Brandon R. Macias

Evaluation of Treadmill Exercise in a Lower Body Negative Pressure Chamber as a Countermeasure for Weightlessness‐Induced Bone Loss: A Bed Rest Study With Identical Twins

Counteracting bone loss is required for future space exploration. We evaluated the ability of treadmill exercise in a LBNP chamber to counteract bone loss in a 30‐day bed rest study. Eight pairs of identical twins were randomly assigned to sedentary control or exercise groups. Exercise within LBNP decreased the bone resorption caused by bed rest and may provide a countermeasure for spaceflight.

WISE-2005: Supine treadmill exercise within lower body negative pressure and flywheel resistive exercise as a countermeasure to bed rest-induced bone loss in women during 60-day simulated microgravity☆

Bone loss associated with disuse during bed rest (BR), an analog of space flight, can be attenuated by exercise. In previous studies, the efficacy of either aerobic or resistive exercise countermeasures has been examined separately. We hypothesized that a regimen of combined resistive and aerobic exercise during BR would prevent bone resorption and promote bone formation. After a 20-day ambulatory adaptation to controlled confinement and diet, 16 women participated in a 60-day, 6 degrees head-down-tilt BR and were assigned randomly to one of the two groups. Control subjects (CON, n=8) performed no countermeasure. Exercise subjects (EX, n=8) participated in an exercise program during BR, alternating between supine treadmill exercise within lower body negative pressure (3-4 d wk(-1)) and flywheel resistive exercise (2-3 d wk(-1)). By the last week of BR, excretion of helical peptide (CON, 79%+/-44 increase; EX, 64%+/-50, mean+/-SD) and N-terminal cross-linking telopeptide (CON, 51%+/-34; EX, 43%+/-56), markers of bone resorption, were greater than they were before BR in both groups (P<0.05). However, serum concentrations of the bone formation marker procollagen type I N propeptide were greater in EX than CON throughout and after bed rest (P<0.05), while concentrations of the bone formation marker bone alkaline phosphatase tended to be greater in EX than CON. Dual-energy X-ray absorptiometry results indicated that the exercise treatment significantly (P<0.05) attenuated loss of hip and leg bone mineral density in EX compared to CON. The combination of resistive and aerobic exercise did not prevent bone resorption but did promote bone formation, and helped mitigate the net bone loss associated with simulated microgravity.

The Effect of Backpacks on the Lumbar Spine in Children: A Standing Magnetic Resonance Imaging Study

Study Design. This study is a repeated measures design to measure the lumbar spine response to typical school backpack loads in healthy children. The lumbar spine in this setting was measured for the first time by an upright magnetic resonance imaging (MRI) scanner. Objective. The purpose of this study is to measure the lumbar spine response to typical school backpack loads in healthy children. We hypothesize that backpack loads significantly increase disc compression and lumbar curvature. Summary of Background Data. Children commonly carry school backpacks of 10% to 22% bodyweight. Despite growing concern among parents about safety, there are no imaging studies which describe the effect of backpack loads on the spine in children. Methods. Three boys and 5 girls, age 11 ± 2 years (mean ± SD) underwent T2 weighted sagittal and coronal MRI scans of the lumbar spine while standing. Scans were repeated with 4, 8, and 12 kg backpack loads, which represented approximately 10%, 20%, and 30% body weight for our sample. Main outcome measures were disc compression, defined as post- minus preloading disc height, and lumbar asymmetry, defined as the coronal Cobb angle between the superior endplates of S1 and L1. Results. Increasing backpack loads significantly compressed lumbar disc heights measured in the midline sagittal plane (P < 0.05, repeated-measures analysis of variance [ANOVA]). Lumbar asymmetry was: 2.23° ± 1.07° standing, 5.46° ± 2.50° with 4 kg, 9.18° ± 2.25° with 8 kg, and 5.68° ± 1.76° with 12 kg (mean ± SE). Backpack loads significantly increased lumbar asymmetry (P < 0.03, one-way ANOVA). Four of the 8 subjects had Cobb angles greater than 10° during 8-kg backpack loads. Using a visual-analogue scale to rate their pain (0-no pain, 10-worst pain imaginable), subjects reported significant increases in back pain associated with backpack loads of 4, 8, and 12 kg (P < 0.001, 1-way ANOVA). Conclusion. Backpack loads are responsible for a significant amount of back pain in children, which in part, may be due to changes in lumbar disc height or curvature. This is the first upright MRI study to document reduced disc height and greater lumbar asymmetry for common backpack loads in children.

Asymmetric Loads and Pain Associated With Backpack Carrying by Children

Background: Shoulder and back pain in school children is associated with wearing heavy backpacks. Such pain may be attributed to the magnitude of the backpack load and the manner by which children distribute the load over their shoulders and back. The purpose of this study is to quantify the pressures under backpack straps of children while they carried a typical range of loads during varying conditions. Methods: Ten healthy children (aged, 12-14 years) wore a backpack loaded at 10%, 20%, and 30% body weight (BW). Backpacks were carried under 2 conditions, low on back or high on back. Pressure sensors (0.1 mm thick) measured pressures beneath the shoulder straps. Results: When walking with the backpack straps over both shoulders, contact pressures were significantly greater in the low-back condition than in the high-back condition (P = 0.004). In addition, when children carried the backpack in the low-back condition, mean pressures (±SE) over the right shoulder were as follows: 98 ± 31, 153 ± 48, and 170 ± 54 mm Hg at 10%, 20%, and 30% BW, respectively, which were significantly higher (P < 0.001) than those over the left shoulder (46 ± 14, 92 ± 29, and 90 ± 29 mm Hg, respectively). Perceived pain with the backpack over 1 shoulder was significantly greater (P = 0.002) than that for donning with both shoulders in the low-back condition. Conclusions: Pressures at 10%, 20%, and 30% BW loads on the right or left shoulder, during low-back or high-back conditions, are higher than the pressure thresholds (approximately 30 mm Hg) to occlude skin blood flow. Furthermore, asymmetric and high pressures exerted for extended periods of time may help explain the shoulder and back pain attributed to backpacks. Clinical Relevance: Randomized controlled trial. Grade 1 level of evidence.

Wise-2005: Exercise and Nutrition Countermeasures for Upright V˙o2pk during Bed Rest

PURPOSE Exercise prescriptions for spaceflight include aerobic and resistive countermeasures, yet few studies have evaluated their combined effects on exercise responses after real or simulated microgravity. We hypothesized that upright aerobic capacity (VO2pk) is protected during a 60-d bed rest (BR) in which intermittent (40%-80% pre-BR VO2pk) aerobic exercise (supine treadmill exercise against lower body negative pressure) was performed 2-4 d x wk(-1) and resistive exercise (inertial flywheel exercises) was performed 2-3 d x wk(-1). Further, we hypothesized that ingestion of an amino acid supplement that was shown previously to counteract muscle atrophy, would reduce the decline in VO2pk in nonexercising subjects during BR. METHODS Twenty-four healthy women (8 nonexercise controls (CON), 8 exercisers (EX), and 8 nonexercisers with nutritional supplementation (NUT)) underwent a 20-d ambulatory baseline period, 60 d of 6 degrees head-down tilt BR, and 21 d of ambulatory recovery. VO2pk was measured pre-BR and on the third day of recovery from BR (R3). RESULTS In the EX group, VO2pk (mean +/- SE) was not different from pre-BR (-3.3 +/- 1.2%) on R3, although it decreased significantly in the CON (-21.2 +/- 2.1%) and NUT (-25.6 +/- 1.6%) groups. CONCLUSIONS These results indicate that alternating aerobic and resistive exercise on most days during prolonged microgravity simulated by BR is sufficient to preserve or allow quick recovery of upright aerobic capacity in women but that a nutritional supplementation alone is not effective.

LBNP exercise protects aerobic capacity and sprint speed of female twins during 30 days of bed rest

We have shown previously that treadmill exercise within lower body negative pressure (LBNPex) maintains upright exercise capacity (peak oxygen consumption, Vo(2peak)) in men after 5, 15, and 30 days of bed rest (BR). We hypothesized that LBNPex protects treadmill Vo(2peak) and sprint speed in women during a 30-day BR. Seven sets of female monozygous twins volunteered to participate. Within each twin set, one was randomly assigned to a control group (Con) and performed no countermeasures, and the other was assigned to an exercise group (Ex) and performed a 40-min interval (40-80% pre-BR Vo(2peak)) LBNPex (51 +/- 5 mmHg) protocol, plus 5 min of static LBNP, 6 days per week. Before and immediately after BR, subjects completed a 30.5-m sprint test and an upright graded treadmill test to volitional fatigue. These results in women were compared with previously reported reductions in Vo(2peak) and sprint speed in male twins after BR. In women, sprint speed (-8 +/- 2%) and Vo(2peak) (-6 +/- 2%) were not different after BR in the Ex group. In contrast, both sprint speed (-24 +/- 5%) and Vo(2peak) (-16 +/- 3%) were significantly less after BR in the Con group. The effect of BR on sprint speed and Vo(2peak) after BR was not different between women and men. We conclude that treadmill exercise within LBNP protects against BR-induced reductions in Vo(2peak) and sprint speed in women and should prove effective during long-duration spaceflight.

Genetic Heritability of Urinary Stone Risk in Identical Twins

PURPOSE Quantitative measurements of urinary parameters are valuable clinical tools for predicting the risk of nephrolithiasis. To our knowledge no previous studies have evaluated the heritability of urinary stone risk in identical twins. Because these individuals share identical genetics, the R defined by their phenotypic data are theoretically equal to the entire population H2. MATERIALS AND METHODS A total of 12 sets of healthy homozygous twins, including 4 males and 8 females for a total of 24 individuals, with a mean age of 25.9 years (range 21 to 36) volunteered for this study. All subjects provided informed written consent before assessment. Urinary stone risk profiles were done elsewhere on 2 consecutive days after 5 days of a standardized diet (170 mEq Na and 2500 kcal). Linear regression was performed on the data to determine R. Because identical twins were used, R was theoretically an estimate of H2. RESULTS Certain urinary stone risk markers were highly heritable, including urinary calcium (94%), oxalate (94%), citrate (95%), uric acid (96%) and brushite supersaturation (90%), as determined by genotype (H2 90% or greater). Uric acid supersaturation (58%) and urinary sodium (64%) had low degrees of heritability. CONCLUSIONS H2 is a measure of how much of the total variance in phenotype results from differences in genotype, as opposed to environmental differences. For example, an H2 of 95% for citrate suggests that genetic differences account for 95% of the variation in urinary citrate and environmental differences account for the remaining 5%. Therefore urinary calcium, oxalate and citrate are primarily determined by genotype, while environmental factors, particularly those that impact urine pH and urinary volume, may be increasingly important for determining uric acid supersaturation.

Renal Stone Risk in a Simulated Microgravity Environment: Impact of Treadmill Exercise With Lower Body Negative Pressure

PURPOSE Prolonged exposure to microgravity during spaceflight causes metabolic changes that increase the risk of renal stone formation. Studies during the Gemini, Apollo, Skylab and Shuttle missions demonstrated alterations in renal function, fluid homeostasis and bone resorption that result in increased urinary supersaturation of calcium oxalate, brushite, sodium urate and uric acid. Developing countermeasures to increased urinary supersaturation is an important priority as the duration of space missions increases. MATERIALS AND METHODS A total of 11 sets of identical twins remained on 6-degree head down, tilt bed rest for 30 days to simulate prolonged microgravity. One twin per pair was randomly selected to exercise while supine in a lower body negative pressure chamber 6 days weekly for 40 minutes, followed by 5 minutes of resting lower body negative pressure at 50 mm Hg. The other twin served as a nonexercise control. Pressure in the exercise lower body negative pressure chamber (52 to 63 mm Hg) was adjusted to produce footward forces equivalent to those for upright running on Earth at 1.0 to 1.2 x body weight. Pre-bed rest urinary stone risk profiles were done elsewhere after 5 days of a standardized diet, consisting of 170 mEq sodium, 1,000 mg calcium, 0.8 gm/kg animal protein and 2,500 kcal, and then throughout the bed rest and recovery phases of the protocol. RESULTS A significant increase in urinary calcium after just 1 week of bed rest was noted in the nonexercise control group (p = 0.001). However, no such increase was noted in the exercise group. Brushite supersaturation increased significantly from bed rest in each group, although the increase was significantly higher in the nonexercise control group than in the exercise group (p = 0.006). Calcium oxalate supersaturation increased during bed rest in the exercise group (p = 0.004). It trended toward a higher level in the nonexercise control group, although this did not achieve significance (p = 0.055) Mean urine volume +/- SD was significantly higher in the nonexercise control group than in the exercise group at bed rest week 2 and at week 3 (2.01 +/- 0.21 vs 1.63 0.18 l and 2.03 +/- 0.22 vs 1.81 +/- 0.20, respectively). Urinary pH was significantly higher in the nonexercise control group than in the exercise group at week 1 and week 3 (6.62 +/- 0.7 vs 6.49 +/- 0.5 and 6.58 +/- 0.6 vs 6.49 +/- 0.8, respectively, p = 0.01). CONCLUSIONS Bed rest significantly alters the urinary environment to favor calculous formation. Lower body negative pressure chamber treadmill exercise offers some protection against increases in stone risk during simulated microgravity, particularly with regard to the risks of hypercalciuria and brushite stone formation. The use of lower body negative pressure to augment aerobic exercise in space may decrease the risk of stone formation in astronauts. Adjunct measures, including aggressive hydration and alkalinization therapy, should be considered.

Intraocular and intracranial pressures during head-down tilt with lower body negative pressure.

BACKGROUND Seven astronauts after 6-mo missions to the International Space Station showed unexpected vision problems. Lumbar punctures performed in the four astronauts with optic disc edema showed moderate elevations of cerebral spinal fluid pressure after returning to Earth. We hypothesized that lower body negative pressure (LBNP) imposed during head-down tilt (HDT) would reduce intraocular pressure (IOP) and transcranial ultrasound pulse amplitude, a noninvasive intracranial pressure (ICP) surrogate. METHODS Participating in this study were 25 normal healthy nonsmoking volunteers (mean age: 36 yr). Subjects were positioned supine (5 min), sitting (5 min), 15° whole body HDT (5 min), and 10 min of HDT with LBNP (25 mmHg). The order of HDT and HDT+LBNP tests was balanced. Right and left IOP, transcranial ultrasound pulse amplitude, arm blood pressure, and heart rate were measured during the last minute (steady state) of each testing condition. RESULTS IOP significantly decreased from supine to sitting posture by 3.2 ± 1.4 mmHg (mean ± SD: N = 25), and increased by 0.9 ± 1.3 mmHg from supine to the HDT position. LBNP during HDT significantly lowered IOP to supine levels. In addition, LBNP significantly reduced transcranial ultrasound pulse amplitudes by 38% as compared to the HDT condition (N = 9). Sitting mean blood pressure (BP) was significantly higher (+5 mmHg) than BP values after 10 min of LBNP during HDT. However, heart rate was not significantly different across all conditions. DISCUSSION These data suggest that short duration exposures to LBNP attenuate HDT-induced increases in IOP and ICP. Macias BR, Liu JHK, Grande-Gutierrez N, Hargens AR. Intraocular and intracranial pressures during head-down tilt with lower body negative pressure.

Simulated resistance training, but not alendronate, increases cortical bone formation and suppresses sclerostin during disuse.

Mechanical loading modulates the osteocyte-derived protein sclerostin, a potent inhibitor of bone formation. We hypothesized that simulated resistance training (SRT), combined with alendronate (ALEN) treatment, during hindlimb unloading (HU) would most effectively mitigate disuse-induced decrements in cortical bone geometry and formation rate (BFR). Sixty male, Sprague-Dawley rats (6-mo-old) were randomly assigned to either cage control (CC), HU, HU plus either ALEN (HU+ALEN), or SRT (HU+SRT), or combined ALEN and SRT (HU+SRT/ALEN) for 28 days. Computed tomography scans on days -1 and 28 were taken at the middiaphyseal tibia. HU+SRT and HU+SRT/ALEN rats were subjected to muscle contractions once every 3 days during HU (4 sets of 5 repetitions; 1,000 ms isometric + 1,000 ms eccentric). The HU+ALEN and HU+SRT/ALEN rats received 10 μg/kg ALEN 3 times/wk. Compared with the CC animals, HU suppressed the normal slow growth-induced increases of cortical bone mineral content, cortical bone area, and polar cross-sectional moment of inertia; however, SRT during HU restored cortical bone growth. HU suppressed middiaphyseal tibia periosteal BFR by 56% vs. CC (P < 0.05). However, SRT during HU restored BFR at both periosteal (to 2.6-fold higher than CC) and endocortical (14-fold higher than CC) surfaces (P < 0.01). ALEN attenuated the SRT-induced BFR gains during HU. The proportion of sclerostin-positive osteocytes in cortical bone was significantly higher (+121% vs. CC) in the HU group; SRT during HU effectively suppressed the higher proportion of sclerostin-positive osteocytes. In conclusion, a minimum number of high-intensity muscle contractions, performed during disuse, restores cortical BFR and suppress unloading-induced increases in sclerostin-positive osteocytes.