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At least 55 records · Page 3

Protein turnover in atrophying muscle: from nutritional intervention to microarray expression analysis

PURPOSE OF REVIEW: In response to decreased usage, skeletal muscle undergoes adaptive reductive remodeling due to the decrease in tension on the weight bearing components of the musculo-skeletal system. This response occurs with uncomplicated disuse (e.g. bed rest, space flight), as a secondary consequence of several widely prevalent chronic diseases for which activity is reduced (e.g. chronic obstructive pulmonary disease and chronic heart failure) and is part of the aging process. The problem is therefore one of considerable clinical importance. RECENT FINDINGS: The impaired function and exercise intolerance is related more to the associated muscle wasting rather than to the specific organ system primarily impacted by the disease. Progress has continued in describing the use of anabolic drugs and dietary manipulation. The major advance in the field has been: (i) the discovery of the atrogin-1 gene and (ii) the application of microarray expression analysis and proteomics with the objectives of obtaining comprehensive understanding of the pathways changed with disuse atrophy. SUMMARY: Disuse atrophy is a common clinical problem. There is a need for therapeutic interventions that do not involve exercise. A better understanding of the changes, particularly at the molecular level, could indicate hitherto unsuspected sites for nutritional and pharmacological intervention.

Non-NASA Center↗

Cardiovascular and sympathetic neural responses to handgrip and cold pressor stimuli in humans before, during and after spaceflight

Astronauts returning to Earth have reduced orthostatic tolerance and exercise capacity. Alterations in autonomic nervous system and neuromuscular function after spaceflight might contribute to this problem. In this study, we tested the hypothesis that exposure to microgravity impairs autonomic neural control of sympathetic outflow in response to peripheral afferent stimulation produced by handgrip and a cold pressor test in humans. We studied five astronauts approximately 72 and 23 days before, and on landing day after the 16 day Neurolab (STS-90) space shuttle mission, and four of the astronauts during flight (day 12 or 13). Heart rate, arterial pressure and peroneal muscle sympathetic nerve activity (MSNA) were recorded before and during static handgrip sustained to fatigue at 40 % of maximum voluntary contraction, followed by 2 min of circulatory arrest pre-, in- and post-flight. The cold pressor test was applied only before (five astronauts) and during flight (day 12 or 13, four astronauts). Mean (+/- S.E.M.) baseline heart rates and arterial pressures were similar among pre-, in- and post-flight measurements. At the same relative fatiguing force, the peak systolic pressure and mean arterial pressure during static handgrip were not different before, during and after spaceflight. The peak diastolic pressure tended to be higher post- than pre-flight (112 +/- 6 vs. 99 +/- 5 mmHg, P = 0.088). Contraction-induced rises in heart rate were similar pre-, in- and post-flight. MSNA was higher post-flight in all subjects before static handgrip (26 +/- 4 post- vs. 15 +/- 4 bursts min(-1) pre-flight, P = 0.017). Contraction-evoked peak MSNA responses were not different before, during, and after spaceflight (41 +/- 4, 38 +/- 5 and 46 +/- 6 bursts min(-1), all P > 0.05). MSNA during post-handgrip circulatory arrest was higher post- than pre- or in-flight (41 +/- 1 vs. 33 +/- 3 and 30 +/- 5 bursts min(-1), P = 0.038 and 0.036). Similarly, responses of MSNA and blood pressure to the cold pressor test were well maintained in-flight. We conclude that modulation of muscle sympathetic neural outflow by muscle metaboreceptors and skin nociceptors is preserved during short duration spaceflight.

NASA Discipline Neuroscience↗

Development of an advanced rocket propellant handler's suit

Most launch vehicles and satellites in the US inventory rely upon the use of hypergolic rocket propellants, many of which are toxic to humans. These fuels and oxidizers, such as hydrazine and nitrogen tetroxide have threshold limit values as low as 0.01 PPM. It is essential to provide space workers handling these agents whole body protection as they are universally hazardous not only to the respiratory system, but the skin as well. This paper describes a new method for powering a whole body protective garment to assure the safety of ground servicing crews. A new technology has been developed through the small business innovative research program at the Kennedy Space Center. Currently, liquid air is used in the environmental control unit (ECU) that powers the propellant handlers suit (PHE). However, liquid air exhibits problems with attitude dependence, oxygen enrichment, and difficulty with reliable quantity measurement. The new technology employs the storage of the supply air as a supercritical gas. This method of air storage overcomes all of three problems above while maintaining high density storage at relatively low vessel pressures (<7000 kPa or approximately 1000 psi). A one hour prototype ECU was developed and tested to prove the feasibility of this concept. This was upgraded by the design of a larger supercritical dewar capable of holding 7 Kg of air, a supply which provides a 2 hour duration to the PHE. A third version is being developed to test the feasibility of replacing existing air cooling methodology with a liquid cooled garment for relief of heat stress in this warm Florida environment. Testing of the first one hour prototype yielded data comparable to the liquid air powered predecessor, but enjoyed advantages of attitude independence and oxygen level stability. Thermal data revealed heat stress relief at least as good as liquid air supplied units. The application of supercritical air technology to this whole body protective ensemble marked an advancement in the state-of-the-art in personal protective equipment. Not only was long duration environmental control provided, but it was done without a high pressure vessel. The unit met human performance needs for attitude independence, oxygen stability and relief of heat stress. This supercritical air (and oxygen) technology is suggested for microgravity applications in life support such as the Extravehicular Mobility Unit. c 2001. Elsevier Science Ltd. All rights reserved.

Hazardous Substances↗

Work capacity and metabolic and morphologic characteristics of the human quadriceps muscle in response to unloading

The response of skeletal muscle to unweighting was studied in six healthy males who were subjected to four weeks of lowerlimb suspension. They performed three bouts of 30 consecutive maximal concentric knee extensions, before unloading and the day after (POST 1), 4 days after (POST 2) and 7 weeks after (REC) resumed weight-bearing. Peak torque of each contraction was recorded and work was calculated as the mean of the average peak torque for the three bouts and fatigability was measured as the decline in average peak torque over bouts. Needle biopsies were obtained from m. vastus lateralis of each limb before and at POST 1. Muscle fibre type composition and area, capillarity and the enzyme activities of citrate synthase (CS) and phosphofructokinase (PFK) were subsequently analysed. Mean average peak torque for the three bouts at POST1, POST2 and REC was reduced (P < 0.05) by 17, 13 and 7%, respectively. Fatigability was greater (P < 0.05) at POST2 than before unloading. Type I, IIA and IIB percentage, Type I and II area and capillaries per fibre of Type I and II did not change (P > 0.05) in response to unloading. The activity of CS, but not PFK, decreased (P < 0.05) after unloading. The weight-bearing limb showed no changes in the variables measured. The results of this study suggest that this human lowerlimb suspension model produces substantial impairments of work and oxidative capacity of skeletal muscle. The performance decrements are most likely induced by lack of weight-bearing.

NASA Center KSC↗

+Gz tolerance in man after 14-day bedrest periods with isometric and isotonic exercise conditioning

The effects of isometric and isotonic exercise training on post-bedrest +Gz tolerance were determined. In general, 14-day bedrest resulted in a significant loss of Gz tolerance, as previously discovered. At 2.1 Gz, neither the isometric nor the isotonic exercises regimens resulted in a significant increase in post-bedrest Gz tolerance. However, following isometric exercise, restoration of about half the tolerance decrement occurred at 3.2 Gz and 3.8 Gz. Possible reasons for this partial restoration of tolerance are put forward.

Greenleaf, J. E.↗

The Gravity of LBNP Exercise: Lessons Learned from Identical Twins in Bed for 30 Days

Microgravity leads to cardiovascular deconditioning in humans, which is manifested by post-flight reduction of orthostatic tolerance and upright exercise capacity. During upright posture on Earth, blood pressures are greater in the feet than at heart or head levels due to gravity's effects on columns of blood in the body. During exposure to Microgravity, all gravitational blood pressures disappear. Presently, there is no exercise hardware available for space flight to provide gravitational blood pressures to tissues of the lower body. We hypothesized that 40 minutes of supine treadmill running per day in a LBNP chamber at 1.0 to 1.2 body weight (approximately 50 - 60 mm Hg LBNP) with a 5 min resting, nonexercise LBNP exposure at 50 mm Hg after the exercise session will maintain aerobic fitness orthostatic tolerance, and selected parameters of musculoskeletal function during 30 days of bed rest (simulated microgravity). This paper is an interim report of some of our findings on 16 subjects.

Hargens, Alan R.↗

Comparing the effects of two in-flight aerobic exercise protocols on standing heart rates and VO(2peak) before and after space flight

The effects of regular aerobic exercise on orthostatic tolerance have been the subject of a long-standing controversy that will influence the use of exercise during space flight. To examine these effects, astronauts performed continuous (CE) aerobic exercise (n = 8), interval (IE) aerobic exercise (n = 4), or no (NE) exercise (n = 5) during flights of 7 to 11 days. Heart rate (HR) responses to an orthostatic challenge (stand test) were measured 10 days before flight and on landing day. VO(2peak) (graded treadmill exercise) was measured 7 to 21 days before and 2 days after flight. No significant differences across the groups were observed in standing HRs before or after flight. However, the within-group mean HRs significantly increased in the NE (71-89 beats/min) and CE (60-85 beats/min) groups after space flight. The HRs for the IE group did not significantly increase (75-86 beats/min) after space flight. VO(2peak) decreased (P < .05) in the NE (-9.5%) group, but did not change in the CE (-2.4%) and IE (1%) groups. The relationship (r = 0.237) between the delta HR and delta VO(2peak) was not significant. These preliminary results indicate that: (1) continuous exercise does not affect the orthostatic HR response after space flight; (2) interval exercise may minimize an increase in the postflight orthostatic HR; and (3) both exercise protocols can maintain VO(2peak).

NASA Discipline Musculoskeletal↗

Exercise thermoregulation - Possible effects of spaceflight

Changes in thermoregulation during spaceflight could result in an inability to tolerate ambient conditions or exercise tasks that were readily tolerated preflight. Weightlessness may alter heat production by changing metabolic rate, circadian rhythms of heat production, or work efficiency. It may impair heat loss by reducing convective and evaporative heat exchange. In addition, crewmembers may become less fit, less heat acclimated, hypohydrated, or have altered thermal sensitivity. Three scenarios are described: exercise conditioning in the mid deck, EVA, and emergency egress. Each scenario is discussed in terms of potential thermal challenges and possible consequences on crew performance.

Fortney, Suzanne M.↗

Modeling the Fault Tolerant Capability of a Flight Control System: An Exercise in SCR Specification

In life-critical and mission-critical applications, it is important to make provisions for a wide range of contingencies, by providing means for fault tolerance. In this paper, we discuss the specification of a flight control system that is fault tolerant with respect to sensor faults. Redundancy is provided by analytical relations that hold between sensor readings; depending on the conditions, this redundancy can be used to detect, identify and accommodate sensor faults.

Alexander, Chris↗

Orthostatic responses following 30-day bed rest deconditioning with isotonic and isokinetic exercise training

The effects of intensive exercise training on tilt tolerance following deconditioning of astronauts were investigated by studying orthostatic responses of 19 subjects who underwent two intensive exercise-training regimens during 30 days of -6-deg head-down bed rest (BR). Subjects were divided into no-exercise control group, and two exercise groups, one performing isotonic (Quinton ergometer) exercises, the other doing isokinetic (Lido ergometer) exercises. A 60-deg head-up tilt test was administered on the control day 1 and BR day 30; the test was terminated at 60 min or when presyncopal signs and/or symptoms occurred. It was found that exercise training did not affect tilt tolerance significantly.

Greenleaf, J. E.↗

Comparison of Gait During Treadmill Exercise While Supine in Lower Body Negative Pressure (LBNP), Supine with Bungee Resistance and Upright in Normal Gravity

The purpose of this study is to compare footward forces, gait kinematics, and muscle activation patterns (EMG) generated during supine treadmill exercise against LBNP with the same parameters during supine bungee resistance exercise and upright treadmill exercise. We hypothesize that the three conditions will be similar. These results will help validate treadmill exercise during LBNP as a viable technique to simulate gravity during space flight. We are evaluating LBNP as a means to load the musculoskeletal and cardiovascular systems without gravity. Such loading should help prevent physiologic deconditioning during space flight. The best ground-based simulation of LBNP treadmill exercise in microgravity is supine LBNP treadmill exercise on Earth because the supine footward force vector is neither directed nor supplemented by Earth's gravity. Previous results from HR-95 ("Dynamics of footward force and leg intramuscular pressure during exercise against supine LBNP and upright standing in normal gravity") indicate that supine plantar-/dorsiflexion exercise in LBNP at 100 mm Hg produces similar ground reaction forces, musculoskeletal stress, and VO2 to those during upright exercise against Earth's gravity. However, elevations of leg volume and heart rate indicate that cardiovascular stress during 100 mm Hg LBNP exercise exceeds that during 1 g exercise. Therefore, the need arose to reduce the cardiovascular stress of LBNP, while maintaining LBNP-induced reaction forces. To this end, we determined that mild plantar-/dorsiflexion exercise during LBNP significantly improves tolerance to LBNP via musculovenous pumping and sympathoexcitation; more intense exercise such as walking and running may further improve LBNP tolerance. In addition, two methodological advances have permited us to simulate upright 1 g exercise better with supine LBNP exercise. First, a newly-designed waist seal allows decreased levels of LBNP (50-60 mm Hg) to produce a footward force equaling one body weight

Boda, Wanda↗

Effect of Exercise Training and +Gz Acceleration Training on Men

Countermeasures for reduction in work capacity (maximal oxygen uptake and strength) during spaceflight and enhanced orthostatic intolerance during re-entry, landing and egress from the return vehicle are continuing problems. The purpose for this study was to test the hypothesis that passive-acceleration training; supine, interval, exercise plus acceleration training and exercise combined with acceleration training would improve orthostatic tolerance in ambulatory men; and that addition of the aerobic exercise conditioning would not alter this improved tolerance from that of passive-acceleration training. Seven men (24-38 yr) underwent "Passive" training on the Ames human-powered centrifuge (HPC) for 30 min, "Exercise" training on the cycle ergometer with constant +Gz acceleration; and "Combined" exercise training at 40% to 90% of the HPC +Gz(max) exercise level. Maximal supine exercise loads increased significant (P<0.05) by 8.3% (Passive), 12.6% (Exercise), and by 15.4% (Combined) after training, but their post-training maximal oxygen uptakes and maximal heart rates were unchanged. Maximal time to fatigue (endurance) was unchanged with Passive was increased (P<0.05) with Exercise and Combined training. Thus, the exercise in the Exercise and Combined training Phases resulted in greater maximal loads and endurance without effect on maximal oxygen uptake or heart rate. There was a 4% to 6% increase (P<0.05) in all four quadriceps muscle volumes (right and left) after post-Combined training. Resting pre-tilt heart rate was elevated by 12.9% (P<0.05) only after Passive training suggesting that the exercise training attenuated the HR response. Plasma volume (% Delta) was uniformly decreased by 8% to 14% (P<0.05) at tilt-tolerance pre- vs. post-training indicating essentially no effect of training on the level of hypovolemia. Post-training tilt-tolerance time and heart rate were increased (P<0.05) only with Passive training by 37.8% and by 29.1%, respectively. Thus, addition of exercise training appeared to attenuate the increased Passive tilt-tolerance.

Greenleaf, John E.↗

Delay/Disruption Tolerance Networking (DTN) Implementation and Utilization Options on the International Space Station

The International Space Station (ISS) is in an operational configuration and nearing final assembly. With its maturity and diverse payloads onboard, the opportunity exists to extend the orbital lab into a facility to exercise and demonstrate Delay/Disruption Tolerant Networking (DTN). DTN is an end-to-end network service providing communications through environments characterized by intermittent connectivity, variable delays, high bit error rates, asymmetric links and simplex links. The DTN protocols, also known as bundle protocols, provide a store-and-forward capability to accommodate end-to-end network services. Key capabilities of the bundling protocols include: the Ability to cope with intermittent connectivity, the Ability to take advantage of scheduled and opportunistic connectivity (in addition to always up connectivity), Custody Transfer, and end-to-end security. Colorado University at Boulder and the Huntsville Operational Support Center (HOSC) have been developing a DTN capability utilizing the Commercial Generic Bioprocessing Apparatus (CGBA) payload resources onboard the ISS, at the Boulder Payload Operations Center (POC) and at the HOSC. The DTN capability is in parallel with and is designed to augment current capabilities. The architecture consists of DTN endpoint nodes on the ISS and at the Boulder POC, and a DTN node at the HOSC. The DTN network is composed of two implementations; the Interplanetary Overlay Network (ION) and the open source DTN2 implementation. This paper presents the architecture, implementation, and lessons learned. By being able to handle the types of environments described above, the DTN technology will be instrumental in extending networks into deep space to support future missions to other planets and other solar system points of interest. Thus, this paper also discusses how this technology will be applicable to these types of deep space exploration missions.

Holbrook, Mark↗

Temperature Regulation in Crewmembers After a 115-Day Space Flight

Impaired thermoregulation, which has been observed during exercise following bed rest, may significantly impact crewmembers during space flight operations by decreasing exercise capacity and orthostatic tolerance. Impaired temperature regulation would cause higher levels of core temperature, due to an attenuated cutaneous vasodilatory reflex and sweating response, for a given oxygen consumption. Two mate crewmembers of the Mir 18 mission performed supine cycle exercise se (20 min @ 40% and 20 min @ 65% preflight VO2pk) 145 days preflight and 5 days postflight. Core temperature (Tcore) was measured by an ingestible telemetry pill, skin blood flow (SBF) by laser Doppler velocimetry, and sweat rate (SR) by dew point hygrometry. Tcore at the time of test termination was similar (37.8 C) for both subjects before and after flight despite a shorter test duration (40 vs 28-29 minutes) postflight. The slopes of the SBF/Tcore relationship (Subj 1: 396 vs 214; Subj 2: 704 vs 143 Perfusion Unit/degC) and SR/Tcore relationship (Subj 1: 4.5 vs 2.1; Subj 2: 11.0 vs 3.6mg/min/sq cm/degC) were reduced postflight. Tcore thresholds for both SR (Subj 1: 37.4 vs 37.6; Subj 2: 37.6 vs 37.6 C) and SBF (Subj 1: 37.3 vs 37.5; Subj 2: 37.6 vs 37.7 C) were similar pre- to postflight. For these 2 crewmembers, it appeared that thermoregulation during exercise was impaired as evidenced by compromised heat loss responses after long-duration space flight.

Lee, S. M. C.↗

Exercise Versus +Gz Acceleration Training

Decreased working capacity and "orthostatic" intolerance are two major problems for astronauts during and after landing from spaceflight in a return vehicle. The purpose was to test the hypotheses that (1) supine-passive-acceleration training, supine-interval-exercise plus acceleration training, and supine exercise plus acceleration training will improve orthostatic tolerance (OT) in ambulatory men; and that (2) addition of aerobic exercise conditioning will not influence this enhanced OT from that of passive-acceleration training. Seven untrained men (24-38 yr) underwent 3 training regimens (30 min/d x 5d/wk x 3wk on the human-powered centrifuge - HPC): (a) Passive acceleration (alternating +1.0 Gz to 50% Gzmax); (b) Exercise acceleration (alternating 40% - 90% V02max leg cycle exercise plus 50% of HPCmax acceleration); and (c) Combined intermittent exercise-acceleration at 40% to 90% HPCmax. Maximal supine exercise workloads increased (P < 0.05) by 8.3% with Passive, by 12.6% with Exercise, and by 15.4% with Combined; but maximal V02 and HR were unchanged in all groups. Maximal endurance (time to cessation) was unchanged with Passive, but increased (P < 0.05) with Exercise and Combined. Resting pre-tilt HR was elevated by 12.9% (P < 0.05) only after Passive training, suggesting that exercise training attenuated this HR response. All resting pre-tilt blood pressures (SBP, DBP, MAP) were not different pre- vs. post-training. Post-training tilt-tolerance time and HR were increased (P < 0.05) only with Passive training by 37.8% and by 29.1%, respectively. Thus, addition of exercise training attenuated the increased Passive tilt tolerance. Resting (pre-tilt) and post-tilt cardiac R-R interval, stroke volume, end-diastolic volume, and cardiac output were all uniformly reduced (P < 0.05) while peripheral resistance was uniformly increased (P < 0.05) pre-and post-training for the three regimens indicating no effect of any training regimen on those cardiovascular variables. Plasma volume (% delta) was uniformly decreased by 8% to 14% (P < 0.05) at tilt-tolerance pre- vs. post-training for all regimens indicating no effect of these training regimens on the level of vascular fluid shifts.

Greenleaf, John E.↗

Application of Acute Maximal Exercise to Enhance Mechanisms Underlying Blood Pressure Regulation and Orthostatic Tolerance After Exposure to Simulated Microgravity

Development of orthostatic hypotension and intolerance in astronauts who return to earth following a spaceflight mission represents a significant operational concern to NASA. Reduced plasma volume, vascular resistance, and baroreflex responsiveness following exposure to actual and ground-based analogs of microgravity have been associated with orthostatic instability, suggesting that these mechanisms may contribute alone or in combination to compromise of blood pressure regulation after spaceflight. It therefore seems reasonable that development of procedures designed to reverse or restore the effects of microgravity on regulatory mechanisms of blood volume, vascular resistance and cardiac function should provide some protection against postflight orthostatic intolerance. Several investigations have provided evidence that a single bout of exhaustive dynamic exercise enhances functions of mechanisms responsible for blood pressure stability. Therefore, the purpose of our research project was to conduct a series of experiments using ground-based analogs of reduced gravity (i.e., prolonged restriction to the upright standing posture) in human subjects to investigate the hypothesis that a single bout of dynamic maximal exercise would restore blood volume, vascular resistance and cardiac function and improve blood pressure stability.

Convertino, V. A.↗

Excercise Within LBNP as an Artificial Gravity Countermeasure

Previous exercise in space has lacked sufficient loads to maintain preflight cardiovascular and musculoskeletal mass and function. Lower body negative pressure (LBNP) produces a static force equivalent to one Earth body weight by each 52 mm Hg of LBNP during supine posture. LBNP also provides transmural blood pressures simulating upright exercise. Thus, this artificial-gravity concept may help maintain cardiovascular and musculoskeletal systems of crewmembers during prolonged exposure to microgravity. Currently available, bungee cord assisted, treadmill exercise is limited by harness discomfort, lower than normal loads, abnormal post-flight gait, and the absence of gravitational blood pressures within the vascular system. PURPOSE: This project evaluates a method to create artificial gravity using supine LBNP treadmill exercise to prevent loss of physiologic function in microgravity simulated by 30 days of bed rest. Identical twins were used as volunteers so that statistical power could be maximized. This countermeasure is being transitioned to space flight. CURRENT STATUS OF RESEARCH Methods: Six sets of identical twins (6 females and 14 males, 21-36 years) remained in 6 head-down tilt (HDT) bed rest for 30 days to simulate prolonged microgravity. Six subjects were randomly selected to exercise supine in an LBNP chamber for 40 minutes six days per week (EX group), while their twin brothers served as non-exercise controls (CON). Pressure within the exercise LBNP chamber was adjusted to increase load, hence increasing exercise intensity. During supine treadmill exercise, LBNP (52-63 mmHg) was applied to produce foot ward forces equivalent to those for upright running on Earth at 1.0-1.2 times body weight (BW) and subjects performed an interval exercise protocol (40-80% peak exercise capacity [VO2pk]). Five minutes of resting LBNP immediately followed each exercise session. Results: Orthostatic tolerance time decreased significantly after 30 days bed rest in the CON group, but was relatively maintained in the EX group. VO2pk was maintained in EX males, but not in CON males. Isokinetic knee strength (extension, peak torque) decreased significantly in CON males, but was preserved in EX males. The EX group had significantly higher spine muscle strength after bed rest than the CON group. The cross-sectional area of spinal muscle at L4/5 level decreased significantly in the CON group but not in the EX group. Urinary n-telopeptide excretion, an index of bone resorption, was increased during bed rest in CON, but not in EX subjects. This suggests protection by LBNP exercise against the increase in bone resorption typically seen in simulated and actual microgravity. Significant changes in bone mineral density (BMD) in the spine and ribs were observed in CON subjects, but not in EX subjects. Conclusions: Our treadmill exercise protocol within LBNP plus a short period of post-exercise LBNP maintains orthostatic responses, upright exercise capacity and other important physiologic parameters during bed rest. These results document the efficacy of our apparatus and exercise protocol for maintaining physiologic structure and function during long-duration microgravity as simulated by 30 days of HDT bed rest. FUTURE PLANS: More sets of female identical twins are needed to reach significance. The LBNP exercise chamber will be redesigned for flight.

Hargens, A. R.↗