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NASA NTRS1989

Biomedical perspectives on locomotion in null gravity

A number of important features of various locomotor activities are discussed, and approaches to the study of these activities in the context of space flight are suggested. In particular, the magnitude of peak forces and the rates of change of force during terrestrial cycling, walking, and running are compared. It is shown that subtle changes in the conditions and techniques of locomotion can have a major influence on the biomechanical consequences to the skeleton. The various hypotheses that identify locomotor exercise as a countermeasure to bone demineralization during weightlessness deserve to be tested with some degree of biomechanical rigor. Various approaches for achieving such scrutiny are discussed.

Cavanagh, Peter R.↗

NASA NTRS1990

Spacelab Life Sciences 1 - Dedicated life sciences mission

The Spacelab Life Sciences 1 (SLS-1) mission is discussed, and an overview of the SLS-1 Spacelab configuration is shown. Twenty interdisciplinary experiments, planned for this mission, are intended to explore the early stages of human and animal physiological adaptation to space flight conditions. Biomedical and gravitational biology experiments include cardiovascular and cardiopulmonary deconditioning, altered vestibular functions, altered metabolic functions (including altered fluid-electrolyte regulation), muscle atrophy, bone demineralization, decreased red blood cell mass, and altered immunologic responses.

Womack, W. D.↗

NASA NTRS1992

Neurology of microgravity and space travel

Exposure to microgravity and space travel produce several neurologic changes, including SAS, ataxia, postural disturbances, perceptual illusions, neuromuscular weakness, and fatigue. Inflight SAS, perceptual illusions, and ocular changes are of more importance. After landing, however, ataxia, perceptual illusions, neuromuscular weakness, and fatigue play greater roles in astronaut health and readaptation to a terrestrial environment. Cardiovascular adjustments to microgravity, bone demineralization, and possible decompression sickness and excessive radiation exposure contribute further to medical problems of astronauts in space. A better understanding of the mechanisms by which microgravity adversely affects the nervous system and more effective treatments will provide healthier, happier, and longer stays in space on the space station Freedom and during the mission to Mars.

Fujii, M. D.↗

NASA NTRS1993

Endocrine and metabolic changes in payload specialist (L-1)

The endocrine system plays an important role in the adaptation to unusual environments by secreting hormones to control metabolism. Since human beings have long evolved on the surface of the Earth under a gravity environment, the weightless environment must be quite unusual for them. The purpose of this experiment is to study the mechanisms of human adaptation to a weightless environment from endocrine and metabolic changes. Our study plan is focused on four major physiological changes which were reported during past space flights or which may be expected to occur under that condition: (1) hormone and metabolic changes associated with fluid shift; (2) bone demineralization and muscle atrophy; (3) altered circadian rhythm; and (4) stress reaction during space flight.

Matsui, Nobuo↗

NASA NTRS1997

A Biomechanical Comparison of 1-G and Fully-Loaded Simulated Zero-Gravity Locomotion

Exercise will almost certainly play an integral part in minimizing the bone mineral loss and muscular atrophy that occur during spaceflight. It has been hypothesized that an effective exercise regimen can be developed to elicit loads on the lower extremities and require muscle actions which resemble those encountered on Earth. The Penn State Zero-Gravity Simulator (PSZS) is a device which suspends subjects horizontally from multiple latex cords, with each cord negating the weight of a limb segment. A treadmill mounted on the wall under the PSZS enables subjects to run in simulated 0G. Subjects wear a harness to which a number of springs, which provide a gravity replacement load, are connected. The opposite end of each spring is connected to the side of the treadmill. During exercise, astronauts currently wear a similar harness in which the spring tethering load pulls at both the waist and shoulders. Ground reaction forces, muscular activations, and joint angles of the left leg during overground, treadmill, and fully-loaded zero-gravity simulated (ZLS) locomotion were assessed in order to gain insight into the effectiveness of the exercise regimen used by NASA to prevent the muscular atrophy and bone demineralization which occur in weightlessness. There were three hypotheses to this research. It was hypothesized that there will be no differences in peak ground reaction forces and peak loading rates between overground gait and gait in the full body weight loaded conditions in the ZLS. A second hypothesis was that that there will be no differences in hip, knee, and ankle joint positions between walking or running overground, on a standard treadmill, and in full bodyweight loaded conditions in the ZLS. The third hypothesis was that the muscular activations, as a percentage of maximal voluntary contraction, will be similar between walking or running overground, on a standard treadmill, and in full body-weight loaded conditions in the ZLS.

McCrory, Jean L.↗

NASA NTRS1988

Vestibular factors influencing the biomedical support of humans in space

This paper will describe the biomedical support aspects of humans in space with respect to the vestibular system. The vestibular system is thought to be the primary sensory system involved in the short-term effects of space motion sickness although there is increasing evidence that many factors play a role in this complex set of symptoms. There is the possibility that an individual's inner sense of orientation may be strongly coupled with the susceptibility to space motion sickness. A variety of suggested countermeasures for space motion sickness will be described. Although there are no known ground-based tests that can predict space motion sickness, the search should go on. The long term effects of the vestibular system in weightlessness are still relatively unknown. Some preliminary data has shown that the otoconia are irregular in size and distribution following extended periods of weightlessness. The ramifications of this data are not yet known and because the data was obtained on lower order animals, definitive studies and results must wait until the space station era when higher primates can be studied for long durations. This leads us to artificial gravity, the last topic of this paper. The vestibular system is intimately tied to this question since it has been shown on Earth that exposure to a slow rotating room causes motion sickness for some period of time before adaptation occurs. If the artificial gravity is intermittent, will this mean that people will get sick every time they experience it? The data from many astronauts returning to Earth indicates that a variety of sensory illusions are present, especially immediately upon return to a 1-g environment. Oscillopsia or apparent motion of the visual surround upon head motion along with inappropriate eye motions for a given head motion, all indicate that there is much to be studied yet about the vestibular and CNS systems reaction to a sudden application of a steady state acceleration field like 1-g. From the above information it is obvious that the vestibular system does have unique requirements when it comes to the biomedical support of space flight. This is not to say that other areas such as cardiovascular, musculo-skeletal, immunological and hematological systems do not have their own unique requirements but that possible solutions to one system can provide continuing problems to another system. For example, artificial gravity might be helpful for long term stabilization of bone demineralization or cardiovascular deconditioning but might introduce a new set of problems in orientation, vestibular conflict and just plain body motion in a rotating space vehicle.

Non-NASA Center↗

NASA NTRS1999

Effects of microgravity on urinary osteopontin

Increased risk of renal stone formation during space flight has been linked primarily to increased calcium excretion from bone demineralization induced by space flight. Other factors contributing to increased risk include increased urinary calcium oxalate supersaturation, while urinary citrate, magnesium and volume are all decreased. The aim of this study was to increase the predictive value of stone risk profiles for crew members during space flight by evaluating the excretion of urinary protein inhibitors of calcium crystallization so that more comprehensive stone risk profiles could relate mineral saturation to the concentrations of inhibitor proteins. Levels of urinary osteopontin (uropontin) are reported in a series of 14 astronauts studied before, during, and after space flights. During space flight, a compensatory increase in uropontin excretion was not observed. However, the uropontin excretion of a majority of astronauts was increased during the period after space flight and was maximal at 2 wk after landing. The downward shift in the molecular size of uropontin observed in samples obtained during space flight was shown to result from storage at ambient temperature during flight, rather than an effect of microgravity on uropontin synthesis.

NASA Experiment Number 9401651↗

NASA NTRS2006

Space Life Sciences at NASA: Spaceflight Health Policy and Standards

In January 2005, the President proposed a new initiative, the Vision for Space Exploration. To accomplish the goals within the vision for space exploration, physicians and researchers at Johnson Space Center are establishing spaceflight health standards. These standards include fitness for duty criteria (FFD), permissible exposure limits (PELs), and permissible outcome limits (POLs). POLs delineate an acceptable maximum decrement or change in a physiological or behavioral parameter, as the result of exposure to the space environment. For example cardiovascular fitness for duty standards might be a measurable clinical parameter minimum that allows successful performance of all required duties. An example of a permissible exposure limit for radiation might be the quantifiable limit of exposure over a given length of time (e.g. life time radiation exposure). An example of a permissible outcome limit might be the length of microgravity exposure that would minimize bone loss. The purpose of spaceflight health standards is to promote operational and vehicle design requirements, aid in medical decision making during space missions, and guide the development of countermeasures. Standards will be based on scientific and clinical evidence including research findings, lessons learned from previous space missions, studies conducted in space analog environments, current standards of medical practices, risk management data, and expert recommendations. To focus the research community on the needs for exploration missions, NASA has developed the Bioastronautics Roadmap. The Bioastronautics Roadmap, NASA's approach to identification of risks to human space flight, revised baseline was released in February 2005. This document was reviewed by the Institute of Medicine in November 2004 and the final report was received in October 2005. The roadmap defines the most important research and operational needs that will be used to set policy, standards (define acceptable risk), and implement an overall Risk Management and Analysis process. Currently NASA is drafting spaceflight health standards for neurosensory alterations, space radiation exposure, behavioral health, muscle atrophy, cardiovascular fitness, immunological compromise, bone demineralization, and nutrition.

Davis, Jeffrey R.↗

NASA NTRS2010

Statistical Challenges in Biomedical Research

Potentially debilitating effects of spaceflight environment include: a) Bone Demineralization - Osteoporosis. b)Impaired Fracture Healing - Non-Union. c) Renal Stone Formation & Soft Tissue Calcification. d) Orthostatic Intolerance (on return to gravity). e) Cardiac Arrhythmias. f) Dehydration (on return to gravity). g) Decreased Aerobic Capacity. h) Impaired Coordination. i) Muscle Atrophy (Loss of Strength). j) Radiation Sickness. k) Increased Cancer Risk. l) Impaired Immune Function. m) Behavioral Changes & Performance Decrements n) Altitude Decompression Sickness during EVA.

Feiveson, Alan H.↗

NASA NTRS2003

Accomplishments in Bioastronautics Research Aboard International Space Station

The seventh long-duration expedition crew is currently in residence aboard International Space Station (ISS), continuing a permanent human presence in space that began in October 2000. During that time, expedition crews have been operators and subjects for 16 Human Life Sciences investigations, to gain a better understanding of the effects of long-duration space flight on the crew members and of the environment in which they live. Investigations have been conducted to study the radiation environment in the station as well as during extravehicular activity (EVA); bone demineralization and muscle deconditioning; changes in neuromuscular reflexes, muscle forces and postflight mobility; causes and possible treatment of postflight orthostatic intolerance; risk of developing kidney stones; changes in pulmonary function caused by long-duration flight as well as EVA; crew and crew-ground interactions; and changes in immune function. The experiment mix has included some conducted in flight aboard ISS as well as several which collected data only pre- and postflight. The conduct of these investigations has been facilitated by the Human Research Facility (HRF). HRF Rack 1 became the first research rack on ISS when it was installed in the US laboratory module Destiny in March 2001. The rack provides a core set of experiment hardware to support investigations, as well as power, data and commanding capability, and stowage. The second HRF rack, to complement the first with additional hardware and stowage capability, will be launched once Shuttle flights resume. Future years will see additional capability to conduct human research on ISS as International Partner modules and facility racks are added to ISS . Crew availability, both as a subject count and time, will remain a major challenge to maximizing the science return from the bioastronautics research program.

Uri, John J.↗

NASA NTRS2014

A Case for Hypogravity Studies Aboard ISS

Future human space exploration missions being contemplated by NASA and other spacefaring nations include some that would require long stays upon bodies having gravity levels much lower than that of Earth. While we have been able to quantify the physiological effects of sustained exposure to microgravity during various spaceflight programs over the past half-century, there has been no opportunity to study the physiological adaptations to gravity levels between zero-g and one-g. We know now that the microgravity environment of spaceflight drives adaptive responses of the bone, muscle, cardiovascular, and sensorimotor systems, causing bone demineralization, muscle atrophy, reduced aerobic capacity, motion sickness, and malcoordination. All of these outcomes can affect crew health and performance, particularly after return to a one-g environment. An important question for physicians, scientists, and mission designers planning human exploration missions to Mars (3/8 g), the Moon (1/6 g), or asteroids (likely negligible g) is: What protection can be expected from gravitational levels between zero-g and one-g? Will crewmembers deconditioned by six months of microgravity exposure on their way to Mars experience continued deconditioning on the Martian surface? Or, will the 3/8 g be sufficient to arrest or even reverse these adaptive changes? The implications for countermeasure deployment, habitat accommodations, and mission design warrant further investigation into the physiological responses to hypogravity. It is not possible to fully simulate hypogravity exposure on Earth for other than transient episodes (e.g., parabolic flight). However, it would be possible to do so in low Earth orbit (LEO) using the centrifugal forces produced in a live-aboard centrifuge. As we're not likely to launch a rotating human spacecraft into LEO anytime in the near future, we could take advantage of rodent subjects aboard the ISS if we had a centrifuge that could accommodate the rodent subjects for extended periods (weeks to months) at various hypogravity levels. Experiments aboard such a centrifuge could provide important insight into human exploration questions and simultaneously answer fundamental questions in gravitational physiology.

Paloski, William H.↗

NASA NTRS2013

Probabilistic Risk Assessment for Bone Fracture - Bone Fracture Risk Module (BFxRM)

This presentation summarizes the concepts, development, and application of NASA's Bone Fracture Risk Module (BFxRM). The overview includes an assessmnet of strenghts and limitations of the BFxRM and proposes a numebr of discussion questions to the panel regarding future development avenues for this simulation system.

Monte Carlo Method↗

NASA NTRS2018

The Turbolift: Linear Sled Hybrid Artificial Gravity Concept

Future crewed space exploration missions into deep space will require enhanced countermeasure technologies to ensure astronaut health. One such hazard is extended exposure to reduced gravity levels (i.e., microgravity, lunar gravity, or Martian gravity). Reduced gravity negatively impacts many physiological systems, leading to hydrostatic intolerance, musculoskeletal atrophy, sensorimotor impairment, bone demineralization, cardiovascular deconditioning, and visual alterations. Various countermeasures have been employed for mitigating these effects, such as exercise, pharmaceuticals, diet, and fluid loading. However, these approaches treat individual symptoms, such that each physiological system is addressed with typically one countermeasure. An alternative to this approach is artificial gravity (AG), which promises to be a holistic, comprehensive countermeasure. The traditional approach to creating AG is through centrifugation. However, centrifugation is not a "pure" form of AG and typically includes the drawbacks of Coriolis forces, gravity gradients, and vestibular cross-coupled illusions.As an alternative, we have proposed a Linear Sled Hybrid (LSH) AG system to mitigate astronauts' physiological deconditioning. This system functions by applying pure linear acceleration to produce footward loading. There is a half rotation (180_) to reorient the rider between acceleration and deceleration phases, such that the loading remains footward, as when standing on Earth. The rotation also provides some footward acceleration to the lower body through centripetal acceleration; hence the "hybrid" aspect of the design. At the end of the deceleration, the rider than accelerates back in the opposite direction and the sequence repeats.This proposed system could be integrated with future crewed space vehicles in a variety of manners.

Gruber, Jason↗

NASA NTRS1986

Selection of an appropriate animal model for study of bone loss in weightlessness

Prolonged weightlessness in space flight results in a slow progressive demineralization of bone accompanied by an increased calcium output in the urine resulting in negative calcium balances. This possibly irreversible bone loss may constitute a serious limiting factor to long duration manned space flight. A number of preventative measures have been suggested, i.e., exercise during flight, dietary calcium supplements, use of specific prophylactic drugs. In order to facilitate research in these areas it is necessary to develop appropriate ground-based animal models that simulate the human condition of osteoporsis. An appropriate animal model would permit bone density studies, calcium balance studies, biochemical analyses, ground-based simulation models of weightlessness (bed rest, restraint, immobilization) and the planning of inflight experiments. Several animal models have been proposed in the biomedical research literature, but have inherent deficiencies. The purpose of this project was to evaluate models in the literature and determine which of these most closely simulates the phenomenon of bone loss in humans with regard to growth, bone remodeling, structural, chemical and mineralization similarities to human. This was accomplished by a comprehensive computer assisted literature search and report. Three animal models were examined closely for their relative suitability: the albino rat, monkey, and Beagle.

Wolinsky, I.↗

NASA NTRS1987

Bone density in limb-immobilized beagles: An animal model for bone loss in weightlessness

Prolonged weightlessness is man in space flight results in a slow progressive demineralization of bone accompanied by an increased calcium output in the urine resulting in negative calcium balances. This possibly irreversible bone loss may constitute a serious limiting factor to long duration manned space flight. In order to seek and test preventative measures an appropriate ground based animal model simulating weightlessness is necessary. Use of the mature Beagle in limb immobilization has been documented as an excellent model for orthopedic research since this animal most closely simulates the phenomenom of bone loss with regards to growth, remodeling, structure, chemistry and mineralization. The purpose of this project is to develop a research protocol for the study of bone loss in Beagles during and after cast immobilization of a hindleg; research will then be initiated.

Wolinsky, Ira↗

NASA NTRS2005

Exercise and pharmacological countermeasures for bone loss during long-duration space flight

Bone loss in the lower extremities and lumbar spine is an established consequence of long-duration human space flight. Astronauts typically lose as much bone mass in the proximal femur in 1 month as postmenopausal women on Earth lose in 1 year. Pharmacological interventions have not been routinely used in space, and countermeasure programs have depended solely upon exercise. However, it is clear that the osteogenic stimulus from exercise has been inadequate to maintain bone mass, due to insufficient load or duration. Attention has therefore been focused on several pharmacological interventions that have been successful in preventing or attenuating osteoporosis on Earth. Anti-resorptives are the class of drugs most commonly used to treat osteoporosis in postmenopausal women, notably alendronate sodium, risedronate sodium, zoledronic acid, and selective estrogen receptor modulators, such as raloxifene. There has also been considerable recent interest in anabolic agents such as parathyroid hormone (PTH) and teriparatide (rhPTH [1-34]). Vitamin D and calcium supplementation have also been used. Recent studies of kindreds with abnormally high bone mineral density have provided insight into the genetic regulation of bone mass. This has led to potential therapeutic interventions based on the LRP5, Wnt and BMP2 pathways. Another target is the RANK-L/osteoprotegerin signaling pathway, which influences bone turnover by regulating osteoclast formation and maturation. Trials using such therapies in space are being planned. Among the factors to be considered are dose-response relationships, bone quality, post-use recovery, and combination therapies--all of which may have unique characteristics when the drugs are used in space.

NASA Discipline Musculoskeletal↗

NASA NTRS2005

Vitamin E provides protection for bone in mature hindlimb unloaded male rats

The deleterious effects of skeletal unloading on bone mass and strength may, in part, result from increased production of oxygen-derived free radicals and proinflammatory cytokines. This study was designed to evaluate the ability of vitamin E (alpha-tocopherol), a free-radical scavenger with antiinflammatory properties, to protect against bone loss caused by skeletal unloading in mature male Sprague-Dawley rats. A 2 x 3 factorial design was used with either hindlimb unloading (HU) or normal loading (ambulatory; AMB), and low-dose (LD; 15 IU/kg diet), adequate-dose (AD; 75 IU/kg diet), or high-dose (HD; 500 IU/kg diet) vitamin E (DL-alpha-tocopherol acetate). To optimize the effects of vitamin E on bone, dietary treatments were initiated 9 weeks prior to unloading and continued during the 4-week unloading period, at which time animals were euthanized and blood and tissue samples were collected. Serum vitamin E was dose-dependently increased, confirming the vitamin E status of animals. The HD treatment improved oxidation parameters, as indicated by elevated serum ferric-reducing ability and a trend toward reducing tissue lipid peroxidation. Histomorphometric analysis of the distal femur revealed significant reductions in trabecular thickness (TbTh), double-labeled surface (dLS/BS), and rate of bone formation to bone volume (BFR/BV) due by HU. AMB animals on the HD diet and HU animals on the LD diet had reduced bone surface normalized to tissue volume (BS/TV) and trabecular number (TbN); however, the HD vitamin E protected against these changes in the HU animals. Our findings suggest that vitamin E supplementation provides modest bone protective effects during skeletal unloading.

NASA Discipline Musculoskeletal↗

NASA NTRS2001

Spectroscopic characterization of collagen cross-links in bone

Collagen is the most abundant protein of the organic matrix in mineralizing tissues. One of its most critical properties is its cross-linking pattern. The intermolecular cross-linking provides the fibrillar matrices with mechanical properties such as tensile strength and viscoelasticity. In this study, Fourier transform infrared (FTIR) spectroscopy and FTIR imaging (FTIRI) analyses were performed in a series of biochemically characterized samples including purified collagen cross-linked peptides, demineralized bovine bone collagen from animals of different ages, collagen from vitamin B6-deficient chick homogenized bone and their age- and sex-matched controls, and histologically stained thin sections from normal human iliac crest biopsy specimens. One region of the FTIR spectrum of particular interest (the amide I spectral region) was resolved into its underlying components. Of these components, the relative percent area ratio of two subbands at approximately 1660 cm(-1) and approximately 1690 cm(-1) was related to collagen cross-links that are abundant in mineralized tissues (i.e., pyridinoline [Pyr] and dehydrodihydroxylysinonorleucine [deH-DHLNL]). This study shows that it is feasible to monitor Pyr and DHLNL collagen cross-links spatial distribution in mineralized tissues. The spectroscopic parameter established in this study may be used in FTIRI analyses, thus enabling the calculation of relative Pyr/DHLNL amounts in thin (approximately 5 microm) calcified tissue sections with a spatial resolution of approximately 7 microm.

Non-NASA Center↗