise intensity among individuals (%V˙O2peak range: 30-s interval = 83%–99%; 2-min interval = 69%–110%; 4-min interval = 70%–116%; continuous = 64%–81%). The treadmill speed and/or body weight loading were increased as tolerated from the first to second week of interval sessions in all but one subject who maintained speed and load from week 1 to week 2. Six of the subjects performed treadmill exercise with 75%–85% body weight loading and three subjects exercised at 90%–100% body weight loading. Subjects also performed the iRAT resistance exercise as prescribed and were able to perform exercises at a higher load the second week compared to the first week of bed rest. In general, subjects performed fewer repetitions at a higher load for each exercise during week 2 compared to week 1; however, the target number of repetitions (432) was obtained each week (Table 1). Each exercise session required approximately 200–400 kcal. Interestingly, the shortest exercise bout (30-s intervals) required on average 300 kcal per session because of the high intensity of the effort (Table 1).
V˙O2peak and VT
Aerobic fitness increased from the screening test to BR − 14 and was maintained from before to after bed rest (Table 2). HRpeak and RER were not different between testing days (185 ± 4 bpm and 1.20 ± 0.03), indicating that subject effort was similar between tests. A VT was identified for all subjects on the screening, BR − 14, and BR + 5 testing days; however, the VT was indeterminate for one subject on BR + 0. For subjects (n = 8) with an identified VT on all testing days, VT was maintained from BR − 14 to BR + 0 (BR − 14 = 1.93 ± 0.17 L·min−1 and BR + 0 = 2.03 ± 0.21 L·min−1).
Isokinetic force–velocity spectrum
Knee extension and flexion peak torque were maintained from before to after bed rest at isokinetic velocities of 60°·s−1, 180°·s−1, 300°·s−1, and 400°·s−1 (Fig. 2). At 120°·s−1, knee extension and flexion peak torque were higher on BR + 2 compared to BR − 19 (P = 0.049 and P = 0.020, respectively). Although not statistically significant, mean knee extension and flexion total work increased from BR − 19 to BR + 2 (before vs after bed rest, percent change: extension = 2086 ± 117 vs 2286 ± 146 N·m, 9.6%; flexion = 1504 ± 57 vs 1651 ± 108 N·m, 9.7%). Ankle plantar and dorsiflexion were not different at any isokinetic velocity from before to after bed rest.
Muscle strength, RFD, and power–endurance
Leg press MIF, RFD, maximum power, total work, and fatigue index are shown in Table 3. Overall, MIF (P = 0.33) and RFD (P = 0.08) did not change significantly from the first and second pre–bed rest tests to post–bed rest test; however, RFD after bed rest was 6% and 10% lower than the first and second pre–bed rest tests, respectively. Leg press maximum power was higher after bed rest compared to the first pre–bed rest test (P = 0.01). Leg press total work did not change from the first and second pre–bed rest tests to post–bed rest test (P = 0.12). Although not statistically significant (P = 0.30), fatigue index was lower after bed rest compared to the first pre–bed rest (3.5%) and second pre–bed rest (14%) tests.
Muscle CSA and volume
Muscle CSA of individual muscles and muscle groups are shown in Table 4. The CSA of the VASTI muscles increased significantly during and after bed rest compared to before bed rest (P = 0.03), which facilitated a trend (P = 0.09) toward enhanced CSA in the knee extensors. There were no significant changes across time for any other muscles or muscle groups. The volume of subcutaneous adipose tissue, intramuscular adipose tissue, or total muscle did not change over 14 d of bed rest.
This study evaluated the combined effects of daily, high-intensity supine aerobic and resistance training on aerobic fitness and muscle function, as well as the feasibility of implementing a high-intensity exercise prescription during 14 d of bed rest. We showed that aerobic fitness and maximal leg power increased from before to after bed rest, and muscle strength and endurance were maintained from before to after bed rest. In addition, we demonstrated that the exercise prescription can be implemented within the scheduling constraints of a bed rest study with multiple investigators with high subject compliance and without injury, which indicates it could be feasibly implemented in longer-duration bed rest studies and spaceflight. These results suggest that adherence to the iRAT prescription could improve or at least maintain astronauts’ ability to perform mission-related tasks such as emergency egress and extravehicular activity by protecting both cardiorespiratory fitness and muscle performance. This is the first report of a complete preservation of aerobic and muscular fitness during 14 d of bed rest using exercise alone. These data demonstrate, for the first time, that it is possible to alleviate the deleterious effects of strict bed rest for 2 wk with approximately 1 h of exercise per day. It is important to know that once- or twice-daily exercise sessions can compensate for the drastic unloading observed during strict bed rest. It is likely that the intensity of the exercise was a major contributor to the success of the program.
Many other previous bed rest studies have provided the supporting evidence used to develop the present exercise program. For example, studies using an aerobic exercise training countermeasure have shown that upright V˙O2peak is well protected during bed rest with multiple daily bouts (90 min accumulated) of moderate-intensity (75% pre–bed rest HRpeak) supine cycling (30) and three to five weekly ∼30-min bouts of treadmill interval exercise performed with LBNP (20,40). It appears that moderate-intensity bouts of lower body exercise (70%–80% 1-RM) can attenuate losses in aerobic capacity (15,34), whereas high-load protocols have been most effective in protecting against muscle mass, strength, and power losses in the knee extensor and plantar flexors (4,9,39). The WISE-2005 bed rest study also implemented a combined aerobic and resistance training protocol, in which subjects performed treadmill interval exercise (intensity range = 40%–80% V˙O2peak) with LBNP 2–4 d·wk−1 and supine leg press and plantarflexion resistance exercise (maximal effort for 7–14 reps) every third day using an inertial flywheel for 60 d. The WISE prescription statistically preserved peak upright aerobic capacity (−8.3% measured 3 d after bed rest) (28) but lacked measurements of ventilatory/anaerobic threshold and immediate post–bed rest data. The WISE program was also able to maintain thigh muscle volume and contractility and attenuate atrophy of the plantar flexors (39).
In the present investigation, we showed increase or maintained aerobic fitness (V˙O2peak and VT) and muscle performance (strength, power, and endurance) measured immediately after bed rest. Furthermore, CSA of the upper and lower leg was maintained from before to after bed rest. We have expanded on the current body of literature by evaluating variables associated with aerobic fitness and muscle strength that are not frequently reported in disuse studies. First, we demonstrated that VT is maintained throughout 14 d of bed rest, which is particularly important with regard to extravehicular activity task readiness. To our knowledge, VT has not been evaluated in a bed rest exercise training study. However, it is known that VT is dramatically reduced after even very short bouts of unloading as Convertino et al. (11) reported a 25% reduction in VT and a 7% reduction in V˙O2peak after only 10 d of head-down-tilt bed rest. While they are certainly related, the work of Convertino et al. suggests that VT is more adversely affected with bed rest than V˙O2peak. Submaximal work capacity is essential to the performance of occupational and functional tasks, and thus, decrements in VT may have more impact on occupational performance than losses in peak aerobic capacity.
The iRAT protocol maintained muscle CSA and strength of the knee extensors and plantar flexors after 14 d of bed rest. There is considerable evidence in the literature that unloading in the absence of any countermeasure induces significant muscle atrophy and loss of function. For example, after only 1 wk of unloading, whole muscle CSA of the knee extensors declined ∼3% (12), and after 2 wk, myofibril CSA was reduced by 16% (5). In addition, a 12% reduction in the isokinetic strength was reported after 16 d of unilateral lower limb suspension (3). In comparison, our study did not observe significant changes in either isometric knee extension (−5.0%) or the isokinetic knee extension peak torque across velocities of 60°·s−1, 180°·s−1, 300°·s−1, and 400°·s−1. Interestingly, improvements at 120°·s−1 in both knee extension and flexion were noted in this study, which may reflect the specificity of the velocity that most closely characterized the exercise countermeasure training. In this capacity, leg press MIF, which was tested in a position similar to the supine leg press exercise training, showed small (nonsignificant) improvement (+3.0%) following bed rest.
The protection of plantar flexor muscle strength and size is particularly novel as these muscles are notoriously difficult to maintain during spaceflight and simulated microgravity. The soleus, in particular, is highly plastic and, to date, has been challenging to protect (37,38). Soleus muscle size was maintained (−1.4%) in the present investigation. It is not possible to systematically determine which aspect of the exercise program provided the greatest contribution to the training adaptations of the lower leg; however, it is plausibly due to the combination of the high-speed treadmill running and heel raise. A longer-duration bed rest study will be needed to determine whether the iRAT protocol can maintain plantar flexor muscle strength and size beyond the 14-d period used in this investigation.
One of the most intriguing findings of this study was the improvement in leg press muscle power (3.9%). A previous bed rest study assessed muscle power during a stair climb test and showed a 14% decline after only 10 d of bed rest (19). Lower extremity power is important to protect because it is predictive of the ability to perform functional tasks in young and middle-age adults and activities of daily living in older adults (7). Given that deconditioning during prolonged unloading may reflect similar adaptations as aging (losses in muscle strength and size and neuromuscular impairment), enhanced leg press power after an unloading period could be important for astronaut task performance such as emergency egress or injury mitigation upon return to a gravitational environment. The corresponding 2.0% increase in VASTI CSA after bed rest is likely to have facilitated the improvement in muscle power; however, other enhancements (increased muscle fiber shortening velocity, neurological function, tendon elasticity, and ATP-PCr levels) could have played a role in this adaptation.
Collectively, the iRAT exercise prescription clearly demonstrates the potential benefit of high-load resistance exercise coupled with high-intensity interval training using conventional equipment in a spaceflight analog. On the basis of the experience gained in this study, it also appears that it is possible for recreationally active participants to successfully perform this high-intensity exercise during bed rest without undue fatigue or injury.
Compatibility of resistance and aerobic training
Ground-based compatibility studies suggest that, after an initial phase of improved fitness, an interference exists between aerobic and resistance training such that the gains achieved after a combined program are less than those achieved via aerobic or strength training alone, particularly when aerobic and resistance sessions are completed on the same day as opposed to alternate days (17). Other investigators have demonstrated that multiple daily bouts of moderate- to high-load resistance exercise and high-intensity interval aerobic training may be an efficient means to protect muscle strength (4,5), bone health (26,27), and cardiovascular fitness (15,20,35) during unloading; however, to date, the interference has not been specifically studied in unloaded environments. Although we did not seek to parcel out the independent effects of aerobic and resistance exercise, our results indicate that it is possible to maintain both aerobic and muscular fitness using a concurrent resistance and aerobic program during bed rest. It is likely important that our resistance and aerobic exercise sessions were always separated by four or more hours.
This study is the first to evaluate the efficacy of an exercise prescription that uses a suite of exercise hardware similar to that currently available to astronauts onboard the ISS. This is the first report that exercise alone, in the absence of any form of artificial gravity, can preserve cardiorespiratory and muscular fitness despite 14 d of strict unloading. We demonstrated improvements in V˙O2peak, muscle power, and hypertrophy of the VASTI muscles. A long-duration bed rest study with a more robust study design and measurements to fully evaluate aerobic fitness muscle size and strength and bone health throughout bed rest is a logical next step toward evaluating the potential of using high-intensity exercise alone as an effective countermeasure during long-duration spaceflight.
Exercise is Medicine®
EIM is an American College of Sports Medicine initiative to “make physical activity and exercise a standard part of a disease prevention and treatment medical paradigm.” While this program is designed for implementation in the community, much of the research published in Medicine & Science in Sports & Exercise ® directly or indirectly supports the mission of EIM. The research described in this article highlights the importance of exercise from a unique perspective. Strict bed rest is a potent stimulus for deconditioning, not only in controlled research subjects such as this study but even more importantly for those hospitalized for medical purposes. Hospital-associated deconditioning and functional decline are common problems with a paucity of research or clinical recommendation examining prevention, functional recovery, or reconditioning. The current study illustrates the unique capability of exercise alone to prevent deconditioning associated with strict bed rest. Subjects spent <1 h·d−1, with some days as little as 15 min, performing exercise and were able to preserve muscle size, strength, and aerobic capacity during 14 d of strict bed rest in which they were not allowed to sit up even for a moment. All toileting, showering, eating, and personal hygiene were performed while lying in a hospital bed. While this is a dramatic experimental paradigm to induce deconditioning, it provides a unique context to clearly illustrate the potent effect of exercise as medicine. No other form of treatment including any known drug has such the capability to prevent deconditioning and maintain functional capacity.
The authors thank the research participants who provided considerable feedback on implementation logistics as well as Drs. Richard Simpson and William Paloski from the University of Houston for development of the MATLAB program to identify ventilatory threshold. The authors would also like to thank the entire staff of the Exercise Physiology and Countermeasures Lab and the Flight Analogs Project at Johnson Space Center for the implementation of the study. This work was funded by NASA’s Human Research Program.
The authors do not have any professional relationships with companies or manufacturers who will benefit from the results of the present study.
The results of the present study do not constitute endorsement by the American College of Sports Medicine.
1. Abramoff MD, Magelhaes PJ, Ram SJ. Image processing with ImageJ. Biophot Intl
. 2004; 11: 36–42.
2. Adams GR, Caiozzo VJ, Baldwin KM. Skeletal muscle unweighting: spaceflight
and ground-based models. J Appl Physiol
. 2003; 95 (6): 2185–201.
3. Adams GR, Hather BM, Dudley GA. Effect of short-term unweighting on human skeletal muscle strength and size. Aviat Space Environ Med
. 1994; 65 (12): 1116–21.
4. Alkner BA, Tesch PA. Knee extensor and plantar flexor muscle size and function following 90 days of bed rest with or without resistance exercise. Eur J Appl Physiol
. 2004; 93 (3): 294–305.
5. Bamman MM, Clarke MS, Feeback DL, et al. Impact of resistance exercise during bed rest on skeletal muscle sarcopenia and myosin isoform distribution. J Appl Physiol
. 1998; 84 (1): 157–63.
6. Beachle TR, Earle RW, Wathen D. Resistance training
. In: Essentials of Strength Training and Conditioning
. Champaign (IL): Human Kinetics; 2008. p. 392–400.
7. Bean JF, Kiely DK, Herman S, et al. The relationship between leg power and physical performance in mobility-limited older people. J Am Geriatr Soc
. 2002; 50 (3): 461–7.
8. Beaver WL, Wasserman K, Whipp BJ. A new method for detecting anaerobic threshold by gas exchange. J Appl Physiol
. 1986; 60 (6): 2020–7.
9. Brooks N, Cloutier GJ, Cadena SM, et al. Resistance training
and timed essential amino acids protect against the loss of muscle mass and strength during 28 days of bed rest and energy deficit. J Appl Physiol
. 2008; 105 (1): 241–8.
10. Convertino V, Hung J, Goldwater D, DeBusk RF. Cardiovascular responses to exercise in middle-aged men after 10 days of bedrest. Circulation
. 1982; 65 (1): 134–40.
11. Convertino VA, Karst GM, Kirby CR, Goldwater DJ. Effect of simulated weightlessness on exercise-induced anaerobic threshold. Aviat Space Environ Med
. 1986; 57 (4): 325–31.
12. Ferrando AA, Tipton KD, Bamman MM, Wolfe RR. Resistance exercise maintains skeletal muscle protein synthesis during bed rest. J Appl Physiol
. 1997; 82 (3): 807–10.
13. Fitts RH, Trappe SW, Costill DL, et al. Prolonged space flight–induced alterations in the structure and function of human skeletal muscle fibres. J Physiol
. 2010; 588 (Pt 18): 3567–92.
14. Gaskill SE, Ruby BC, Walker AJ, Sanchez OA, Serfass RC, Leon AS. Validity and reliability of combining three methods to determine ventilatory threshold. Med Sci Sports Exerc
. 2001; 33 (11): 1841–8.
15. Greenleaf JE, Bernauer EM, Ertl AC, Trowbridge TS, Wade CE. Work capacity during 30 days of bed rest with isotonic and isokinetic exercise training
. J Appl Physiol
. 1989; 67 (5): 1820–6.
16. Hargens AR, Bhattacharya R, Schneider SM. Space physiology VI: exercise, artificial gravity, and countermeasure development for prolonged space flight. Eur J Appl Physiol.
2013; 113 (9): 2183–92.
17. Hickson RC. Interference of strength development by simultaneously training
for strength and endurance. Eur J Appl Physiol Occup Physiol
. 1980; 45 (2–3): 255–63.
18. Jones RH, Molitoris BA. A statistical method for determining the breakpoint of two lines. Anal Biochem
. 1984; 141 (1): 287–90.
19. Kortebein P, Symons TB, Ferrando A, et al. Functional impact of 10 days of bed rest in healthy older adults. J Gerontol A Biol Sci Med Sci
. 2008; 63 (10): 1076–81.
20. Lee SM, Schneider SM, Boda WL, et al. Supine LBNP exercise maintains exercise capacity in male twins during 30-d bed rest. Med Sci Sports Exerc
. 2007; 39 (8): 1315–26.
21. Lundberg MA, Hughson RL, Weisiger KH, Jones RH, Swanson GD. Computerized estimation of lactate threshold. Comput Biomed Res
. 1986; 19 (5): 481–6.
22. Manini TM, Clark BC, Nalls MA, Goodpaster BH, Ploutz-Snyder LL, Harris TB. Reduced physical activity increases intermuscular adipose tissue in healthy young adults. Am J Clin Nutr
. 2007; 85 (2): 337–84.
23. Meck JV, Dreyer SA, Warren LE. Long-duration head-down bed rest: project overview, vital signs, and fluid balance. Aviat Space Environ Med
. 2009; 80 (5 Suppl): A1–8.
24. Moore ADJ, Lee SMC, Everett ME, Guined JR, Knudsen P. Aerobic capacity following long duration International Space Station (ISS) Missions: preliminary results. In: 82nd Annual Scientific Meeting of the Aerospace Medicine Association. Vol. 82
. Anchorage (AK): Aviation Space and Environmental Medicine; 2011. p. 345–46.
25. Orr GW, Green HJ, Hughson RL, Bennett GW. A computer linear regression model to determine ventilatory anaerobic threshold. J Appl Physiol
. 1982; 52 (5): 1349–52.
26. Robling AG, Burr DB, Turner CH. Partitioning a daily mechanical stimulus into discrete loading bouts improves the osteogenic response to loading. J Bone Miner Res
. 2000; 15 (8): 1596–602.
27. Rubin CT, Lanyon LE. Regulation of bone mass by mechanical strain magnitude. Calcif Tissue Int
. 1985; 37 (4): 411–7.
28. Schneider SM, Lee SM, Macias BR, Watenpaugh DE, Hargens AR. WISE-2005: exercise and nutrition countermeasures
for upright V˙O2peak
during bed rest. Med Sci Sports Exerc
. 2009; 41 (12): 2165–76.
29. Scott J, Martin D, Cunningham D, et al. Reliability and validity of ultrasound cross-sectional area measurements for long-duration spaceflight
. Med Sci Sports Exerc
. 2011; 43 (5): 823–4.
30. Shibasaki M, Wilson TE, Cui J, Levine BD, Crandall CG. Exercise throughout 6 degrees head-down tilt bed rest preserves thermoregulatory responses. J Appl Physiol
. 2003; 95 (5): 1817–23.
31. Sled JG, Zijdenbos AP, Evans AC. A nonparametric method for automatic correction of intensity nonuniformity in MRI data. IEEE Trans Med Imaging
. 1998; 17 (1): 87–97.
32. Spiering BA, Kraemer WJ, Anderson JM, et al. Resistance exercise biology: manipulation of resistance exercise programme variables determines the responses of cellular and molecular signalling pathways. Sports Med
. 2008; 38 (7): 527–40.
33. Spiering BA, Lee SM, Mulavara AP, et al. Test battery designed to quickly and safely assess diverse indices of neuromuscular function after unweighting. J Strength Cond Res
. 2011; 25 (2): 545–55.
34. Stremel RW, Convertino VA, Bernauer EM, Greenleaf JE. Cardiorespiratory deconditioning
with static and dynamic leg exercise during bed rest. J Appl Physiol
. 1976; 41 (6): 905–9.
35. Tabata I, Nishimura K, Kouzaki M, et al. Effects of moderate-intensity endurance and high-intensity intermittent training
on anaerobic capacity and V˙O2max
. Med Sci Sports Exerc
. 1996; 28 (10): 1327–30.
36. Tesch PA, Berg HE, Bring D, Evans HJ, LeBlanc AD. Effects of 17-day spaceflight
on knee extensor muscle function and size. Eur J Appl Physiol
. 2005; 93 (4): 463–68.
37. Trappe S, Costill D, Gallagher P, et al. Exercise in space: human skeletal muscle after 6 months aboard the International Space Station. J Appl Physiol
. 2009; 106 (4): 1159–68.
38. Trappe S, Creer A, Minchev K, et al. Human soleus single muscle fiber function with exercise or nutrition countermeasures
during 60 days of bed rest. Am J Physiol Regul Integr Comp Physiol
. 2008; 294 (3): R939–47.
39. Trappe TA, Burd NA, Louis ES, Lee GA, Trappe SW. Influence of concurrent exercise or nutrition countermeasures
on thigh and calf muscle size and function during 60 days of bed rest in women. Acta Physiol (Oxf)
. 2007; 191 (2): 147–59.
40. Watenpaugh DE, Ballard RE, Schneider SM, et al. Supine lower body negative pressure exercise during bed rest maintains upright exercise capacity. J Appl Physiol
. 2000; 89 (1): 218–27.