INTRODUCTION

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SPACEFLIGHT CAUSES SIGNIFICANT losses in total body nitrogen and muscle volume (8, 17). It is believed that these losses are at least partially responsible for the degraded muscle performance observed after spaceflight (20). During an 8-day shuttle mission, SLJ/ STS-47, the changes in volume in a number of muscle groups were determined by using pre- and postflight magnetic resonance imaging (MRI) (17). These measurements indicated a small but significant muscle-specific atrophy after only 8 days in weightlessness. Long-duration (17-wk) bed-rest studies suggest that longer missions may result in even greater muscle loss (16, 18). Therefore, these measurements were extended to longer space missions to determine whether muscle losses are linear with mission duration and to define postmission recovery rate.

Other investigators have suggested that atrophic muscle fibers are particularly susceptible to contraction-induced damage (10, 23-24). This suggests that spaceflight may render muscles susceptible to postflight injury. In fact, sore leg muscles are often reported anecdotally after short- as well as long-duration missions, with descriptions similar to delayed-onset muscle soreness. Therefore, we attempted to evaluate, in two ways, whether there may be adverse physiological changes in muscle after flight: 1) by determining early postflight swelling by using MRI volume measurements on landing day and at 2-4 days after landing, an elapsed time during which significant muscle mass recovery would not be expected, and 2) by measuring muscle transverse relaxation time (T2) of the calf muscles before and at several times after flight. Normal exercise is known to cause a transient increase in muscle T2, which resolves in <45 min (4, 5), whereas muscle damage induces T2 changes that evolve more slowly but persist for weeks (6, 14). Because it has been shown that fluid shifts associated with horizontal and head-down tilt do not change muscle T2 (3), changes in muscle T2, especially if prolonged, would indicate underlying pathology.

No study to date has reported on body composition changes after long-duration spaceflight. Of particular importance is the lean body mass (LBM) as it relates to the actual changes in regional muscle volume (from MRI) and the regional and total bone mineral content (BMC).

The specific aims of this study were to determine and compare the changes in body composition and muscle volume during flight, to determine the time course for muscle volume loss and recovery after return from space, and to assess the occurrence of early postflight muscle swelling in conjunction with postflight T2 of the calf muscles.

	METHODS

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Spacelab mission experimental design. During the Spacelab mission, 4 male crewmembers (age 43 ± 8 yr, weight 82.2 ± 8.6 kg; means ± SD) were studied. Launch and landing occurred at the Kennedy Space Center, and the mission duration was 17 days. MRI of the crewmembers was performed twice before flight at 50-51 days and 29-31 days before launch; on landing day; and 2, 10, and 30 days postflight. Except on landing day, when a portable 1.0 Tesla G.E. instrument was brought to the Kennedy Space Center landing site, MRI was accomplished by using a 1.5 Tesla Siemens machine located at Methodist Hospital in Houston.

Muscle volume. The following protocol was used for imaging the Spacelab astronauts. On landing day, to minimize changes caused by reambulation, the four crewmembers remained in wheelchairs for one to several hours after landing until imaging was complete. To minimize the effects of fluid shifts caused by changing position from standing or sitting to the recumbent position, crewmembers were recumbent for a minimum of 10-15 min before the start of data acquisition, and the order in which the measurements were made was maintained from one imaging session to next. The back was imaged first, then the thighs, and then the lower legs. This sequence allowed additional time for fluid equilibration in the lower limbs before imaging. For the lower limb imaging, the feet were positioned in a holder to minimize movement during image acquisition and to ensure repositioning. The portion of the limb being imaged was suspended while the nonimaged portion was supported with foam supports. For the thigh and calf muscles, 32 slices, 1 cm thick, were obtained by using echo time (Te) = 10 ms, repetition time = 800 ms, and a 256 × 512 matrix. For the back muscles, a similar protocol was used except that 20 slices, 0.5 cm thick, centered on the L3 vertebra, were obtained by using a spine coil (256 × 256 matrix). A calibration phantom was imaged during each session to correct for any changes in pixel size.

Muscle T2. T2 was measured by repeating the calf region scan using the same receiver gain but at a Te of 50 ms. T2 values for each muscle pixel were calculated by comparing the image intensity at Te = 10 ms and Te = 50 ms, assuming an exponential decay. Average T2 values for all muscle pixels within the calf region were computed. Because of the dependence of T2 on field strength (G.E. 1.0 Tesla vs. Siemens 1.5 Tesla), calf muscle T2 was not performed on landing day.

Shuttle/Mir experiment design. The shuttle/Mir program involved a total of seven American astronauts (six men and one woman), with a rotating Russian crew of two cosmonauts. Twelve Russian cosmonauts (all male) were crewmembers aboard the Mir space station during this time period, ten of whom agreed to participate in the MRI experiment. Of these, there were nine individuals in whom at least one pre- and one postflight MRI scan were successfully performed. The ages and weights (means ± SD) of the 16 American and Russian crewmembers were 43.7 ± 6.6 yr and 79.2 ± 6.2 kg. The mission lengths varied from 16 to 28 wk, with a mean of 23 ± 5 wk. All imaging of the American crew was done on the instrument in Houston, as described above, whereas the Russian crewmembers were scanned at the Cardiology Research Institute in Moscow, with the exception of two crewmembers, who landed at Kennedy Space Center and were scanned in Houston. The instrument at the Cardiology Research Institute was a 1.5 Tesla Siemens device and was nearly identical to the Houston machine. Calibration phantoms were used at each imaging session on each of the three machines used in this study. Pre- and postflight MRI scanning of a given crewmember, except as noted for the MRI performed on the American crew on landing day, were always performed on the same instrument.

Muscle volume and T2. The MRI acquisition protocol was the same as that used for the Spacelab mission, except that neck muscle (splenius capitis, semispinalis capitis, semispinalis cervicus, and multifidus) imaging was also included. For this purpose, 32 slices, 3 mm thick, were acquired by using a neck coil. To evaluate swelling, the change in muscle volumes between landing day and 2-4 days after landing were compared. Muscle T2 was determined as described above.

Body composition. Dual-energy X-ray absorptiometry (DEXA) scans were done once on 14 of the 16 shuttle/Mir crewmembers preflight (2 wk to 4.5 mo before launch) and postflight (3-6 days after landing, average = 5 days). The American and Russian crewmembers were scanned with the same protocol using either a Hologic 1,000-W instrument located in Star City, Russia for the Russian cosmonauts or a Hologic 1,000-W or 2,000+ (pencil beam) instrument located at the Johnson Space Center, Houston, TX.

Statistical analysis. To determine a change during spaceflight, the duplicate preflight measurements were averaged, and the data were analyzed using ANOVA for repeated measures, with a Dunnett multiple-comparison test when the ANOVA result was significant. For the total body and regional composition, a paired t-test was used to compare the pre- and postflight means. Significance was chosen as P < 0.05.

	RESULTS

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Muscle volume. The two baseline measurements for the four Spacelab flight crew were averaged, and all data points were expressed as percent change from the average baseline. The data were analyzed statistically by repeated-measures ANOVA for the five time points: preflight, landing day, and 2, 10, and 30 days after landing. Figure 1 shows the pre- and postflight average changes of the four crewmembers for each muscle group. On landing day, all regions except the hamstrings were significantly decreased compared with baseline. The largest losses (~10%) were in the ankle extensor and intrinsic back muscles, followed by the quadriceps and psoas at 5-7% and the hamstrings and anterior leg at ~3%. By 10 days after landing, no muscle groups were significantly different from baseline, although recovery appeared to be continuing for some regions.

View larger version (24K): [in this window] [in a new window]   Fig. 1.   Muscle volume loss in 4 crewmembers who spent 17 days in space aboard the shuttle Spacelab. Data are means of 4 male crewmembers for each muscle group. Data points include two preflight measurements at ~67 and 47 days before launch and three postflight measurements on landing day and at days 14 and 30.

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View larger version (27K): [in this window] [in a new window]   Fig. 2.   Muscle volume loss and recovery in 16 shuttle/Mir crewmembers who spent 4-6.5 mo in space aboard the Mir space station. Data are expressed as percentage of baseline plotted against days after landing. All 16 crewmembers received 1 or 2 scans during the first week of recovery. Twelve of the 16 received an additional scan between 12 and 22 days after recovery. Eleven of the 12 plus one other who was not scanned in the 12- to 22-day period received an additional scan at 29-84 days after recovery. An exponential function of the form Y = a + bext was used to fit the data, as indicated by the solid line in each graph. Y is the fitted percentage, a and b are fitting constants, x is the measured rate of change, and t is time after return from space.

Muscle T2 changes. Figure 3 presents the calf muscle T2 values for the four crewmembers of the 17-day Spacelab mission. ANOVA testing showed that the data at 2 and 10 days after the 17-day flight were significantly elevated compared with baseline. For the shuttle/Mir missions, missing data at the fourth and eighth week postflight precluded repeated-measures analysis for all data (Fig. 4). However, testing the baseline against the first and second week postflight measurements showed that calf muscle T2 was significantly elevated at these times.

View larger version (10K): [in this window] [in a new window]   Fig. 3.   Calf muscle transverse relaxation time (T2) values for the 4 Spacelab crewmembers (17-day mission) expressed as percent change from baseline and plotted against time after landing. Because of equipment limitations, no T2 measurements were possible on landing day; therefore, the first postflight measurements were taken 2 days after landing.

View larger version (9K): [in this window] [in a new window]   Fig. 4.   Calf muscle T2 values for 8 shuttle/Mir crewmembers (4- to 6.5-mo missions) expressed as percent change from baseline and plotted against time after landing. Because of equipment limitations, no T2 measurements were possible on landing day; therefore, the first postflight measurements were 2-4 days after landing. All 8 crewmembers were measured at 3-4 days and again at 12-17 days after flight. In 7 of the 8 crewmembers, an additional measurement was obtained at 29-84 days after flight.

Body composition. Table 2 provides the DEXA-determined whole body composition changes for the shuttle/Mir flights, showing significant losses in total mass, BMC, and LBM, but not fat. This is contrasted with body composition results reported from the 17-day mission, which showed significant loss in body weight and an equivalent loss in body fat (25). The latter is believed to be due to inadequate caloric intake. There were no changes in BMC during the shorter mission, but a significant loss of 3.4% was measured during the longer shuttle/Mir missions. Not surprisingly, bone is lost unevenly throughout the skeleton. For example, the BMC losses, as a percentage of the regional mass, were head, +0.6%; arms and ribs, 0%; thoracic spine, 0.5%; lumbar spine, 7%; pelvis, 13%; and legs, 4%. However, if the loss is presented as a fraction of the total bone that is lost (0.1 kg), we obtain the following data: head, +3%, not significant (NS); arms and ribs, 0%, NS; thoracic spine, 1%, NS; lumbar spine, 5%, P < 0.03; pelvis, 44%, P < 0.01; and legs, 53%, P < 0.01. This contrasts with the percentage of whole body bone mineral in these individuals in these same regions: head, 17%; arms, 15%; ribs, 7%; thoracic spine, 6%; lumbar spine, 2%; pelvis, 11%; and legs, 41%.

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Muscle volume. The extent and time course of muscle atrophy during spaceflight is largely unknown. Our previous study on an 8-day mission showed significant atrophy after a relatively short time and that there were differences among muscle groups (17). The present study reports on the atrophy occurring during a 17-day mission, which was one of the longest in the space shuttle program. The ankle extensor muscle volumes on the 17-day mission decreased ~11% in this study compared with ~6% after the shorter mission, suggesting a continuing loss with flight duration in these muscles. Other investigators performed pre- and postflight muscle biopsies of the soleus on these same four crewmembers (26). Postflight, muscle fibers developed less average peak force and demonstrated decreased (8%) fiber diameter, consistent with the whole muscle atrophy reported in this paper. The degree, frequency, and duration of exercise, scheduled and unscheduled, during flight will have a major impact on preservation of muscle in microgravity. In addition, the caloric intake during flight could also impact the rate and degree of muscle atrophy during flight independent of the disuse from microgravity. In the case of the 17-day mission, this could be particularly important because both body weight and fat loss were significant. As opposed to the shorter shuttle missions, all long-duration missions aboard the Mir have incorporated an extensive exercise program that has continued for all the shuttle/Mir missions reported here (20). This exercise countermeasure program appears to show efficacy. For example, the 17-day mission showed decreases up to ~10%, whereas the 4- to 6.5-mo missions showed maximum changes of only 17%. Compared with 4 mo of bed rest without an exercise countermeasure, the losses in the soleus and gastrocnemius during 4-6.5 mo of spaceflight are about half the expected level, suggesting a substantial positive effect from the exercise countermeasure program. The losses in the thigh and back are similar to losses during bed rest, indicating less effectiveness in these regions. The data show considerable individual variability, which may be due, in part, to differences in crew compliance with the exercise regime because of personal preference or the exigencies of the mission (11). For example, exercise is generally not possible for the first 20 days of flight because of scheduling constraints early in the mission, whereas, in contrast, many crewmembers increase their exercise intensity in the weeks just before return to Earth. Reports from returning crew also indicate significant variability among crew in the amount, scheduling, and type of exercise performed during flight. Therefore, at present, it is difficult to assess quantitatively the effectiveness of the current countermeasure program if conducted with full compliance, but it does appear to attenuate changes in some muscles compared with bed rest of similar duration and further demonstrates the utility of exercise as a countermeasure to spaceflight muscle atrophy.

Muscle T2. The cephalic fluid shift that occurs during spaceflight has been described and is thought to result in a diuresis during the first few days in space. After return to gravity, this fluid is regained within the first 24 h after landing (12). The reduced fluid volume and loss in vascular compliance during microgravity and the subsequent pooling of blood in the lower limbs after return from space is believed to be the cause of the commonly observed orthostatic intolerance experienced by astronauts after flight (2). There are fluid shifts during 6° and horizontal bed rest which, importantly, revert essentially to baseline within 30 min of resumption of upright ambulation (3). There is also a fluid shift that results from changing from standing to a lying position, and, therefore, it is important to allow sufficient time before the MRI measurements for these transient shifts to normalize. For this purpose, our subjects are horizontal on the MRI table at least 30 min before the calf measurements are obtained. Repeated measurements on volunteers in our laboratory (A. LeBlanc, unpublished data) have shown that this amount of time is more than adequate, i.e., from 15 to 110 min after lying down from a standing position, the muscle volume changes are <1%. The calf muscle volume changes between landing day and 2-4 days after landing clearly indicate that fluid moves into the lower limb muscles after flight. Similar observations have been observed on reambulation after bed rest (15). In both the shorter duration Spacelab and shuttle/Mir missions, calf muscle T2 is elevated and remains elevated for several weeks, a time frame very similar to a pattern observed after muscle damage (6, 14). In several crewmembers, T2 at day 14 was higher than that at day 2-4, which would not be expected if gravity-related fluid shifts were the explanation for the volume changes. In any case, others have shown that passive fluid shifts do not alter muscle T2 (3). Also, we have shown that muscle T2 does not appear to change during bed rest but is elevated after reambulation (13). The apparent swelling, along with prolonged elevation of muscle T2, is indicative of muscle damage. These results support the findings obtained from animal studies that provide evidence of interstitial edema and muscle damage after weight bearing after hindlimb suspension and spaceflight (23-24). Interestingly, in both the short- and long-duration missions, the largest volume changes are seen in the gastrocnemius. This may reflect greater functional disuse of this muscle group during flight because the position with leg bent at the knee is commonly assumed by crewmembers during flight. These postflight muscle changes need further investigation. Finally, these results suggest that, to determine the effects of microgravity on muscle physiology, measurements must be performed in-flight or shortly after return to Earth's gravity, before significant reambulation occurs.

Body composition. Not surprisingly, loss in BMC is not uniform throughout the skeleton but varies with location. Previous reports have shown that the percent loss in the proximal hip and lumbar spine are similar, but two to three times greater than the total body loss (22). It is clear from the results presented here that most of the total loss is from the pelvis and legs. Expressing regional loss as a percentage of the total loss shows that 97% of the total bone loss originates from the pelvis and leg bones. If we assume that ~5% (same as lumbar spine) of the loss in BMC of the leg represents the proximal hip, >90% of the bone loss during spaceflight is not reflected in the hip and spine scans that are normally used to judge changes in bone mass or density.