The effect of weightlessness on the human skeletal system is one of the greatest concerns in safely extending space missions [1–11]. The ability to understand and counteract weightlessness-induced bone mineral loss will be vital to crew health and safety during and after extended-duration space sta- tion and exploration missions [1–7]. Research on bone mineral loss during space flight has gone on for more than half a century, and recent studies have shown significant progress in developing coun- termeasures that have proved to be effective, including good nutrition and exercise. We review the history of this research here and provide a summary of recent and ongoing studies, including efforts to counteract bone and calcium loss resulting from weightlessness. Unfortunately, the most obvious nutritional countermeasure—providing excess calcium—does not protect against bone loss . This result is likely related to the decreased calcium absorption observed in space flight and in ground-based models [13–16]. Phosphate supplementation was also ineffective at reducing calcium excretion . Combination therapy with calcium and phosphorus was also unsuccessful at mitigating bone loss and hypercalciuria . Other nutrients, specifically sodium, protein, potassium, vitamin K, and omega-3 fatty acids, have also been proposed and/or tested as bone loss countermeasures , and are discussed in more detail below.
Research Containing: Countermeasure
Bone loss associated with microgravity exposure poses a significant barrier to long-duration spaceflight. Osteoprotegerin-Fc (OPG-Fc) is a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor that causes sustained inhibition of bone resorption after a single subcutaneous injection. We tested the ability of OPG-Fc to preserve bone mass during 12 days of spaceflight (SF). 64-day-old female C57BL/6J mice (n=12/group) were injected subcutaneously with OPG-Fc (20mg/kg) or an inert vehicle (VEH), 24h prior to launch. Ground control (GC) mice (VEH or OPG-Fc) were maintained under environmental conditions that mimicked those in the space shuttle middeck. Age-matched baseline (BL) controls were sacrificed at launch. GC/VEH, but not SF/VEH mice, gained tibia BMD and trabecular volume fraction (BV/TV) during the mission (P<0.05 vs. BL). SF/VEH mice had lower BV/TV vs. GC/VEH mice, while SF/OPG-Fc mice had greater BV/TV than SF/VEH or GC/VEH. SF reduced femur elastic and maximum strength in VEH mice, with OPG-Fc increasing elastic strength in SF mice. Serum TRAP5b was elevated in SF/VEH mice vs. GC/VEH mice. Conversely, SF/OPG-Fc mice had lower TRAP5b levels, suggesting that OPG-Fc preserved bone during spaceflight via inhibition of osteoclast-mediated bone resorption. Decreased bone formation also contributed to the observed osteopenia, based on the reduced femur periosteal bone formation rate and serum osteocalcin level. Overall, these observations suggest that the beneficial effects of OPG-Fc during SF are primarily due to dramatic and sustained suppression of bone resorption. In growing mice, this effect appears to compensate for the SF-related inhibition of bone formation, while preventing any SF-related increase in bone resorption. We have demonstrated that the young mouse is an appropriate new model for SF-induced osteopenia, and that a single pre-flight treatment with OPG-Fc can effectively prevent the deleterious effects of SF on mouse bone.
The medical care for the integrated crew of the International Space Station (ISS) will require close co-operation between the partner agencies in the areas of selection, medical surveillance, countermeasures, and handling of acute medical problems. Based on a commonly accepted policy of shared care and responsibilities medical guidelines, procedures, and standards for medical data and communication need to be harmonised under the responsibility of the Multilateral Medical Operations Panel (MMOP). A supporting telemedical network connecting the partners on an organisational and technical level will facilitate the harmonisation process and provide new tools for effective co-operation between medical professionals. Earth bound projects with similar application areas can profit from and contribute to this development and need to be considered for efficient implementation and exploitation.
PURPOSE: Exposure to microgravity affects human physiology and results in changes in urinary chemical composition during and after spaceflight, favoring an increased risk of renal stones. We assessed the efficacy of potassium citrate to decrease the stone risk during and after spaceflight. MATERIALS AND METHODS: The study was done in 30 long duration spaceflight crew members to the space stations Mir and International Space Station. Before, during and after spaceflight 24-hour urine samples were collected to assess the renal stone risk. Potassium citrate (20 mEq) was ingested daily by International Space Station crew members in a double-blind, placebo controlled study. Mir crew members performed the identical protocol but did not ingest medication. RESULTS: Potassium citrate treated crew members had decreased urinary calcium excretion and maintained the calcium oxalate supersaturation risk at preflight levels compared to that in controls. Increased urinary pH in the treatment group decreased the risk of uric acid stones. CONCLUSIONS: Results from this investigation suggest that supplementation with potassium citrate may decrease the risk of renal stone formation during and immediately after spaceflight.
The aim of this investigation was to document the exercise program used by crewmembers (n = 9; 45 ± 2 yr) while aboard the International Space Station (ISS) for 6 mo and examine its effectiveness for preserving calf muscle characteristics. Before and after spaceflight, we assessed calf muscle volume (MRI), static and dynamic calf muscle performance, and muscle fiber types (gastrocnemius and soleus). While on the ISS, crewmembers had access to a running treadmill, cycle ergometer, and resistance exercise device. The exercise regimen varied among the crewmembers with aerobic exercise performed ∼5 h/wk at a moderate intensity and resistance exercise performed 3–6 days/wk incorporating multiple lower leg exercises. Calf muscle volume decreased (P < 0.05) 13 ± 2% with greater (P < 0.05) atrophy of the soleus (−15 ± 2%) compared with the gastrocnemius (−10 ± 2%). Peak power was 32% lower (P < 0.05) after spaceflight. Force-velocity characteristics were reduced (P < 0.05) −20 to −29% across the velocity spectrum. There was a 12–17% shift in myosin heavy chain (MHC) phenotype of the gastrocnemius and soleus with a decrease (P < 0.05) in MHC I fibers and a redistribution among the faster phenotypes. These data show a reduction in calf muscle mass and performance along with a slow-to-fast fiber type transition in the gastrocnemius and soleus muscles, which are all qualities associated with unloading in humans. Future long-duration space missions should modify the current ISS exercise prescription and/or hardware to better preserve human skeletal muscle mass and function, thereby reducing the risk imposed to crewmembers.
Dynamics of physical performance during long-duration space flight (first results of "Countermeasure" experiment)
The efficacy of countermeasure exercise for diminishing disturbances induced by microgravity in motor system and its visceral supply during different stages of long-duration flight was evaluated. The results of both bicycle and locomotor testing indicate that physical fitness of cosmonaut does not become worse in the course of the long-duration flight. On the contrary, the lowest fitness was recorded at the first stage of mission, just after one month of flight. The "dead period" at the beginning of space flight seems to be a manifestation of the acute decrease in physical condition on transition from 1 G to microgravity, when none of the regular countermeasure regimes is sufficiently effective and acute increase of volume and intensity of training is impossible under the conditions of space flight.
The cardiovascular system undergoes major changes in stress with space flight primarily related to the elimination of the head-to-foot gravitational force. A major observation has been that the central venous pressure is not elevated early in space flight yet stroke volume is increased at least early in flight. Recent observations demonstrate that heart rate remains lower during the normal daily activities of space flight compared to Earth-based conditions. Structural and functional adaptations occur in the vascular system that could result in impaired response with demands of physical exertion and return to Earth. Cardiac muscle mass is reduced after flight and contractile function may be altered. Regular and specific countermeasures are essential to maintain cardiovascular health during long-duration space flight.
Right ventricular tissue Doppler assessment in space during circulating volume modification using the Braslet device
Introduction: This joint US–Russian work aims to establish a methodology for assessing cardiac function in microgravity in association with manipulation of central circulating volume. Russian Braslet-M (Braslet) occlusion cuffs were used to temporarily increase the volume of blood in the lower extremities, effectively reducing the volume in central circulation. The methodology was tested at the International Space Station (ISS) to assess the volume status of crewmembers by evaluating the responses to application and release of the cuffs, as well as to modified Valsalva and Mueller maneuvers. This case study examines the use of tissue Doppler (TD) of the right ventricular (RV) free wall. Results: Baseline TD of the RV free wall without Braslet showed early diastolic E′ (16 cm/s), late diastolic A′ (14 cm/s), and systolic S′ (12 cm/s) velocities comparable with those in normal subjects on Earth. Braslet application caused 50% decrease of E′ (8 cm/s), 45% increase of A′, and no change to S′. Approximately 8 beats after the Braslet release, TD showed E′ of 8 cm/s, A′ of 12 cm/s, and S′ of 13 cm/s. At this point after release, E′ did not recover to baseline values while l A′ and S′ did recover. The pre-systolic cross-sectional area of the internal jugular vein without Braslet was 1.07 cm2, and 1.13 cm2 10 min after the Braslet was applied. The respective cross-sectional areas of the femoral vein were 0.50 and 0.54 cm2. The RV myocardial performance Tei index was calculated by dividing the sum of the isovolumic contraction time and isovolumic relaxation time by the ejection time ((IVCT+IVRT)/ET); baseline and Braslet-on values for Tei index were 0.25 and 0.22, respectively. Braslet Tei indices are within normal ranges found in healthy terrestrial subjects and temporarily become greater than 0.4 during the dynamic Braslet release portion of the study. Conclusions: TD modality was successfully implemented in space flight for the first time. TD of RV revealed that the Braslet influenced cardiac preload and that fluid was sequestered in the lower extremity interstitial and vascular space after only 10 min of application. This report demonstrates that Braslet application has an effect on RV physiology in long-duration space flight based on TD, and that this effect is in part due to venous hemodynamics.
Sedentary behavior has deleterious effects on the cardiovascular system, including reduced endothelial functions. A 2-mo bed rest study in healthy women [women international space simulation for exploration (WISE) 2005 program] presented a unique opportunity to analyze the specific effects of prolonged inactivity without other vascular risk factors on the endothelium. We investigated endothelial properties before and after 56 days of bed rest in 8 subjects who performed no exercise (control group: No-EX) and in 8 subjects who regularly performed treadmill exercise in a lower body negative pressure chamber as well as resistance exercise (countermeasure group, EX). A functional evaluation of the microcirculation in the skin was assessed with laser Doppler. We studied endothelium-dependent and -independent vasodilation using iontophoresis of acetylcholine and sodium nitroprusside, respectively. We also measured circulating endothelial cells (CECs), an index of endothelial damage. In the No-EX group, endothelium-dependent vasodilation was significantly reduced (35.4 ± 4.8% vs. 24.1 ± 3.8%, P < 0.05) by bed rest with a significant increase in the number of CECs (3.6 ± 1.4 vs. 10.6 ± 2.7 ml−1, P < 0.05). In the EX group, endothelium-dependent vasodilation and number of CECs were preserved. Our study shows that in humans prolonged bed rest causes impairment of endothelium-dependent function at the microcirculatory level, along with an increase in circulating endothelial cells. Microcirculatory endothelial dysfunction might participate in cardiovascular deconditioning, as well as in several bed rest-induced pathologies. We therefore conclude that the endothelium should be a target for countermeasures during periods of prolonged deconditioning.
Prolonged weightlessness results in a weakening of the heart, a loss of skeletal muscle strength and volume, and decreased bone density. At this time, the only effective treatment for these problems is in-flight exercise. The basic unit of exercise is a single twitch contraction of one motor unit. If spinal cord excitability (SCE) is reduced during space flight, this would hinder motor unit recruitment. As a result, more effort would be required to produce the same level of exercise, or if the same apparent effort were maintained, the actual level of exercise would decrease. If present after landing, it would be more difficult to stand and walk.