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Interactions between muscle and the immune system during modified musculoskeletal loading

Interactions between the immune system and skeletal muscle may play a significant role in modulating the course of muscle injury and repair after modified musculoskeletal loading. Current evidence indicates that activation of the complement system is an early event during modified loading, which then leads to inflammatory cell invasion. However, the functions of those inflammatory cells are complex and they seem to be capable of promoting additional injury and repair. Recent findings implicate an early invading neutrophil population in increasing muscle damage that is detected by the presence of muscle membrane lesions. Macrophages that invade subsequently serve to remove cellular debris, and seem to promote repair. However, macrophages also have the ability to increase damage in muscle in which there is an impaired capacity to generate nitric oxide. In vivo and in vitro evidence indicates that muscle-derived nitric oxide can serve an important role in protecting muscle from membrane damage by invading inflammatory cells. Collectively, these findings indicate that the dynamic balance between inflammatory cells, the complement system, and muscle-derived free radicals can play important roles in the secondary damage of muscle during modified musculoskeletal loading.

Review↗

The use of biomechanics in the study of movement in microgravity

As biomechanists interested in the adaptability of the human body to microgravity conditions, it appears that our job is not only to make sure that the astronauts can function adequately in space but also that they can function upon their return to Earth. This is especially significant since many of the projects now being designed at NASA concern themselves with humans performing for up to 3 years in microgravity. While the Extended Duration Orbiter flights may last 30 to 60 days, future flights to Mars using current propulsion technology may last from 2 to 3 years. It is for this range of time that the adaptation process must be studied. Specifically, biomechanists interested in space travel realize that human performance capabilities will change as a result of exposure to microgravity. The role of the biomechanist then is to first understand the nature of the changes realized by the body. These changes include adaptation by the musculoskeletal system, the nervous system, cardiorespiratory system, and the cardiovascular system. As biomechanists, it is also our role to take part in the development of countermeasure programs that involve some form of regular exercise. Exercise countermeasure programs should include a variety of modalities with full knowledge of the loads imposed on the body by these modalities. Any exercise programs that are to be conducted by the astronauts during space travel must consider the fact that the musculoskeletal and neuromuscular systems degrade as a function of flight duration. Additionally, it must be understood that the central nervous system modifies its output in the control of the human body during space flight and most importantly, we must prepare the astronauts for their return to one g.

Gregor, R. J.↗

USSR space life sciences digest, issue 27

This is the twenty-fifth issue of NASA's Space Life Sciences Digest. It contains abstracts of 30 journal papers or book chapters published in Russian and of 2 Soviet monographs. Selected abstracts are illustrated with figures and tables from the original. The abstracts in this issue have been identified as relevant to 18 areas of space biology and medicine. These areas include: adaptation, aviation medicine, biological rhythms, biospherics, botany, cardiovascular and respiratory systems, endocrinology, enzymology, exobiology, habitability and environmental effects, hematology, immunology, metabolism, musculoskeletal system, neurophysiology, radiobiology, and space medicine. A Soviet book review of a British handbook of aviation medicine and a description of the work of the division on aviation and space medicine of the Moscow Physiological Society are also included.

Stone, Lydia Razran↗

Computational Analysis of Artificial Gravity as a Possible Countermeasure to Spaceflight Induced Bone Loss

During exploration class missions, such as to asteroids and Mars, astronauts will be exposed to reduced gravity for extended periods. Data has shown that astronauts lose bone mass at a rate of 1% to 2% a month in microgravity, particularly in lower extremities such as the proximal femur. Exercise countermeasures have not completely eliminated bone loss from long duration spaceflight missions, which leaves astronauts susceptible to early onset osteoporosis and greater risk of fracture. Introduction of the Advanced Resistive Exercise Device and other large exercise devices on the International Space Station (ISS), coupled with improved nutrition, has further minimized bone loss. However, unlike the ISS, exploration vehicles will have very limited volume and power available to accommodate such capabilities. Therefore, novel concepts like artificial gravity systems are being explored as a means to provide sufficient load stimulus to the musculoskeletal system to mitigate bone changes that may lead to early onset osteoporosis and increased risk of fracture. Currently, there is minimal data available to drive further research and development efforts to appropriately explore such options. Computational modeling can be leveraged to gain insight on the level of osteoprotection that may be achieved using artificial gravity produced by a spinning spacecraft or centrifuge. With this in mind, NASA's Digital Astronaut Project (DAP) has developed a bone remodeling model that has been validated for predicting volumetric bone mineral density (vBMD) changes of trabecular and cortical bone both for gravitational unloading condition and the equivalent of 1g daily load stimulus. Using this model, it is possible to simulate vBMD changes in trabecular and cortical bone under different gravity conditions. In this presentation, we will discuss our preliminary findings regarding if and how artificial gravity may be used to mitigate spaceflight induced bone loss.

Mulugeta, L.↗

USSR Space Life Sciences Digest, issue 32

This is the thirty-second issue of NASA's USSR Space Life Sciences Digest. It contains abstracts of 34 journal or conference papers published in Russian and of 4 Soviet monographs. Selected abstracts are illustrated with figures and tables from the original. The abstracts in this issue have been identified as relevant to 18 areas of space biology and medicine. These areas include: adaptation, aviation medicine, biological rhythms, biospherics, cardiovascular and respiratory systems, developmental biology, exobiology, habitability and environmental effects, human performance, hematology, mathematical models, metabolism, microbiology, musculoskeletal system, neurophysiology, operational medicine, and reproductive system.

Stone, Lydia Razran↗

Immune responses in space flight

Space flight has been shown to have profound effects on immunological parameters of humans, monkeys and rodents. These studies have been carried out by a number of different laboratories. Among the parameters affected are leukocyte blastogenesis, natural killer cell activity, leukocyte subset distribution, cytokine production - including interferons and interleukins, and macrophage maturation and activity. These changes start to occur only after a few days space flight, and some changes continue throughout long-term space flight. Antibody responses have received only very limited study, and total antibody levels have been shown to be increased after long-term space flight. Several factors could be involved in inducing these changes. These factors could include microgravity, lack of load-bearing, stress, acceleration forces, and radiation. The mechanism(s) for space flight-induced changes in immune responses remain(s) to be established. Certainly, there can be direct effects of microgravity, or other factors, on cells that play a fundamental role in immune responses. However, it is now clear that there are interactions between the immune system and other physiological systems that could play a major role. For example, changes occurring in calcium use in the musculoskeletal system induced by microgravity or lack of use could have great impact on the immune system. Most of the changes in immune responses have been observed using samples taken immediately after return from space flight. However, there have been two recent studies that have used in-flight testing. Delayed-type hypersensitivity responses to common recall antigens of astronauts and cosmonauts have been shown to be decreased when tested during space flights. Additionally, natural killer cell and blastogenic activities are inhibited in samples taken from rats during space flight. Therefore, it is now clear that events occurring during space flight itself can affect immune responses. The biological significance of space flight-induced changes in immune parameters remains to be established; however, as duration of flights increases, the potential for difficulties due to impaired immune responses also increases.

manned↗

Humans in Earth Orbit and Planetary Exploration Missions; IAA Man in Space Symposium, 8th, Tashkent, Uzbek SSR, Sept. 29-Oct. 3, 1990, Selection of Papers

The present conference on findings from space life science investigations relevant to long-term earth orbit and planetary exploration missions, as well as considerations for future research projects on these issues, discusses the cardiovascular system and countermeasures against its deterioration in the microgravity environment, cerebral and sensorimotor functions, findings to date in endocrinology and immunology, the musculoskeletal system, and health maintenance and medical care. Also discussed are radiation hazards and protective systems, life-support and habitability factors, and such methodologies and equipment for long space mission research as the use of animal models, novel noninvasive techniques for space crew health monitoring, and an integrated international aerospace medical information system.

Grigor'ev, A. I.↗

USSR Space Life Sciences Digest, issue 4

The fourth issue of NASA's USSR Space Life Science Digest includes abstracts for 42 Soviet periodical articles in 20 areas of aerospace medicine and space biology and published in Russian during the last third of 1985. Selected articles are illustrated with figures and tables from the original. In addition, translated introductions and tables of contents for 17 Russian books on 12 topics related to NASA's life science concerns are presented. Areas covered are: adaptation, biological rhythms, biospherics, body fluids, botany, cardiovascular and respiratory systems, cytology, developmental biology, endocrinology, exobiology, habitability and environmental effects, health and medical treatment, hematology, histology, human performance, immunology, mathematical modeling, metabolism, microbiology, musculoskeletal system, neurophysiology, nutrition, perception, personnel selection, psychology, and radiobiology. Two book reviews translated from the Russian are included and lists of additional relevant titles available in English with pertinent ordering information are given.

Hooke, L. R.↗

Overview of LBNP Exercise as a Countermeasure for Long-Duration Space Flight

Theoretically, an integrated countermeasure for extended exposure to microgravity should combine high loads on the musculoskeletal system, normal regional distributions of transmural pressure across blood vessels and stimulation of normal neuromuscular locomotor patterns. Our strategy was to develop an exercise apparatus which induces cardiovascular and musculoskeletal strains equal to or greater than those on Earth without the need for a costly centrifugation apparatus. An LBNP chamber was designed to contain a treadmill upon which 8 male bed-rest subjects could exercise daily in supine posture for 40 min at cardiovascular and musculoskeletal loads up to 120% of those in upright posture on Earth. We undertook two 14 day bed-rest studies to investigate the mechanism of action and efficacy of our LBNP exercise concept. We examined the same 8 subjects in both 14 day bed rest (6 deg. head-down tilt, HDT) studies, assigning 4 subjects to 40 minutes of supine running exercise per day up to 1.2 BW of footward force, while the remaining 4 subjects constituted the non-exercise "control" group. Three months after the first 14 day HDT study, the two groups were reversed so that the previous non-exercise group received the same 40 min of supine jogging per day up to 1.2 BW, while the previously-exercised group did not exercise during the 14 days of HDT. This panel reviews the results obtained from an integrated, multiple system standpoint.

Hargens, Alan R.↗

Recent bed rest results and countermeasure development at NASA

Bedrest studies of normal subjects provide opportunities to understand physiologic responses to supine posture and inactivity. Furthermore, head-down tilt has been a valuable procedure to investigate adaptation to microgravity and development of countermeasures to maintain the health and well-being of humans during space-flight. Recent bedrest experiments at NASA have ranged in duration from a few hours to 17 weeks. Acute studies of 6 degrees head-down tilt indicate that elevation of capillary blood pressure from 28 to 34 mm Hg and increased capillary perfusion in tissues of the head cause facial and intracranial edema. Intracranial pressure increases from 2 to 17 mm Hg going from upright posture to 6 degrees head-down tilt. Microvessels of the head have a low capacity to constrict and diminish local perfusion. Elevation of blood and tissue fluid pressures/flow in the head may also explain the higher headward bone density associated with long-term head-down tilt. These mechanistic studies of head-down tilt, along with a better understanding of the relative stresses involved with upright posture and lower body negative pressure, have facilitated development of suitable physiologic countermeasures to maintain astronaut health during microgravity. Presently no exercise hardware is available to provide a blood pressure gradient from head to feet in space. However, recent studies in our laboratory suggest that treadmill exercise using a graded lower-body compression suit and 100 mmHg lower body negative pressure provides equivalent or greater physiologic stress than similar upright exercise on Earth. Therefore, exercise within a lower body negative pressure chamber may provide a cost-effective and simple countermeasure to maintain the cardiovascular and neuro-musculoskeletal systems of astronauts during long-duration flight.

manned↗

Lower limb kinematics during treadmill walking after space flight: implications for gaze stabilization

We examined the lower limb joint kinematics observed during pre- and postflight treadmill walking performed by seven subjects from three Space Shuttle flights flown between March 1992 and February 1994. Basic temporal characteristics of the gait patterns, such as stride time and duty cycle, showed no significant changes after flight. Evaluation of phaseplane variability across the gait cycle suggests that postflight treadmill walking is more variable than preflight, but the response throughout the course of a cycle is joint dependent and, furthermore, the changes are subject dependent. However, analysis of the phaseplane variability at the specific locomotor events of heel strike and toe off indicated statistically significant postflight increases in knee variability at the moment of heel strike and significantly higher postflight hip joint variability at the moment of toe off. Nevertheless, the observation of component-specific variability was not sufficient to cause a change in the overall lower limb joint system stability, since there was no significant change in an index used to evaluate this at both toe off and heel strike. The implications of the observed lower limb kinematics for head and gaze control during locomotion are discussed in light of a hypothesized change in the energy attenuation capacity of the musculoskeletal system in adapting to weightlessness.

NASA Discipline Number 16-10↗

Mineral and nitrogen balance study observations - The second manned Skylab mission

A metabolic study of important body elements, particularly those of the musculoskeletal system, was carried out on the astronauts of the Skylab 3 mission during the preflight, inflight, and postflight phases. An elevation in the level of urinary calcium similar to that observed in the 28-d Skylab flight continued throughout the flight. Significant nitrogen and phosphorus losses, apparently associated with muscle tissue loss, occurred in spite of inflight exercise programs. On the basis of these results it is predicted that capable musculoskeletal function is likely to occur in flights longer than about 9 months in duration.

Whedon, G. D.↗

Low Magnitude Mechanical Signals Reduce Risk-Factors for Fracture during 90-Day Bed Rest

Long duration spaceflight leads to multiple deleterious changes to the musculoskeletal system, where loss of bone density, an order of magnitude more severe than that which follows the menopause, combined with increased instability, conspire to elevate the risk of bone fracture due to falls on return to gravitational fields. Here, a ground-based analog for spaceflight is used to evaluate the efficacy of a low-magnitude mechanical intervention, VIBE (Vibrational Inhibition of Bone Erosion), as a potential countermeasure to preserve musculoskeletal integrity in the face of disuse. Twenty-six subjects consented to ninety days of six-degree head-down tilt bed-rest. 18 completed the 90d protocol, 8 of which received daily 10-minute exposure to 30 Hz, 0.3g VIBE, applied in the supine position using a vest elastically coupled to the vibrating platform. The shoulder harness induced a load of 60% of the subjects body weight. At baseline and 90d, Qualitative Ultrasound Scans (QUS) of the calcaneus and CT-scans of the hip and spine were performed to measure changes in bone density. Postural control (PC) was assessed through center of pressure (COP) recordings while subjects stood on a force platform for 4 minutes of quiet stance with eyes closed, and again with eyes opened. As compared to control bedrest subjects,

Muir, J. W.↗

Musculoskeletal adaptations to weightlessness and development of effective countermeasures

A Research Roundtable, organized by the American College of Sports Medicine with sponsorship from the National Aeronautics and Space Administration, met in November 1995 to define research strategies for effective exercise countermeasures to weightlessness. Exercise was considered both independently of, and in conjunction with, other therapeutic modalities (e.g., pharmacological nutritional, hormonal, and growth-related factors) that could prevent or minimize the structural and functional deficits involving skeletal muscle and bone in response to chronic exposure to weightlessness, as well as return to Earth baseline function if a degree of loss is inevitable. Musculoskeletal deficits and countermeasures are described with respect to: 1) muscle and connective tissue atrophy and localized bone loss, 2) reductions in motor performance, 3) potential proneness to injury of hard and soft tissues, and 4) probable interaction between muscle atrophy and cardiovascular alterations that contribute to the postural hypotension observed immediately upon return from space flight. In spite of a variety of countermeasure protocols utilized previously involving largely endurance types of exercise, there is presently no activity-specific countermeasure(s) that adequately prevent or reduce musculoskeletal deficiencies. It seems apparent that countermeasure exercises that have a greater resistance element, as compared to endurance activities, may prove beneficial to the musculoskeletal system. Many questions remain for scientific investigation to identify efficacious countermeasure protocols, which will be imperative with the emerging era of long-term space flight.

Non-NASA Center↗

Issues of exploration: human health and wellbeing during a mission to Mars

Today, the tools are in our hands to enable us to travel away from our home planet and become citizens of the solar system. Even now, we are seriously beginning to develop the robust infrastructure that will make the 21st century the Century of Space Travel. But this bold step must be taken with due concern for the health, safety and wellbeing of future space explorers. Our long experience with space biomedical research convinces us that, if we are to deal effectively with the medical and biomedical issues of exploration, then dramatic and bold steps are also necessary in this field. We can no longer treat the human body as if it were composed of muscles, bones, heart and brain acting independently. Instead, we must lead the effort to develop a fully integrated view of the body, with all parts connected and fully interacting in a realistic way. This paper will present the status of current (2000) plans by the National Space Biomedical Research Institute to initiate research in this area of integrative physiology and medicine. Specifically, three example projects are discussed as potential stepping stones towards the ultimate goal of producing a digital human. These projects relate to developing a functional model of the human musculoskeletal system and the heart. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

NASA Discipline General Space Life Sciences↗

Credibility Assessment and Evaluation of the Astronaut Musculoskeletal Boot/Ankle Injury Scenario Using Open SIM(TM) Computational Modeling

The musculoskeletal system of astronauts is subject to physiological changes, potentially leading to injuries due to the exposure to different gravitational environments experienced during spaceflight. These injuries can occur while an astronaut is performing an extravehicular activity (EVA) in space, on lunar or planetary surfaces or while wearing a spacesuit during terrestrial training for an EVA. One area of concern are injuries occurring at the feet and ankles due to a poor fit of the spacesuit boot. These injuries can occur if the boot does not support the ankle sufficiently and the astronaut steps awkwardly, twisting the ankle or foot, during an EVA. The OpenSimTM software can assess EVA induced musculoskeletal injuries for muscle strains, ligament injuries and joint injuries. A modeling and simulation credibility assessment of the OpenSim musculoskeletal modeling and simulation procedures, applied to the boot/ankle injury scenario injury mechanisms that may occur while carrying out tasks in these environments, is performed. These modeling and simulation credibility assessments give information on the credibility of the model’s use in simulating foot/ankle related injury mechanisms.

C A Gallo↗

Mineral and nitrogen balance study - Results of metabolic observations on Skylab II 28-day orbital mission

The prediction that various stresses of flight, particularly weightlessness, would bring about significant derangements in the metabolism of the musculoskeletal system has been based on various balance-study observations of long-term immobilized or inactive bed rest. The three astronauts of Skylab II consumed a planned dietary intake of major metabolic elements in mixed foods and beverages and provided virtually complete collections of excreta for 31 days preflight, 28 days inflight, and 17 days postflight. Analyses showed that, in varying degree among the crewmen, urinary calcium increased gradually during flight in a pattern similar to that observed in bed-rest studies. Fecal calcium excretion did not change significantly, but calcium balance, owing to the urinary calcium rise, became either negative or less positive than in preflight measurement. Increased excretion and negative nitrogen and phosphorus balances inflight indicated appreciable loss of muscle tissue in all three crewmen. Significant losses also occurred inflight in potassium, sodium, and magnesium. Based on the similarity in pattern and degree between these observations of calcium, phosphorus, and nitrogen loss, musculoskeletal integrity would not be threatened in space flights of up to at least 3 months. However, if similar changes occur in the planed Skylab flights for considerably more than 28 days, concern for capable musculoskeletal function should be serious for flights of very many months' duration.

Whedon, G. D.↗

Human skeletal muscle protein breakdown during spaceflight

Human spaceflight is associated with a loss of body protein. Excretion of 3-methylhistidine (3-MH) in the urine is a useful measurement of myofibrillar protein breakdown. Bed rest, particularly with 6 degrees head-down tilt, is an accepted ground-based model for human spaceflight. The objectives of this report were to compare 3-MH excretion from two Life Sciences shuttle missions (duration 9.5 and 15 days, n = 9) and from 17 days of bed rest (n = 7) with 6 degrees head-down tilt. The bed rest study was designed to mimic an actual Life Sciences spaceflight and so incorporated an extensive battery of physiological tests focused on the musculoskeletal system. Results showed that nitrogen retention, based on excretion of nitrogen in the urine, was reduced during both bed rest [from 22 +/- 1 to 1 +/- 5 mg N x kg(-1) x day(-1) (n = 7; P < 0.05)] and spaceflight [from 57 +/- 9 to 19 +/- 3 mg N x kg(-1) x day(-1) (n = 9; P < 0.05)]. 3-MH excretion was unchanged with either bed rest [pre-bed rest 5.30 +/- 0.29 vs. bed rest 5.71 +/- 0.30 micromol 3-MH x kg(-1) x day(-1), n = 7; P = not significant (NS)] or spaceflight [preflight 4.98 +/- 0.37 vs. 4.59 +/- 0.39 micromol 3-MH x kg(-1) x day(-1) in-flight, n = 9; P = NS]. We conclude that 1) 3-MH excretion was unaffected by spaceflight on the shuttle or with bed rest plus exercise, and 2) because protein breakdown (elevated 3-MH) was increased on Skylab but not on the shuttle, it follows that muscle protein breakdown is not an inevitable consequence of spaceflight.

STS-58 Shuttle Project↗