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At least 73 records · Page 4

Molecular events underlying skeletal muscle atrophy and the development of effective countermeasures

Skeletal muscle adapts to loading; atrophying when exposed to unloading on Earth or in spaceflight. Significant atrophy (decreases in muscle fiber cross-section of 11-24%) in humans has been noted after only 5 days in space. Since muscle strength is determined both by muscle cross-section and synchronization of motor unit recruitment, a loss in muscle size weakens astronauts, which would increase risks to their safety if an emergency required maximal muscle force. Numerous countermeasures have been tested to prevent atrophy. Resistant exercise together with growth hormone and IGF-I are effective countermeasures to unloading as most atrophy is prevented in animal models. The loss of muscle protein is due to an early decrease in protein synthesis rate and a later increase in protein degradation. The initial decrease in protein synthesis is a result of decreased protein translation, caused by a prolongation in the elongation rate. A decrease in HSP70 by a sight increase in ATP may be the factors prolonging elongation rate. Increases in the activities of proteolytic enzymes and in ubiquitin contribute to the increased protein degradation rate in unloaded muscle. Numerous mRNA concentrations have been shown to be altered in unloaded muscles. Decreases in mRNAs for contractile proteins usually occur after the initial fall in protein synthesis rates. Much additional research is needed to determine the mechanism by which muscle senses the absence of gravity with an adaptive atrophy. The development of effective countermeasures to unloading atrophy will require more research.

Non-NASA Center↗

Effects of a 33-Ion Sequential Beam Galactic Cosmic Ray Analog on Male Mouse Behavior and Evaluation of CDDO-EA as a Radiation Countermeasure

In long-term spaceflight, astronauts will face unique cognitive loads and social challenges which will be complicated by communication delays with Earth. It is important to understand the central nervous system (CNS) effects of deep spaceflight and the associated unavoidable exposure to galactic cosmic radiation (GCR). Rodent studies show single- or simple-particle combination exposure alters CNS endpoints, including hippocampal-dependent behavior. An even better Earth-based simulation of GCR is now available, consisting of a 33-beam (33-GCR) exposure. However, the effect of whole-body 33-GCR exposure on rodent behavior is unknown, and no 33-GCR CNS countermeasures have been tested. Here astronaut-age-equivalent (6mo-old) C57BL/6J male mice were exposed to 33-GCR (75cGy, a Mars mission dose). Pre-/during/post-Sham or 33-GCR exposure, mice received a diet containing a ‘vehicle’ formulation alone or with the antioxidant/anti-inflammatory compound CDDO-EA as a potential countermeasure. Behavioral testing beginning 4mo post-irradiation suggested radiation and diet did not affect measures of exploration/anxiety-like behaviors (open field, elevated plus maze) or recognition of a novel object. However, in 3-Chamber Social Interaction (3-CSI), CDDO-EA/33-GCR mice failed to spend more time exploring a holder containing a novel mouse vs. a novel object (empty holder), suggesting sociability deficits. Also, Vehicle/33-GCR and CDDO-EA/Sham mice failed to discriminate between a novel stranger vs. familiarized stranger mouse, suggesting blunted preference for social novelty. CDDO-EA given pre-/ during/post-irradiation did not attenuate the 33-GCR-induced blunting of preference for social novelty. Future elucidation of the mechanisms underlying 33-GCR-induced blunting of preference for social novelty will improve risk analysis for astronauts which may in-turn improve countermeasures.

Space radiation↗

Effects of A 33-Ion Sequential Beam Galactic Cosmic Ray Analog on Male Mouse Behavior and Evaluation of CDDO-EA as A Radiation Countermeasure

In long-term spaceflight, astronauts will face unique cognitive loads and social challenges which will be complicated by communication delays with Earth. It is important to understand the central nervous system (CNS) effects of deep spaceflight and the associated unavoidable exposure to galactic cosmic radiation (GCR). Rodent studies show single- or simple-particle combination exposure alters CNS endpoints, including hippocampal-dependent behavior. An even better Earth-based simulation of GCR is now available, consisting of a 33-beam (33-GCR) exposure. However, the effect of whole-body 33-GCR exposure on rodent behavior is unknown, and no 33-GCR CNS countermeasures have been tested. Here astronaut-age-equivalent (6mo-old) C57BL/6J male mice were exposed to 33-GCR (75cGy, a Mars mission dose). Pre-/during/post-Sham or 33-GCR exposure, mice received a diet containing a ‘vehicle’ formulation alone or with the antioxidant/anti-inflammatory compound CDDO-EA as a potential countermeasure. Behavioral testing beginning 4mo post-irradiation suggested radiation and diet did not affect measures of exploration/anxiety-like behaviors (open field, elevated plus maze) or recognition of a novel object. However, in 3-Chamber Social Interaction (3-CSI), CDDO-EA/33-GCR mice failed to spend more time exploring a holder containing a novel mouse vs. a novel object (empty holder), suggesting sociability deficits. Also, Vehicle/33-GCR and CDDO-EA/Sham mice failed to discriminate between a novel stranger vs. familiarized stranger mouse, suggesting blunted preference for social novelty. CDDO-EA given pre-/ during/post-irradiation did not attenuate the 33-GCR-induced blunting of preference for social novelty. Future elucidation of the mechanisms underlying 33-GCR-induced blunting of preference for social novelty will improve risk analysis for astronauts which may in-turn improve countermeasures.

Space radiation↗

Countermeasures to microgravity

Biological systems ranging from the most simple to the most complex generally survive exposure to microgravity. Changes in many characteristics of biological systems are well documented as a consequence of space flight. Attempts to devise countermeasures to microgravity may have direct pragmatic consequences for crew protection and may provide additional insights into the nature of microgravity influences on biological systems. Some of the most well documented changes occur in humans who have experienced space flight. Changes appear to be transient. Space adaption syndrome occurs relatively briefly whereas bone deterioration may require months of postflight time for restoration. It seems critical to recognize that these changes and others may derive from rather passive, active or even reactive changes in the biological systems that are hosts to them. For example, hydrostatic fluid redistributions may be quite passive occurrences that are realized through extensive fluid channels. Changes occur in cell metabolism because of fluid, nutrient and gas redistributions. Equally important are the misconstrued messages likely to be carried by fluid redistributions. These reactive events can trigger, for example, loss of fluids and electrolytes through altered kidney function. Each of these considerations must be evaluated in regard to the biological site affected. Countermeasures to the vast range of biological changes and sites are difficult to envision. The most obvious countermeasure is the restoration of gravity-like influences. Some options are discussed. Recent work has focussed on the use of magnetic fields. Pulsed electromagnetic fields (PEMF) are shown to alleviate bone deterioration produced in rodents exposed to tail suspension. Methods of PEMF exposure are consistent with human use in space. Related methods may provide muscular and neural benefits.

Luttges, Marvin W.↗

Effect of fluid countermeasures of varying osmolarity on cardiovascular responses to orthostatic stress

Current operational procedures for shuttle crewmembers include the ingestion of a fluid countermeasure approximately 2 hours before reentry into the earth's gravitational field. The ingestion of the fluid countermeasure is thought to restore plasma volume and improve orthostatic responses upon reentry. The present countermeasure consists of ingesting salt tablets and water to achieve an isotonic solution. It has yet to be determined whether this is the optimal drink to restore orthostatic tolerance. It is also not known whether the drink solution is effective in increasing plasma volume. The purpose here is to evaluate the effectiveness of drink solutions of different osmolarity on restoring plasma volume and orthostatic responses. A hypertonic drink solution was more effective in restoring plasma volume after dehydration than an isotonic solution. However, there were no differences in their effects on an orthostatic challenge. These data suggest that the plasma volume differences produced in this study were not sufficient to produce differences in the cardiovascular responses to an orthostatic challenge, or there are other changes that occur during space flight that are more important in determining orthostatic intolerance.

Davis, John E.↗

Centrifugal intensity and duration as countermeasures to soleus muscle atrophy

The effects of artificially induced gravity on the atrophy process of slow-twitch soleus muscle are studied in order to determine whether centrifugation could be an effective countermeasure to nonweight bearing at 1 G. It is observed that the soleus muscle atrophied 32 percent during seven days of nonweight bearing without countermeasures, and centrifugation treatment did not completely prevent atrophy relative to precontrol wet weight of the soleus muscle. Nonweight-bearing groups receiving treatments of 1, 1.5, or 2.6 G had 48, 56, and 65 percent, respectively, of the atrophy observed in a nonweight-bearing-only group compared with the precontrol group. It is concluded that, as a countermeasure to nonweight-bearing-induced atrophy of the soleus muscle, centrifugation at 2.6 G is no more effective than exposure to 1 or 1.5 G.

D'Aunno, Dominick S.↗

Development of countermeasures for medical problems encountered in space flight

Past experience with piloted space missions is reviewed to develop potential countermeasures to the medical problems associated with a long-duration space flight. Particular attention is given to the Extended Duration Orbiter Medical Program, which is aimed at ensuring crew health and safety on Space Shuttle missions; Soviet experience with long-duration space flights; and a variety of countermeasures including physiological, psychological, environmental health, radiation protection, and artificial gravity countermeasures.

Nicogossian, Arnauld E.↗

Countermeasures against space flight related bone loss

A general review is presented of data on bone loss with references to countermeasures for use during spaceflight and bedrest. The two primary countermeasures against skeletal atrophy are skeletal loading such as centrifugation and exercise and/or the administration of drugs designed to alter the rate of bone remodeling. Bone loss is argued to be unavoidable in long-duration spaceflight in spite of countermeasures utilized, but a combination of exercise, biochemical treatments, and post-flight therapy is considered the optimal solution.

Leblanc, Adrian↗

The value of the 4-day headdown bedrest model for screening countermeasures

In order to evaluate the benefits of periodic exposure to the +G(z) vector as a countermeasure to the physiological responses to minus 6 degree head down bedrest (HDT), we considered a two-tiered approach: (a) to use 4 days HDT as a quick and inexpensive means of screening countermeasures, (b) to use a 60 day HDT to validate the most promising candidates. The approach and results of a 4 day study are described here. Methods: Nine males were admitted to our Human Research Facility for one ambulatory control day followed by 4 days HDT and were released on the next day after completion of a peak oxygen consumption test (VO(sub 2 peak)). A battery of tests was selected and standardized to evaluate the known early effects of HDT on plasma volume, early bone markers, orthostatic tolerance, physical performance, and fluid and electrolytes and their hormone regulation. Fluid sodium (Na) and potassium (K) intake and output in the urine were monitored throughout. Plasma volume was determined with a modified Evans Blue method and orthostatic tolerance with a 60 degree head-up tilt test for 30 minutes - both of which were determined on the ambulatory control day and on day 4 of HDT. Immediately after completion of the tilt test subjects were returned to the minus 6 degree position until the next morning when a VO(sub 2 peak) (horizontal ergometer) was done. This was compared to a similar control test determined on 2 separate occasions before subject admission. Results: Four hours after going HDT produced significant decreases (p less than 0.05) in the circulating concentration of fluid and electrolyte regulating hormones. Plasma volume, orthostatic tolerance and VO(sub 2 peak) changed significantly after 4 days HDT. There was also the expected natriuresis on day 1 of HDT but no significant diuresis. The consistency of the pre-bedrest VO(sub 2 peak) tilt tests and plasma volumes was remarkable. Conclusions: The 4 day HDT model seems highly promising for screening a variety of countermeasures alone and in combination before validating their benefits in extended bedrest or flight experiments.

Vernikos, J.↗

Countermeasure development to space adaptation

At the Johnson Space Center we are actively involved, with the collaboration of other NASA Centers and the scientific community at large, in the search for ways to counter the negative affects of spaceflight beginning with the improvement in our understanding of the adaptation. Heretofore this search will be broadly referred to as countermeasures development and includes not only the preservation of physiological well-being but also pyschological well-being. The psychological integrity of crews will, undoubtedly, become progressively more important as lengths, remoteness, and risks of missions increase. The character and priorities of our contermeasure development is very much dependent upon the character of the mission and requires a very close liaison between Medical Operations and the investigators. Because of the demands which countermeasure implementation imposes upon crew schedules and because of the potential weight, power, and budget impacts of the hardware and its development, a countermeasure can only become operational when it is either adequately validated or the human risk of not applying the existing technology exceeds the other negative impacts not directly related to crew health and safety.

Larochelle, F. T.↗

Exercise Countermeasures Demonstration Project During the Lunar-Mars Life Support Test Project Phase 2A

This demonstration project assessed the crew members' compliance to a portion of the exercise countermeasures planned for use onboard the International Space Station (ISS) and the outcomes of their performing these countermeasures. Although these countermeasures have been used separately in other projects and investigations, this was the first time they'd been used together for an extended period (60 days) in an investigation of this nature. Crew members exercised every day for six days, alternating every other day between aerobic and resistive exercise, and rested on the seventh day. On the aerobic exercise days, subjects exercised on an electronically braked cycle ergometer using a protocol that has been previously shown to maintain aerobic capacity in subjects exposed to a space flight analogue. On the resistive exercise days, crew members performed five major multijoint resistive exercises in a concentric mode, targeting those muscle groups and bones we believe are most severely affected by space flight. The subjects favorably tolerated both exercise protocols, with a 98% compliance to aerobic exercise prescription and a 91% adherence to the resistive exercise protocol. After 60 days, the crew members improved their peak aerobic capacity by an average 7%, and strength gains were noted in all subjects. These results suggest that these exercise protocols can be performed during ISS, lunar, and Mars missions, although we anticipate more frequent bouts with both protocols for long-duration spaceflight. Future projects should investigate the impact of increased exercise duration and frequency on subject compliance, and the efficacy of such exercise prescriptions.

Lee, Stuart M. C.↗

Bone Loss in Space: Shuttle/MIR Experience and Bed Rest Countermeasure Program

Loss of bone mineral during space flight was documented in the 1970's Skylab missions. The USSR space program made similar observations in the 1980's. The Institute of Biomedical Problems in Moscow and NASA JSC in 1989 began to collect pre- and post-flight bone mineral density (BMD) using Hologic QDR 1000 DEXA scanners transferred from JSC to Moscow and Star City. DEXA whole body, hip, and lumbar spine scans were performed prior to and during the first week after return from 4- to 6-month missions (plus one 8-month mission and one 14- month mission) on the Mir space station. These data documented the extent and regional nature of bone loss during long duration space flight. Of the 18 cosmonauts participating in this study between 1990 and 1995, seven flew two missions. BMD scans prior to the second flight compared to the first mission preflight scans indicated that recovery was possibly delayed or incomplete. Because of these findings, NASA and IBMP initiated the study "Bone Mineral Loss and Recovery After Shuttle/Mir Flights" in 1995 to evaluate bone recovery during a 3-year post-flight period. All of the 14 participants thus far evaluated lost bone in at least one region of the spine and lower extremities during flight. Of the 14, only one to date has exhibited full return to baseline BNM values in all regions. The current study will continue until the last participant has reached full bone recovery in all regions, has reached a plateau, or until three years after the flight (2001 for the last mission of the program). Bone mineral density losses in space and difficulty in returning to baseline indicate a need for countermeasure development. In late 1996 NASA JSC and Baylor College of Medicine were approved to conduct two countermeasure studies during 17 weeks of bed rest. In 1997 the studies were begun in the bed rest facility established by NASA, Baylor College of Medicine, and The Methodist Hospital in Houston. To date, three bed rest controls, five resistive exercisers, and four subjects taking alendronate (a bisphoshonate that inhibits osteoclastic resorption of bone) have completed 17 weeks bed rest. In contrast to information currently available from space flight (n=28) and bed rest (n= 12) in which all individuals experienced bone loss in at least one region, one of four subjects taking alendronate and one of five subjects performing heavy resistive exercise at bed rest fully maintained bone density in all regions of the spine and lower extremities. Overall results of both countermeasures which will be presented are encouraging. The study will be completed by mid to late 2000 with 10 subjects in each of three groups.

Shackelford, L. C.↗

The Biomechanics of Exercise Countermeasures

The Penn State Zero-gravity Simulator (PSZS) is a device developed by the Center for Locomotion Studies (CELOS) to enable ground studies of exercise countermeasures for the bone loss that has been shown to occur during long-term exposure to zero gravity (0G). The PSZS simulates 0G exercise by providing a suspension system that holds an individual in a horizontal (supine) position above the floor in order to enable exercise on a wall-mounted treadmill. Due to this orientation, exercise performed in the PSZS is free of the force of -ravity in the direction that would normally contribute to ground reaction forces. In order for movements to be more similar to those in 0G, a constant force suspension of each segment (equal to the segment weight) is provided regardless of limb position. During the preliminary development of the PSZS, CELOS researchers also designed an optional gravity-replacement simulation feature for the PSZS. This feature was a prototype tethering system that consisted of a spring tension system to pull an exercising individual toward the treadmill. The immediate application of the tethering system was to be the provision of gravity-replacement loading so that exercise in 0G- and 1G-loading conditions could be compared, and the PSZS could then be used to evaluate exercise countermeasures for bone loss during space flight. This tethering system would also be a model for the further refinement of gravity-replacement systems provided for astronaut usage while performing prescribed exercise countermeasures for bone loss during long-term space flights.

Cavanagh, Peter R.↗

Controlled breaks as a fatigue countermeasure on the flight deck

BACKGROUND: A major challenge for flight crews is the need to maintain vigilance during long, highly automated nighttime flights. No system currently exists to assist in managing alertness, and countermeasure options are limited. Surveys reveal many pilots use breaks as an in-flight countermeasure, but there have been no controlled studies of their effectiveness. HYPOTHESIS: We hypothesized that brief, regular breaks could improve alertness and performance during an overnight flight. METHOD: A 6-h, uneventful, nighttime flight in a Boeing 747-400 flight simulator was flown by fourteen two-man crews. The 14 subjects in the treatment group received 5 short breaks spaced hourly during cruise; the 14 subjects in the control group received 1 break in the middle of cruise. Continuous EEG/EOG, subjective sleepiness, and psychomotor vigilance performance data were collected. RESULTS: During the latter part of the night, the treatment group showed significant reductions for 15 min post-break in slow eye movements, theta-band activity, and unintended sleep episodes compared with the control group. The treatment group reported significantly greater subjective alertness for up to 25 min post-break, with strongest effects near the time of the circadian trough. There was no evidence of objective vigilance performance improvement at 15-25 min post-break, with expected performance deterioration occurring due to elevated sleep drive and circadian time. CONCLUSIONS: The physiological and subjective data indicate the breaks reduced nighttime sleepiness for at least 15 min post-break and may have masked sleepiness for up to 25 min, suggesting the potential usefulness of short-duration breaks as an in-flight fatigue countermeasure.

Non-NASA Center↗

A comprehensive Guyton model analysis of physiologic responses to preadapting the blood volume as a countermeasure to fluid shifts

The Guyton model of fluid, electrolyte, and circulatory regulation is an extensive mathematical model capable of simulating a variety of experimental conditions. It has been modified for use at NASA to simulate head-down tilt, a frequently used analog of weightlessness. Weightlessness causes a headward shift of body fluids that is believed to expand central blood volume, triggering a series of physiologic responses resulting in large losses of body fluids. We used the modified Guyton model to test the hypothesis that preadaptation of the blood volume before weightless exposure could counteract the central volume expansion caused by fluid shifts, and thereby attenuate the circulatory and renal responses that result in body fluid losses. Simulation results show that circulatory preadaptation, by a procedure resembling blood donation immediately before head-down bedrest, is effective in damping the physiologic responses to fluid shifts and reducing body fluid losses. After 10 hours of head-down tilt, preadaptation also produces higher blood volume, extracellular volume, and total body water for 20 to 30 days of bedrest, compared with non-preadapted control. These results indicate that circulatory preadaptation before current Space Shuttle missions may be beneficial for the maintenance of reentry and postflight orthostatic tolerance in astronauts. This paper presents a comprehensive examination of the simulation results pertaining to changes in relevant physiologic variables produced by blood volume reduction before a prolonged head-down tilt. The objectives were to study and develop the countermeasure theoretically, to aid in planning experimental studies of the countermeasure, and to identify potentially disadvantageous physiologic responses that may be caused by the countermeasure.

NASA Center JSC↗

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↗

Current ISS Exercise Countermeasures: Where are we now?

Current International Space Station (ISS) crew schedules include 1.5 h/d for completion of resistive exercise and 1 h/d of aerobic exercise , 6 d/wk. While ISS post flight decrements in muscle strength, bone m ineral density, and aerobic capacity improved in some crewmembers, de conditioning was still evident even with this volume of exercise. Res ults from early ISS expeditions show maximum loss in bone mineral density of the lumbar spine and pelvis in excess of 1.5% per month, with all crewmembers demonstrating significant bone loss in one or more re gions. Similarly, post flight muscle strength losses in the hamstring and quadriceps muscle groups exceeded 30% in the immediate post miss ion period in some crewmembers. Measures of aerobic capacity early in the mission show average decrements of 15%, but with onboard aerobic exercise capability, the crew has been able to "train up" over the co urse of the mission. These findings are highly variable among crewmem bers and appear to be correlated with availability and reliability of the inflight resistive exercise device (RED), cycle ergometer, and t readmill. This suite of hardware was installed on ISS with limited op erational evaluation in groundbased test beds. As a result, onorbit hardware constraints have resulted in inadequate physical stimulus, d econditioning, and increased risk for compromised performance during intra and extravehicular activities. These issues indicate that the c urrent ISS Countermeasures System reliability or validity are not ade quate for extendedduration exploration missions. Learning Objective: A better understanding of the status of ISS exercise countermeasures , their ability to protect physiologic systems, and recommendations for exploration exercise countermeasures.

Hayes, J. C.↗

Human Health Countermeasures (HHC) Element Management Plan: Human Research Program

NASA s Human Research Program (HRP) is an applied research and technology program within the Human Exploration and Operations Mission Directorate (HEOMD) that addresses human health and performance risk mitigation strategies in support of exploration missions. The HRP research and technology development is focused on the highest priority risks to crew health and safety with the goal of ensuring mission success and maintaining long-term crew health. Crew health and performance standards, defined by the NASA Chief Health and Medical Officer (CHMO), set the acceptable risk level for exploration missions. The HRP conducts research to inform these standards as well as provide deliverables, such as countermeasures, that ensure standards can be met to maximize human performance and mission success. The Human Health Countermeasures (HHC) Element was formed as part of the HRP to develop a scientifically-based, integrated approach to understanding and mitigating the health risks associated with human spaceflight. These health risks have been organized into four research portfolios that group similar or related risks. A fifth portfolio exists for managing technology developments and infrastructure projects. The HHC Element portfolios consist of: a) Vision and Cardiovascular; b) Exercise and Performance; c) Multisystem; d) Bone; and e) Technology and Infrastructure. The HHC identifies gaps associated with the health risks and plans human physiology research that will result in knowledge required to more fully understand risks and will result in validated countermeasures to mitigate risks.

Norsk, Peter↗