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At least 361 records · Page 20

The anemia of primary autonomic failure and its reversal with recombinant erythropoietin

OBJECTIVE: To determine if chronic sympathetic deprivation is associated with anemia and a low erythropoietin response. DESIGN: Survey of the prevalence and characteristics of anemia in patients with severe primary autonomic failure. SETTING: A referral service for autonomic failure in a tertiary teaching hospital. PATIENTS: 84 patients with primary autonomic failure who had symptomatic orthostatic hypotension. INTERVENTION: Open-label trial with human recombinant erythropoietin. RESULTS: Anemia was present in 32 of 84 patients (38%; 95% Cl, 27% to 50%). Plasma norepinephrine levels, measured in patients standing upright, were lower in the patient group with lower hemoglobin levels. Mean values in 22 patients with a hemoglobin level of less than 120 g/L were as follows: hemoglobin, 108 g/L (range, 87 to 118 g/L); hematocrit, 0.33; corrected reticulocyte counts, 0.008; mean corpuscular volume, 89 fL (89 microns 3); serum iron, 16.5 mumol/L (92 micrograms/dL); total iron binding capacity, 43.3 mumol/L (242 micrograms/dL); ferritin, 184 micrograms/L; serum vitamin B12, 410 pmol/L (556 pg/mL); and serum folate, 22.7 nmol/L (10 ng/mL). No relation was found between serum erythropoietin and blood hemoglobin levels. In seven of nine patients with autonomic failure who had hemoglobin levels less than 120 g/L, serum erythropoietin levels decreased below the 95% confidence interval corresponding to patients with iron deficiency anemia. Therapy with recombinant erythropoietin improved mean hemoglobin levels (from 108 to 133 g/L) in all patients treated (n = 5) at relatively low doses (25 to 50 units/kg body weight, subcutaneously, three times a week). CONCLUSIONS: Our data support the hypothesis that the sympathetic nervous system stimulates erythropoiesis in humans because anemia is a frequent occurrence in patients with severe autonomic failure and is associated with a blunted erythropoietin response.

Clinical Trial↗

Cardiovascular responses to postural changes: differences with age for women and men

The cardiovascular responses to postural change, and how they are affected by aging, are inadequately described in women. Therefore, the authors examined the influence of age and sex on the responses of blood pressure, cardiac output, heart rate, and other variables to change in posture. Measurements were made after 10 minutes each in the supine, seated, and standing positions in 22 men and 25 women who ranged in age from 21 to 59 years. Several variables differed, both by sex and by age, when subjects were supine. On rising, subjects' diastolic and mean arterial pressures, heart rate, total peripheral resistance (TPR), and thoracic impedance increased; cardiac output, stroke volume, and mean stroke ejection rate decreased; and changes in all variables, except heart rate, were greater from supine to sitting than sitting to standing. The increase in heart rate was greater in the younger subjects, and increases in TPR and thoracic impedance were greater in the older subjects. Stroke volume decreased less, and TPR and thoracic impedance increased more, in the women than in the men. The increase in TPR was particularly pronounced in the older women. These studies show that the cardiovascular responses to standing differ, in some respects, between the sexes and with age. The authors suggest that the sex differences are, in part, related to greater decrease of thoracic blood volume with standing in women than in men, and that the age differences result, in part, from decreased responsiveness of the high-pressure baroreceptor system.

Posture/physiology↗

Zinc and copper balances in healthy adult males during and after 17 wk of bed rest

The effects of long-term bed rest on zinc and copper balances were measured in seven healthy men. Volunteers aged 22-54 y (mean +/- SD, 34 +/- 12 y), 168-185 cm in height (173 +/- 5 cm), and 64-86 kg in weight (74 +/- 9 kg) remained on a metabolic ward for 29 wk. Subjects were ambulatory during weeks 1-5, remained in continuous bed rest for weeks 6-22, and were reambulated during weeks 23-29. Copper and zinc were measured in weekly urine and fecal composites. Dietary intakes provided (mean +/- SD) 19.2 +/- 1.2 mumol Cu (1.22 +/- 0.08 mg), 211 +/- 11 mumol Zn (13.81 +/- 0.72 mg), 25.2 +/- 1.2 mmol Ca (1011 +/- 46 mg), 1086 +/- 46 mmol N (15.21 +/- 0.65 g), and 48.1 +/- 1.4 mmol K (1489 +/- 44 mg)/d. Bed rest increased fecal zinc excretion and decreased zinc balance, whereas copper balance was unchanged. Reambulation decreased fecal zinc excretion and increased both zinc and copper balances. These results suggest that during long-term bed rest or space flight, individuals will lose total body zinc and will retain more zinc and copper when they reambulate.

Non-NASA Center↗

Decreased catecholamine secretion from the adrenal medullae of chronically diabetic BB-Wistar rats

Many humans with IDDM eventually lose the capacity to secrete epinephrine from their adrenal medullae. The mechanism for this pathological change is unknown. We hypothesized that this abnormality is attributable to neuropathic changes in the greater splanchnic nerves or in the chromaffin cells that they innervate. To study this hypothesis, we isolated rat adrenal glands, perfused them ex vivo, and measured the epinephrine content of the perfusate under various conditions of stimulation. We used transmural electrical stimulation (20-80 V, at 10 Hz) to induce epinephrine secretion indirectly by selectively activating residual splanchnic nerve terminals within the isolated glands. Under these conditions, epinephrine secretion was severely attenuated in glands from female BB-Wistar rats with diabetes of 4 mo duration compared with their age-matched, nondiabetic controls. These perfused diabetic adrenal medullae also demonstrated decreased catecholamine release in response to direct chromaffin cell depolarization with 20 mM K+, evidence that a functional alteration exists within the chromaffin cells themselves. Nonetheless, total catecholamine content of adrenal medullae from these diabetic rats was not significantly different from controls, indicating that the secretory defect was not simply attributable to a difference in the amount of catecholamines stored and available for release. Herein, we also provide histological evidence of degenerative changes within the cholinergic nerve terminals that innervate these glands.

NASA Discipline Musculoskeletal↗

Influence of recreational activity and muscle strength on ulnar bending stiffness in men

Bone bending stiffness (modulus of elasticity [E] x moment of inertia [I]), a measure of bone strength, is related to its mineral content (BMC) and geometry and may be influenced by exercise. We evaluated the relationship of habitual recreational exercise and muscle strength to ulnar EI, width, and BMC in 51 healthy men, 28-61 yr of age. BMC and width were measured by single photon absorptiometry and EI by mechanical resistance tissue analysis. Maximum biceps strength was determined dynamically (1-RM) and grip strength isometrically. Subjects were classified as sedentary (S) (N = 13), moderately (M) (N = 18), or highly active (H) (N = 20) and exercised 0.2 +/- 0.2; 2.2 +/- 1.3; and 6.8 +/- 2.3 h.wk-1 (P < 0.001). H had greater biceps (P < 0.0005) and grip strength (P < 0.05), ulnar BMC (P < 0.05), and ulnar EI (P = 0.01) than M or S, who were similar. Amount of activity correlated with grip and biceps strength (r = 0.47 and 0.49; P < 0.001), but not with bone measurements, whereas muscle strength correlated with both EI and BMC (r = 0.40-0.52, P < 0.005). EI also correlated significantly with both BMC and ulnar width (P < 0.0001). Ulnar width and biceps strength were the only independent predictors of EI (r2 = 0.67, P < 0.0001). We conclude that levels of physical activity sufficient to increase arm strength influence ulnar bending stiffness.

NASA Discipline Musculoskeletal↗

Exercise countermeasure protocol management expert system

Exercise will be used primarily to countermeasure against deconditioning on extended space flight. In this paper we describe the development and evaluation of an expert system for exercise countermeasure protocol management. Currently, the system includes two major subsystems: baseline prescription and prescription adjustment. The baseline prescription subsystem is designed to provide initial exercise prescriptions while prescription adjustment subsystem is designed to modify the initial prescription based on the exercised progress. The system runs under three different environments: PC, SUN workstation, and Symbolic machine. The inference engine, baseline prescription module, prescription adjustment module and explanation module are developed under the Symbolic environment by using the ART (Automated Reasoning Tool) software. The Sun environment handles database management features and interfaces with PC environment to obtain physical and physiological data from exercise units on-board during the flight. Eight subjects' data have been used to evaluate the system performance by comparing the prescription of nine experienced exercise physiologists and the one prescribed by the expert system. The results of the validation test indicated that the performance of the expert system was acceptable.

NASA Discipline Data Analysis↗

Gravitoinertial force level influences arm movement control

1. The ability to move the forearm between remembered elbow joint angles immediately after rapid increases or decreases of the background gravitoinertial force (G) level was measured. The movements had been well-practiced in a normal 1G environment before the measurements in high-(1.8G) and low-force (0G) environments. The forearm and upper arm were always unsupported to maximize the influence of altered G-loading and to minimize extraneous cues about arm position. 2. Horizontal and vertical movement planes were studied to measure the effects of varying the G load in the movement plane within a given G background. Rapid and slow movements were studied to assess the role of proprioceptive feedback. 3. G level did not affect the amplitude of rapid movements, indicating that subjects were able to plan and to generate appropriate motor commands for the new G loading of the arm. The amplitude of slow movements was affected by G level, indicating that proprioceptive feedback is influenced by G level. 4. The effects of G level were similar for horizontal and vertical movements, indicating that proprioceptive information from supporting structures, such as the shoulder joint and muscles, had a role in allowing generation of the appropriate motor commands. 5. The incidence and size of dynamic overshoots were greater in 0G and for rapid movements. This G-related change in damping suggests a decrease in muscle spindle activity in 0G. A decrease in muscle spindle activity in 0G and an increase in 1.8G are consistent with the results of our prior studies on the tonic vibration reflex, locomotion, and perception of head movement trajectory in varying force backgrounds.

NASA Program Space Physiology and Countermeasures↗

Muscle fatigue in frog semitendinosus: alterations in contractile function

The purpose of this study was to characterize the contractile properties of the frog semitendinosus (ST) muscle before and during recovery from fatigue, to relate the observed functional changes to alterations in specific steps in the crossbridge model of muscle contraction, and to determine how fatigue affects the force-frequency relationship. The frog ST (22 degrees C) was fatigued by direct electrical stimulation with 100-ms 150-Hz trains at 1/s for 5 min. The fatigue protocol reduced peak twitch (Pt) and tetanic (Po) force to 32 and 8.5% of initial force, respectively. The decline in Pt was less than Po, in part due to a prolongation in the isometric contraction time (CT), which increased to 300% of the initial value. The isometric twitch duration was greatly prolonged as reflected by the lengthened CT and the 800% increase in the one-half relaxation time (1/2RT). Both Pt and Po showed a biphasic recovery, a rapid initial phase (2 min) followed by a slower (40 min) return to the prefatigue force. CT and 1/2RT also recovered in two phases, returning to 160 and 265% of control in the first 5 min. CT returned to the prefatigue value between 35 and 40 min, whereas even at 60 min 1/2RT was 133% of control. The maximal velocity of shortening, determined by the slack test, was significantly reduced [from 6.7 +/- 0.5 to 2.5 +/- 0.4 optimal muscle length/s] at fatigue. The force-frequency relationship was shifted to the left, so that optimal frequency for generating Po was reduced.(ABSTRACT TRUNCATED AT 250 WORDS).

NASA Discipline Musculoskeletal↗

Pulmonary hypoxic vasoconstriction: how strong? How fast?

We have developed a minimally invasive technique for studying regional blood flow in conscious sheep, bypassing the complications of open-chest surgery, flow probes and tracer infusion. We quantitate regional perfusion continuously on the basis of regional clearance of methane (methane is produced in the sheep rumen, enters the circulation and is eliminated nearly completely (greater than 95%) in the lung). Tracheal intubation with a dual-lumen catheter isolates the gas exchange of the right apical lobe (RAL; less than 15% of the lung) from that of the remainder of the lung, which serves as a control (CL). We measure RAL and CL methane elimination by entraining expirates in constant flows, sampled continuously for methane. Results obtained with this technique and from regional oxygen uptake are in excellent agreement. We have found that hypoxic vasoconstriction is far more potent and stable during eucapnic hypoxia than during hypocapnic hypoxia. The time course of the vasoconstriction suggests that many of the data in the literature may have been obtained prior to steady state.

NASA Discipline Regulatory Physiology↗

Spectral analysis of heart rate dynamics in elderly persons with postprandial hypotension

Prior studies suggest that postprandial hypotension in elderly persons may be due to defective sympathetic nervous system activation. We examined autonomic control of heart rate (HR) after a meal using spectral analysis of HR data in 13 old (89 +/- 6 years) and 7 young (24 +/- 4 years) subjects. Total spectral power, an index of overall HR variability, was calculated for the frequency band between 0.01 and 0.40 Hz. Relatively low-frequency power, associated with sympathetic nervous system and baroreflex activation, was calculated for the 0.01 to 0.15 Hz band. High-frequency power, representing parasympathetic influences on HR, was calculated for the 0.15 to 0.40 Hz band. Mean arterial blood pressure declined 27 +/- 8 mm Hg by 60 minutes after the meal in elderly subjects, compared with 9 +/- 8 mm Hg in young subjects (p less than or equal to 0.0001, young vs old). The mean change in low-frequency HR power from 30 to 50 minutes after the meal was +19.4 +/- 25.3 U in young subjects versus -0.1 +/- 1.5 U in old subjects (p less than or equal to 0.02). Mean change in total power was also greater in young (19.0 +/- 26.6 U) subjects compared with old subjects (0.0 +/- 1.6 U, p greater than or equal to 0.02). Mean ratio of low:high-frequency power increased 3.1 +/- 3.3 U in young subjects vs 0.5 +/- 2.7 U in old subjects (p less than or equal to 0.01). The increase in low-frequency HR power and in the low:high frequency band ratio in young subjects is consistent with sympathetic activation in the postprandial period.(ABSTRACT TRUNCATED AT 250 WORDS).

NASA Discipline Cardiopulmonary↗

Resistance to outflow of cerebrospinal fluid after central infusions of angiotensin

Infusions of artificial cerebrospinal fluid (CSF) into the cerebroventricles of conscious rats can raise CSF pressure (CSFp). This response can be modified by some neuropeptides. One of these, angiotensin, facilitates the rise in CSFp. We measured CSFp in conscious rats with a computerized system and evaluated resistance to CSF outflow during infusion of artificial CSF, with or without angiotensin, from the decay kinetics of superimposed bolus injections. Angiotensin (10 ng/min) raised CSFp (P less than 0.05) compared with solvent, but the resistance to CSF outflow of the two groups was similar (P greater than 0.05). Because CSFp was increased by angiotensin without an increase in the outflow resistance, a change in some volume compartment is likely. Angiotensin may raise CSFp by increasing CSF synthesis; this possibility is supported, since the choroid plexuses contain an intrinsic isorenin-angiotensin system. Alternatively, angiotensin may dilate pial arteries, leading to an increased intracranial blood volume.

NASA Discipline Cardiopulmonary↗

Caffeine potentiates the enhancement by choline of striatal acetylcholine release

We investigated the effect of peripherally administered caffeine (50 mg/kg), choline (30, 60, or 120 mg/kg) or combinations of both drugs on the spontaneous release of acetylcholine (ACh) from the corpus striatum of anesthetized rats using in vivo microdialysis. Caffeine alone or choline in the 30 or 60 mg/kg dose failed to increase ACh in microdialysis samples; the 120 mg/kg choline dose significantly enhanced ACh during the 80 min following drug administration. Coadministration of caffeine with choline significantly increased ACh release after each of the choline doses tested. Peak microdialysate levels with the 120 mg/kg dose were increased 112% when caffeine was additionally administered, as compared with 54% without caffeine. These results indicate that choline administration can enhance spontaneous ACh release from neurons, and that caffeine, a drug known to block adenosine receptors on these neurons, can amplify the choline effect.

Non-NASA Center↗

Space vehicle approach velocity judgments under simulated visual space conditions

There were 35 volunteers who responded when they first perceived an increase in apparent size of a collimated, two-dimensional perspective image of an Orbiter vehicle. The variables of interest included the presence (or absence) of a fixed reticle within the field of view (FOV), background starfield velocity, initial range to the vehicle and vehicle closure velocity. It was found that: 1) increasing vehicle approach velocity yielded a very small (but significant) effect of faster detection of vehicle movement, nevertheless, response variability was relatively large; 2) including the fixed reticle in the FOV produced significantly slower detection of vehicle radial movement, however this occurred only at the largest range and the magnitude of the effect was only about 15% of the one sigma value; and 3) increasing background star velocity during this judgment led to slower detection of vehicle movement. While statistically significant, this effect was small and occurred primarily at the largest range. A possible explanation for the last two findings is that other static and dynamic objects within the visual field may compete for available attention which otherwise would be available for judging image expansion; thus, the target's retinal image has to expand more than otherwise for its movement to be detected. This study also showed that the Proximity Operations Research Mockup at NASA/Ames can be used effectively to investigate a variety of visual judgment questions related to future space operations. These findings are discussed in relation to previous research and possible underlying mechanisms.

Space Flight↗

Characterizing the effects of droplines on target acquisition performance on a 3-D perspective display

The present study investigated the effects of droplines on target acquisition performance on a 3-D perspective display in which participants were required to move a cursor into a target cube as quickly as possible. Participants' performance and coordination strategies were characterized using both Fitts' law and acquisition patterns of the 3 viewer-centered target display dimensions (azimuth, elevation, and range). Participants' movement trajectories were recorded and used to determine movement times for acquisitions of the entire target and of each of its display dimensions. The goodness of fit of the data to a modified Fitts function varied widely among participants, and the presence of droplines did not have observable impacts on the goodness of fit. However, droplines helped participants navigate via straighter paths and particularly benefited range dimension acquisition. A general preference for visually overlapping the target with the cursor prior to capturing the target was found. Potential applications of this research include the design of interactive 3-D perspective displays in which fast and accurate selection and manipulation of content residing at multiple ranges may be a challenge.

Time and Motion Studies↗

The ratio of animal protein intake to potassium intake is a predictor of bone resorption in space flight analogues and in ambulatory subjects

BACKGROUND: Bone loss is a critical concern for space travelers, and a dietary countermeasure would be of great benefit. Dietary protein and potassium-associated bicarbonate precursors may have opposing effects on the acid-base balance in the body and therefore on bone loss. OBJECTIVE: In 2 studies, we examined the ability of dietary protein and potassium to predict markers of bone metabolism. DESIGN: In the first study, 8 pairs of male identical twins were assigned to 1 of 2 groups: bed rest (sedentary, or SED, group) or bed rest with supine treadmill exercise in a lower-body negative pressure chamber (EX group). In a second study, groups of 4 subjects lived in a closed chamber for 60 or 91 d, and dietary data were collected for two or three 5-d sessions. Urinary calcium, N-telopeptide, and pyridinium cross-links were measured before bed rest; on bed rest days 5-6, 12-13, 19-20, and 26-27; and daily during the chamber studies. Data were analyzed by Pearson's correlation (P < 0.05). RESULTS: The ratio of animal protein intake to potassium intake was significantly correlated with N-telopeptide in the SED group during bed rest weeks 3 and 4 (r = 0.77 and 0.80) and during the 91-d chamber study (r = 0.75). The ratio of animal protein intake to potassium intake was positively correlated with pyridinium cross-links before bed rest in the EX group (r = 0.83), in the EX group during bed rest week 1 (r = 0.84), and in the SED group during bed rest week 2 (r = 0.72) but not during either chamber study. In both studies, these relations were not significant with the ratio of vegetable protein intake to potassium intake. CONCLUSIONS: The ratio of animal protein intake to potassium intake may affect bone in ambulatory and bed-rest subjects. Changing this ratio may help to prevent bone loss on Earth and during space flight.

Clinical Trial↗

Foot-ground reaction force during resistive exercise in parabolic flight

INTRODUCTION: An interim resistance exercise device (iRED) was designed to provide resistive exercise as a countermeasure to spaceflight-induced loss of muscle strength and endurance as well as decreased bone mineral density. The purpose of this project was to compare foot-ground reaction force during iRED exercise in normal gravity (1 G) vs. microgravity (0 G) achieved during parabolic flight. METHODS: There were four subjects who performed three exercises (squat, heel raise, and deadlift) using the iRED during 1 G and 0 G at a moderate intensity (60% of maximum strength during deadlift exercise). Foot-ground reaction force was measured in the three orthogonal axes (x, y, z) using a force plate, and the magnitude of the resultant force vector was calculated (r = square root(x2 + y2 + z2)). Linear displacement (LD) was measured using a linear transducer. Peak force (Fpeak) and an index of total work (TWi) were calculated using a customized computer program. Paired t-tests were used to test if significant differences (p < or = 0.05) were observed between 1 G and 0 G exercise. RESULTS: Fpeak and TWi measured in the resultant axis were significantly less in 0 G for each of the exercises tested. During 0 G, Fpeak was 42-46% and TWi was 33-37% of that measured during 1 G. LD and average time to complete each repetition were not different from 1 G to 0 G. CONCLUSIONS: Crewmembers who perform resistive exercises during spaceflight that include the movement of a large portion of their body mass will require much greater external resistive force during 0 G than 1 G exercise to provide a sufficient stimulus to maintain muscle and bone mass.

Physical Education and Training↗

Bone Markers, Calcium Metabolism, and Calcium Kinetics During Extended-Duration Space Flight on the Mir Space Station

Bone loss is a current limitation for long-term space exploration. Bone markers, calcitropic hormones, and calcium kinetics of crew members on space missions of 4-6 months were evaluated. Spaceflight-induced bone loss was associated with increased bone resorption and decreased calcium absorption. INTRODUCTION: Bone loss is a significant concern for the health of astronauts on long-duration missions. Defining the time course and mechanism of these changes will aid in developing means to counteract these losses during space flight and will have relevance for other clinical situations that impair weight-bearing activity. MATERIALS AND METHODS: We report here results from two studies conducted during the Shuttle-Mir Science Program. Study 1 was an evaluation of bone and calcium biochemical markers of 13 subjects before and after long-duration (4-6 months) space missions. In study 2, stable calcium isotopes were used to evaluate calcium metabolism in six subjects before, during, and after flight. Relationships between measures of bone turnover, biochemical markers, and calcium kinetics were examined. RESULTS: Pre- and postflight study results confirmed that, after landing, bone resorption was increased, as indicated by increases in urinary calcium (p < 0.05) and collagen cross-links (N-telopeptide, pyridinoline, and deoxypyridinoline were all increased >55% above preflight levels, p < 0.001). Parathyroid hormone and vitamin D metabolites were unchanged at landing. Biochemical markers of bone formation were unchanged at landing, but 2-3 weeks later, both bone-specific alkaline phosphatase and osteocalcin were significantly (p < 0.01) increased above preflight levels. In studies conducted during flight, bone resorption markers were also significantly higher than before flight. The calcium kinetic data also validated that bone resorption was increased during flight compared with preflight values (668 +/- 130 versus 427 +/- 153 mg/day; p < 0.001) and clearly documented that true intestinal calcium absorption was significantly lower during flight compared with preflight values (233 +/- 87 versus 460 +/- 47 mg/day; p < 0.01). Weightlessness had a detrimental effect on the balance in bone turnover such that the daily difference in calcium retention during flight compared with preflight values approached 300 mg/day (-234 +/- 102 versus 63 +/- 75 mg/day; p < 0.01). CONCLUSIONS: These bone marker and calcium kinetic studies indicated that the bone loss that occurs during space flight is a consequence of increased bone resorption and decreased intestinal calcium absorption.

Bone and Bones/metabolism/pathology↗