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At least 181 records · Page 10

Effects of long-duration bed rest on structural compartments of m. soleus in man

Magnetic resonance imaging (MRI), histomorphometry and electron microscopy of muscle demonstrate that long-term exposure to actual or simulated weightlessness (including head down bed rest) leads to decreased volume of antigravity muscles in mammals. In muscles interbundle space is occupied by the connective tissue. Rat studies show that hindlimb unloading induces muscle fiber atrophy along with increase in muscle non-fiber connective tissue compartment. Beside that, usually 20% of the muscle fiber volume is comprised by non-contractile (non-myofibrillar) compartment. The aim of the present study was to compare changes in muscle volume, and in muscle fiber size with alterations in myofibrillar apparatus, and in connective tissue compartment in human m. soleus under conditions of 120 day long head down bed rest (HDBR).

Non-NASA Center↗

Effect of leg exercise training on vascular volumes during 30 days of 6 deg head-down bed rest

In order to investigate the effects of leg exercise training on vascular volumes during 30 d of 6-deg head-down bed rest, plasma and red cell volumes, body density, and water balance were measured in 19 men confined to bed rest (BR). One group had no exercise training (NOE), another near-maximal variable-intensity isotonic exercise (ITE) for 60 min/d, and the third near-maximal intermittent isokinetic exercise (IKE) for 60 min/d. Mean energy costs for the NOE, IKE, and ITE regimens were determined. Body densities within groups and mean urine volumes between groups were unchanged during BR. Changes in red cell volume followed changes in plasma volume. There was close coupling between resting plasma volume and plasma protein and osmotic content. It is argued that the ITE training protocol is better than the IKE protocol for maintaining plasma volume during prolonged exposure to BR.

Greenleaf, J. E.↗

B Complex 5-Methyltetrahydrofolate, Riboflavin, Pyridoxine, and Methylcobalamin Supplementation as a Non-Mechanical Countermeasure to Mitigate Optic Disc Edema Changes During Strict 6º Head-Down Tilt Bed Rest

A subset of astronauts on International Space Station missions have experienced optic disc edema, part of what is characterized as Spaceflight Associated Neuro-ocular Syndrome (SANS). While the precise cause of SANS is unknown, it is likely that there are multiple contributing factors, including genetic and environmental factors. Our recent work has shown that crewmembers with SANS have higher concentrations of metabolic biomarkers of impairments in the one-carbon metabolic pathway compared to unaffected astronauts - before, during, and after f light (1). B-vitamin status and the presence of one-carbon pathway single nucleotide polymorphism (SNP) variants predicted the incidence of SANS pathologies, including optic disc edema (2). Specifically, the G allele of methionine synthase reductase (MTRR) A66G and the C allele of serine hydroxymethyltransferase-1 (SHMT1) C1420T were associated with increased incidence of SANS pathologies (2). In a recent 30-d bed rest head-down tilt study with 0.5% CO2 exposure, 5 of 11 subjects developed optic disc edema (4) and the same SHMT1 C1420T and MTRR A66G genetic variants were associated with a larger increase in total retina thickness, a quantitative measure of optic disc edema (5). We published a multi-hit hypothesis of how genetics represents an indispensable element of SANS, which is a multifactorial problem (6). In brief: endothelial dysfunction secondary to genetic, biochemical/nutritional, and physiological (e.g., cardiovascular/fluid shift) f actors could lead to optic disc edema and the other ocular changes that occur in SANS. We expanded this hypothesis to include the possibility that genetic effects on B-vitamin status can alter nitric oxide synthesis and oxidative stress in the endothelium. This in turn could alter the turnover of structural components of the sclera, making it more susceptible to pathologic changes when faced with stressors related to the unrelenting headward fluid shift that occurs in weightlessness and strict head-down tilt bed rest (5). If the relationships that we have observed in flight and ground-based research hold true for the SANS Countermeasure Study, these genetic factors could predict who will be more susceptible to the development of SANS, and more importantly could also provide countermeasure options. As has been shown extensively in the literature, vitamin supplementation can serve to overcome genetic hindrances to one-carbon biochemistry and vascular physiology. Thus, based on our findings, publications, and hypotheses, supported by extensive supporting literature, we had hoped to test in the SANS Countermeasure Study the efficacy of a bioactive B-vitamin complex as a countermeasure to optimize function of the one-carbon pathway and prevent or mitigate optic disc edema during strict 6-degree head down tilt bed rest, and ultimately in space f light. While the supplement is no longer planned to be tested in the SANS Countermeasure Study because of laws regulating supplementation studies like this costing much more than initially planned, we will assess the contribution of one-carbon pathway genetics and B-vitamin status to SANS risk.

S R Zwart↗

Fibroblast Growth Factor-23 in Bed Rest and Spaceflight

Many nutritional factors influence bone, from the basics of calcium and vitamin D, to factors which influence bone through acid/base balance, including protein, sodium, and more. Fibroblast growth factor 23 (FGF23) is a recently identified factor, secreted from osteocytes, which is involved in classic (albeit complex) feedback loops controlling phosphorus homeostasis through both vitamin D and parathyroid hormone (PTH) (1, 2). As osteocytes are gravity sensing cells, it is important to determine if there are changes in FGF23 during spaceflight. In extreme cases, such as chronic kidney disease, FGF23 levels are highly elevated. FGF23 imbalances, secondary to dietary influences, may contribute to skeletal demineralization and kidney stone risk during spaceflight. Presented with an imbalanced dietary phosphorus to calcium ratio, increased secretion of FGF23 will inhibit renal phosphorus reabsorption, resulting in increased excretion and reduced circulating phosphorus. Increased intake and excretion of phosphorus is associated with increased kidney stone risk in both the terrestrial and microgravity environments. Highly processed foods and carbonated beverages are associated with higher phosphorus content. Ideally, the dietary calcium to phosphorus ratio should be at minimum 1:1. Nutritional requirements for spaceflight suggest that this ratio not be less than 0.67 (3), while the International Space Station (ISS) menu provides 1020 mg Ca and 1856 mg P, for a ratio of 0.55 (3). Subjects in NASA's bed rest studies, by design, have consumed intake ratios much closer to 1.0 (4). FGF23 also has an inhibitory influence on PTH secretion and 1(alpha)-hydroxylase, both of which are required for activating vitamin D with the conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. Decreased 1,25-dihydroxyvitamin D will result in decreased intestinal phosphorus absorption, and increased urinary phosphorus excretion (via decreased renal reabsorption). Should a decrease in 1,25- dihydroxyvitamin D be necessary to reduce intestinal phosphorus absorption, calcium absorption will also proportionally be reduced, potentially leading to skeletal demineralization. Demineralization of bone can increase kidney stone risk, a medical issue that could prove detrimental to mission success. Given the interrelationships described above, we sought to determine circulating FGF23 concentrations in spaceflight and ground analog studies to better understand the potential effects of dietary phosphorus on bone and calcium metabolism. We analyzed serum from ISS astronauts participating in studies of bone biochemistry, including the Nutrition SMO and Pro K experiments, and we also evaluated FGF23 during extended-duration bed rest. Serum intact FGF23 levels were determined using an ELISA kit from Kainos laboratories in Japan. While initial evaluation of the data showed no changes over time during flight or bed rest, evaluation continues of FGF23 data in light of dietary factors, PTH, vitamin D status, and other biochemical and endocrine factors.

Bokhari, R.↗

Comparison of Structural and Functional Ocular Outcomes Between 14- and 70 Day Bed Rest

Purpose: To compare structural and functional ocular outcomes in healthy human subjects undergoing 14- and/or 70-day head-down-tilt bed rest (HDTBR). We hypothesized the amount of HDTBR-induced ocular changes be affected by the HDTBR duration. Methods: The studies were conducted at the NASA Flight Analogs Research Unit, The University of Texas Medical Branch at Galveston, Galveston, TX. Participants were selected using NASA standard screening procedures. Standardized NASA screening procedures and bed rest conditions (e.g., strict sleep-wake cycle, standardized diet, continuous video monitoring) were implemented in both studies. Participants maintained a 6deg HDTBR position for 14 and/or 70 consecutive days and did not engage in exercise. Weekly ophthalmological examinations were conducted in the sitting (pre/post-bed rest only) and HDT positions. Ocular outcomes of interest included: near best-corrected visual acuity (BCVA); spherical equivalent, as determined by cycloplegic autorefraction; Goldmann applanation tonometry and iCare (Icare Finland Oy, Espoo, Finland) intraocular pressure (IOP) measurement; color vision; red dot test; modified Amsler grid test; confrontational visual field; stereoscopic color fundus photography; Spectralis OCT (Heidelberg Engineering, GmbH, Heidelberg, Germany) retinal nerve fiber layer thickness (RNFLT), peripapillary and macular retinal thicknesses. Mixed-effects linear models were used to compare pre- and post-HDTBR observations between 14- and 70-day HDTBR for our continuously scaled outcomes.

Cromwell, R. L.↗

Cardiovascular and Body Fluid Adjustments During Bed Rest and Space Flight

Although a few scientific bed rest (BR) studies were conducted soon after World War II, advent of the space program provided impetus for utilizing prolonged (days-months) BR, which employed the horizontal or 6 degree head-down tilt (HDT) body positions, to simulate responses of healthy people to microgravity. Shorter (hours) HDT protocols were used to study initial mechanisms of the acclimation-deconditioning (reduction of physical fitness) syndromes. Of the major physiological factors modified during BR, reduced force on bones, ligaments, and muscles, and greatly reduced hydrostatic pressure within the cardiovascular system, the latter: which involves shifts of blood from the lower extremities into the upper body, increase in central venous pressure, and diuresis, appears to be the initial stimulus for acclimation. Increase in central venous pressure occurs in subjects during weightless parabolic flight, but not in astronauts early during orbital flight. But significant reduction in total body water (hypohydration) and plasma volume (hypovolemia) occurs in subjects during both BR and microgravity. Response of interstitial fluid volume is not as clear, It has been reported to increase during BR, and it may have increased in Skylab II and IV astronauts. Reduction of total body water, and greater proportional reduction of extracellular volume, indicates increased cellular volume which may contribute to inflight cephalic edema. Cerebral pressure abates after a few days of HDT, but not during flight. accompanied by normal (eugravity) blood constituent concentrations suggesting some degree of acclimation had occurred. But during reentry, with moderately increased +Gz (head-to-foot) acceleration and gravitational force, the microgravity "euhydration" becomes functional progressive dehydration contributing to the general reentry syndrome (GRS) which, upon landing the Shuttle, can and often results in gastrointestinal distress, disorientation, vertigo, fatigue, and fainting. Various pre-reentry hyperhydration procedures have been utilized to counteract the GRS. Thus, the somewhat decreased central venous pressure and lack of diuresis early in spaceflight suggests mechanisms other than the Gauer-Henry reflex are more important for maintaining fluid volume homeostasis in astronauts. Inflight hypohydration and hypovolemia are more important for maintaining fluid volume homeostasis in astronauts.

Greenleaf, John E.↗

Submaximal Exercise VO2 and Q During 30-Day 6 degree Head-Down Bed Rest with Isotonic and Isokinetic Exercise Training

Submaximal exercise (61+3% peak VO2) metabolism was measured before (AC day-2) and on bed rest day 4, 11, and 25 in 19 healthy men (32-42 yr) allocated into no exercise (NOE, N=5) control, and isotonic exercise (ITE, N=7)and isokinetic exercise (IKE, N=7) training groups. Training was conducting supine for two 30-min periods/d for 6 d/wk: ITE was 60-90% peak VO2: IKE was peak knee flexion-extension at 100 deg/s. Supine submaximal exercise 102 decreased significantly (*p<0.05) by 10.3%, with ITE and by 7.3%* with IKE; similar to the submaximal cardiac output (Q) change of -14.5%* (ITE) and -203%* (IKE), but different from change in peak VO2 (+1.4% with ITE and - 10.2%, with IKE) and plasma volume of -3.7% (ITE) and - 18.0% * (IKE). Thus, reduction of submaximal V02 during prolonged bed rest appears to respond to submaximal Q but is not related to change in peak VO2 or plasma volume.

Greenleaf, J. E.↗

Cardiorespiratory deconditioning with static and dynamic leg exercise during bed rest

Results are presented for an experimental study designed to compare the effects of heavy static and dynamic exercise training during 14 days of bed rest on the cardiorespiratory responses to submaximal and maximal exercise performed by seven healthy men aged 19-22 yr. The parameters measured were submaximal and maximal oxygen uptake, minute ventilation, heart rate, and plasma volume. The results indicate that exercise alone during bed rest reduces but does not eliminate the reduction in maximal oxygen uptake. An additional positive hydrostatic effect is therefore necessary to restore maximal oxygen uptake to ambulatory control levels. The greater protective effect of static exercise on maximal oxygen uptake is probably due to a greater hydrostatic component from the isometric muscular contraction. Neither the static nor the dynamic exercise training regimes are found to minimize the changes in all the variables studied, thereby suggesting a combination of static and dynamic exercises.

Stremel, R. W.↗

Effect of three day bed-rest on circulatory and hormonal responses to active orthostatic test in endurance trained athletes and untrained subjects

Circulatory and hormonal parameters were measured in endurance-trained athletes and control subjects during orthostatic tolerance tests conducted prior to and after three days of bed rest. Heart rate and blood pressure changes due to bed rest appeared to be the same in both groups. Hormonal changes, however, were different between the two groups, with the athletes having decreased sympathoadrenal activity and increased plasma renin activity. Untrained subjects had changes in cortisol secretion only.

NASA Center ARC↗

Effects of prolonged bed rest on the total peripheral resistance baroreflex

Orthostatic intolerance following prolonged exposure to microgravity continues to be a primary concern of the human space program. Reduced autonomic tone has been demonstrated to contribute to this phenomenon, and the heart rate baroreflex, in particular, has been repeatedly shown to be impaired. However, only the works of Yelle et al. have attempted to address the role of the total peripheral resistance (TPR) baroreflex, a potentially more significant contributor to blood pressure regulation. We applied a previously developed method for estimating the static gains of both the arterial and cardiopulmonary TPR baroreflexes to data obtained before and after 16-day bed rest. Reductions in the estimated static gains of the arterial (statistically significant) and cardiopulmonary TPR baroreflexes were found after bed rest. This study supports the works of Yelle et al, which imply that the TPR baroreflex is reduced after spaceflight.

Non-NASA Center↗

Twins Bed Rest Project: LBNP/Exercise Minimizes Changes in Lean Leg Mass, Strength and Endurance

Decreases in muscle strength and endurance frequently are observed in non-weightbearing conditions such as bed rest (BR), spaceflight or limb immobilization. Purpose: Ow purpose was to determine if supine treadmill exercise against simulated gravity, by application of lower body negative pressure (LBNP), prevents loss of lean leg mass, strength and endurance during 30 d of 6deg head-down bed rest (BR). Methods: Fifteen pairs of monozygous twins (8 male, 7 female pairs; 26+/-4 yrs; 170+/-12 cm; 62.6+/-11.3 kg; mean+/-SD) were subjects in the present study. One sibling of each pair of twins was randomly assigned to either an exercise (EX) or non-exercise (CON) group. The EX twin walked/jogged on a vertical treadmill within LBNP chamber 6 d/wk using a 40-min interval exercise protocol at 40-80% of pre-BR VO(sub 2peak). LBNP was adjusted individually for each subject such that footward force was between 1.0 and 1.2 times body weight (-53+/-5 mmHg LBNP). The CON twin performed no exercise during BR. Subjects performed isokinetic knee (60 and 120deg/s) and ankle (60deg/s) testing to assess strength and endurance (End) before and after BR. They also had their lean leg mass (L(sub mass)) evaluated by DEXA before and after BR. Results: Changes in peak torque (T(sub pk)) were smaller for flexion (flex) than for extension (ext) after BR and did not differ between groups. The CON group had larger decreases (P<0.05) in L(sub mass), knee and ankle ext T(sub pk), and knee ext End.

Amorim, Fabiano T.↗

Medical Monitoring during Short Radius Centrifugation in Bed-rested Subjects

The artificial gravity pilot project was designed to investigate the efficacy of daily exposure to a Gz acceleration gradient for counteracting the physiologic decrements induced by prolonged bed rest. A short radius centrifuge was used to produce a Gz gradient such that 1 g was applied at the level of the subject s heart and 2.5 g at the feet. For inclusion in the study, subjects were required to complete a 75-minute screening spin on the centrifuge. During the study, each active treatment subject was scheduled for a 60-minute spin each day for 20 consecutive days. During centrifugation, subjects were continuously monitored by a physician for signs and symptoms of pre-syncope, motion sickness, arrhythmias, joint/muscle pain and any other unanticipated problems. The physician was also present to provide emergency care in the case of a medical emergency. Cameras mounted on the centrifuge were used to provide a means of observing the subject s face and torso. Audio communication was continuously maintained. Other monitoring tools included two-lead EKG tracings, pulse oximetry, intermittent sphygmomanometer readings, lights in the peripheral visual field, and continuous blood pressure readout from a tonometry device. Thirty screening runs were attempted using twenty-seven subjects. Seven of these runs were terminated early for symptoms of pre-syncope, motion sickness, or GI distress. A total of eight subjects completed the active treatment arm of the study. Of the 160 centrifuge runs that were scheduled for these eight treatment subjects, 152 were completed, seven were terminated early, and one was not attempted. Of the seven early terminations, four were related to symptoms of pre-syncope, one to leg pain, one to GI discomfort, and one to equipment failure. Three terminations for adverse symptoms occurred on the first treatment day. Three terminations occurred on day nineteen of treatment and within 24 hours after scheduled soleus and quadriceps muscle biopsies. We have summarized the relative usefulness of the information obtained by the various monitoring modalities in making a decision to terminate a centrifuge run. The video and audio communication information was essential to the decision-making process. Heart rate and EKG tracings are considered valuable, even though no spins were terminated due to significant arrhythmias. The tonometer device was generally not reliable in this application. Our observations suggest that subjects may be less tolerant of centrifugation just after starting bed rest and after invasive procedures.

Reinertson, Randal↗

Bed Rest Muscular Atrophy

A major debilitating response from prolonged bed rest (BR) is muscle atrophy, defined as a "decrease in size of a part of tissue after full development has been attained: a wasting away of tissue as from disuse, old age, injury or disease". Part of the complicated mechanism for the dizziness, increased body instability, and exaggerated gait in patients who arise immediately after BR may be a result of not only foot pain, but also of muscular atrophy and associated reduction in lower limb strength. Also, there seems to be a close association between muscle atrophy and bone atrophy. A discussion of many facets of the total BR homeostatic syndrome has been published. The old adage that use determines form which promotes function of bone (Wolff's law) also applies to those people exposed to prolonged BR (without exercise training) in whom muscle atrophy is a consistent finding. An extreme case involved a 16-year-old boy who was ordered to bed by his mother in 1932: after 50 years in bed he had "a lily-white frame with limbs as thin as the legs of a ladder-back chair". These findings emphasize the close relationship between muscle atrophy and bone atrophy. In addition to loss of muscle mass during deconditioning, there is a significant loss of muscle strength and a decrease in protein synthesis. Because the decreases in force (strength) are proportionately greater than those in fiber size or muscle cross-sectional area, other contributory factors must be involved; muscle fiber dehydration may be important.

Greenleaf, John E.↗

Effects of 17 days of head-down bed rest on hydro-electrolytic regulation in men

Prolonged periods of head-down bed rest (HDBR) are commonly used to mimic the effects of microgravity. HDBR has been shown to produce, as in space, a cephalad redistribution of circulating blood volume with an increase in central blood volume which induces the early adaptations in blood volume regulating hormones. Changes in atrial natriuretic peptide (ANP), arginine vasopressin (AVP), renin activity and aldosterone have been observed. Many reports describe these endocrine adaptations but few investigations of rhythms are in the literature. We proposed to evaluate the circadian rhythms of the hormones and electrolytes involved in the hydro-electrolytic regulation during a HDBR study which was designed to simulate a 17-day spaceflight (Life and Microgravity Spacelab experiment, LMS, NASA).

NASA Center ARC↗

Study report on modification of the long term circulatory model for the simulation of bed rest

Modifications were made of the circulatory, fluid, and electrolyte control model which was based on the model of Guyton. The modifications included separate leg compartments and the addition of gravity dependency. It was found that these modifications allowed for more accurate bed rest simulation by simulating changes in the orthostatic gradient and simulating the response to the fluid shifts associated with bed rest.

Leonard, J. I.↗

Behavioral and Psychological Issues in Long Duration Head-down Bed Rest

Behavioral health services, similar to those offered to the U.S. astronauts who complete six-month missions on board the International Space Station, were provided to 13 long-duration head-down bed rest participants. Issues in psychological screening, selection, and support are discussed as they relate to other isolated and confined environments. Psychological services offered to participants are described, and challenges in subject selection and retention are discussed. Psychological support and training provided to both subjects and study personnel have successfully improved the well-being of study participants. Behavioral health services are indispensable to long-duration head-down tilt bed rest studies.

Seaton, Kimberly A.↗