A study of metabolic balance in crewmembers of Skylab IV

A metabolic balance study was conducted on the three crewmembers of the 84-day Skylab IV earth orbital mission. Dietary intake was controlled, monitored, and kept very nearly constant for a period commencing 21 days prior to flight, throughout flight, and for a period of 18 days postflight. Within the first 30 days of flight urine calcium rose to a level approx. 100% above preflight levels and remained elevated for the remainder of the flight. Fecal calcium excretion increased more slowly but continued to accelerate throughout the flight and did not return to baseline levels during the postflight period. Urinary nitrogen increased to 25-30% above preflight levels within one month following launch and thereafter gradually subsided toward control values. The overall losses of calcium averaged approx. 200 mg per day throughout the mission while nitrogen losses averaged 590 mg. Various other indices of musculoskeletal deterioration are discussed and correlated. The parallelism between the effects of weightlessness and bed rest is reviewed. It is noted, that no evidence is yet available as to the identity of the initial biological response to the absence of gravity.     

Quantitative electrocardiography during extended space flight

To assess the effects of prolonged space flight on the electrophysiological properties of the heart, vectorcardiograms (VCG) were obtained on the Skylab crews at regular intervals during flight and the pre- and postflight periods. The VCG signals were telemetered from Skylab and analyzed by digital computer. Conventional 12-lead electrocardiograms were derived from the VCG signals by a lead transformation program. Standardized exercise loads were incorporated into the experiment protocol to increase the sensitivity of the VCG for effects of deconditioning and to detect susceptibility for arrhythmias. In Skylab II, 24 preflight, 21 inflight, and 19 postflight experiments were analyzed. Statistically significant inflight changes observed in two or more crew members included: decreased resting heart rate, increased QRS duration, anterior shift QRS vector, increased QRS vector magnitude, anterior shift T vector, and increased T vector magnitude. One astronaut had occasional premature ventricular contractions (PVC) during the pre- and postflight phases. He had a single episode of multiple PVC's during heavy-load exercise testing in flight. A second astronaut had no arrhythmia during pre- or inflight testing. On postflight day 21 he had multiple PVC's and salvos of ectopic ventricular beats. He has had no recurrence of the arrhythmia. With the exception of the cardiac arrhythmias, no deleterious electrophysiological changes were observed during Skylab II.     

Blood volume regulating hormones, fluid and electrolyte modifications during 21 and 198-day space flights (Altair-MIR 1993)

During the Altair MIR' 93 mission we studied several parameters involved in blood volume regulation. The experiment was done on two cosmonauts before (B-60, B-30), during (D6, D12, D18 for French and D7, D12, D17 for Russian) and after the flight (R+1, R+3 and R+7). Space flight durations were different for two cosmonauts: for the Russian the flight duration was 198 days and for the French 21 days. On board the MIR station only urinary (volume and electrolytes, atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (cGMP) and catecholamines) and salivary (cGMP and cortisol) samples were collected, centrifuged and stored in freezer. Lithium was used as a tracer to know exactly the 24 h urine output (CNES urine collection Kit). Before and after flight, blood was drawn with an epicite needle and vacutainer system for hormonal assays (renin, antidiuretic hormone, cGMP, ANP and aldosterone) in two positions: after 30 min rest in upright seated position and after 90 min of supine position. Salivary samples were collected simultaneously. During flight a decrease of diuresis and ANP and an increase of osmolality were found. No modifications of hematocrit, but an increase of salivary cGMP and cortisol were also observed. The decrease of urinary ANP is in favor of hypovolemia as described in previous flights. The postflight examinations revealed changes in fluid-electrolyte metabolism which indicate a hypohydration status and a stimulation of hormonal system responsible for water and electrolyte retention in order to readapt to the normal gravity.     

Study of water-salt metabolism and renal function in cosmonauts

In manned space flights the renal function and water-salt metabolism undergo substantial changes. With the reserve capabilities of kidneys in mind, their function and regulation of the water-salt balance were investigated in cosmonauts postflight and in Earth-bound simulation experiments with the aid of water loading, hormonal injections (pituitrin, engiotensin, DOCA, ACTH); water- and ion-release were also studied during LBNP and physical exercises. The cosmonauts who performed space flights of 2 to 5 days showed water retention and increased urine excretion of salts during the first postflight days in response to a water load. After the 18-day flight water excretion remained unchanged whereas salt excretion increased. The capacity for osmotic concentration and urine dilution did not alter. The study of the hormonal effect in simulation experiments of different duration demonstrated a normal renal response to the hormonal excretion. After the LBNP tests and physical exercises the water- and salt-excretion declined; a correlation between the level of water- and salt-excretion and the level of these loads was established. The data on the blood- and urine-ionic composition, excretion of nitrogen metabolites, and hormones postflight as well as the results of load and functional tests suggest that changes in the renal function of cosmonauts in weightlessness are associated with regulatory effects on the kidney rather than disturbances in the function of nephron cells.     

Effects of prolonged space flight on rat skeletal muscle

The effect of a 20-day space flight on water, Na+, K+, Mg2+, Ca2+ and glycogen contents as well as on activities of glycogen metabolism enzymes--glycogen synthetase and glycogen phosphorylase--of rat skeletal muscles was studied. This data is regarded as an integral test characterizing the state of contractile tissue of the animals at the final stage of flight aboard biosatellites. The measurements indicate that there were no significant changes of cations and glycogen contents nor of the enzymic activities in fast-twitch muscles during the 20-day spaceflight. At the same time dehydration in these muscles was observed, which disappeared on the 25th postflight day. In slow-twitch antigravitational skeletal muscle (m. soleus) there was a decrease of K+ and increase of Na+ in the tissue contents. The changes disappeared at the end of the on-earth readaptation period. From the pattern of these observations, we can conclude that the 20-day space flight leads to some reversible biochemical changes of the rat skeletal muscles. A conclusion can be drawn about necessity of creating, aboard the spaceship, an artificial load on antigravitational skeletal muscles.     

Accomplishments in bioastronautics research aboard International Space Station

The tenth long-duration expedition crew is currently in residence aboard International Space Station (ISS), continuing a permanent human presence in space that began in October 2000. During that time, expedition crews have been operators and subjects for 18 Human Life Sciences investigations, to gain a better understanding of the effects of long-duration space flight on the crewmembers and of the environment in which they live. Investigations have been conducted to study: the radiation environment in the station as well as during extravehicular activity (EVA); bone demineralization and muscle deconditioning; changes in neuromuscular reflexes; muscle forces and postflight mobility; causes and possible treatment of postflight orthostatic intolerance; risk of developing kidney stones; changes in pulmonary function caused by long-duration flight as well as EVA; crew and crew–ground interactions; changes in immune function, and evaluation of imaging techniques. The experiment mix has included some conducted in flight aboard ISS as well as several which collected data only pre- and postflight. The conduct of these investigations has been facilitated by the Human Research Facility (HRF). HRF Rack 1 became the first research rack on ISS when it was installed in the US laboratory module Destiny in March 2001. The rack provides a core set of experiment hardware to support investigations, as well as power, data and commanding capability, and stowage. The second HRF rack, to complement the first with additional hardware and stowage capability, will be launched once Shuttle flights resume. Future years will see additional capability to conduct human research on ISS as International Partner modules and facility racks are added to ISS. Crew availability, both as a subject count and time, will remain a major challenge to maximizing the science return from the bioastronautics research program.     

Endocrine responses in long-duration manned space flight

The bioassay of body fluids experiment is designed to evaluate the biochemical adaptation resulting from extended exposure to space flight environment by identifying changes in hormonal and associated fluid and electrolyte parameters reflected in the blood and urine of the participating crewmen. The combined stresses of space flight include weightlessness, acceleration, confinement, restraint, long-term maintenance of high levels of performance, and possible desynchronosis. Endocrine measurements to assess the physiological cost of these stresses have been considered from two aspects. Fluid and electrolyte balance have been correlated with weight loss, changes in the excretion of aldosterone and vasopressin and fluid compartments. The second area involves the estimation of the physiological cost of maintaining a given level of performance during space flight by analysis of urinary catecholamines and cortisol. Inter-individual variability was demonstrated in most experimental indices measured; however, constant patterns have emerged which include: body weight change; increases in plasma renin activity; elevations in urinary catecholamines, ADH, aldosterone and cortisol concentrations. Plasma cortisol decreases in immediate postflight samples with subsequent increase in 24-hour urines. The measured changes are consistent with the prediction that a relative increase in thoracic blood volume upon transition to the zero-gravity environment is interpreted as a true volume expansion resulting in an osmotic diuresis. This diuresis in association with other factors ultimately results in a reduction in intravascular volume, leading to an increase in renin and a secondary aldosteronism. Once these compensatory mechanisms are effective in reestablishing positive water balance, the crewmen are considered to be essentially adapted to the null-gravity environment. Although the physiological cost of this adaptation must reflect the electrolyte deficit and perhaps other factors, it is assumed that the compensated state is adequate for the demands of the environment; however, this new homeostatic set is not believed to be without physiological cost and could, except with proper precautions, reduce the functional reserve of exposed individuals.     

Hematological and immunological changes during space flight.

This paper gives a summary of the principal hematological and immunological changes observed in crews after space flight. Reduction of red blood cell mass (2-21%) and of hemoglobin mass (12-33%) is generally observed after the US and Soviet space missions. The changes are accompanied with a loss of plasma volume (4-16%). Erythrocyte and hemoglobin concentrations in the blood remain constant, suggesting that the changes are driven by a feed-back mechanism. Immunological changes consist mainly of reduced T-lymphocyte reactivity. The results of the 96-day and 140-day Salyut-6 missions suggest that the adaptation of the immune system to spaceflight occurs in two stages: the first takes place during the first 2-3 months in space, the second follows and consists of further weakening of the immune response. Our experiments with human lymphocytes in vitro indicate that high-g enhance, whereas low-g depress lymphocyte activity. Finally, our investigations to be performed on Spacelab are described.     

Mineral and nitrogen balance study: results of metabolic observations on Skylab II 28-day orbital mission

Prediction that the various stresses of flight, particularly weightlessness, would bring about significant derangements in the metabolism of the musculoskeletal system has been based on various observations of long-term immobilized or inactive bed rest. The only attempt at controlled measurement of metabolic changes in space prior to Skylab, a study during the 14-day Gemini VII flight, revealed rather modest losses of important elements. The three astronauts of Skylab II consumed a planned day-by-day, quite constant, dietary intake of major metabolic elements in mixed foods and beverages and provided virtually complete collections of excreta for 31 days preflight, during the 28 days inflight, and for 17 days postflight. Analyses showed that, in varying degree among the crewmen, urinary calcium increased gradually during flight in a pattern similar to that observed in bed-rest studies: the mean plateau peak of urinary calcium excretion in the latter part of flight was double preflight levels. Fecal calcium excretion did not change significantly, but calcium balance, owing to the urinary calcium rise, became either negative or less positive than in preflight measurement. Increased excretion and negative balance of nitrogen and phosphorus indicated appreciable loss of muscle tissue in all three crewmen. Significant losses also occurred inflight in potassium, sodium, and magnesium. Based on the similarity in pattern and degree between these observations and those in bed rest of the losses in calcium, phosphorus, and nitrogen, musculoskeletal integrity would not be threatened in space flights of up to at least 3 months. However, if similar changes occur, indicative of continuing losses of these elements, in the planned Skylab flights for considerably more than 28 days, concern for capable musculoskeletal function should be serious for flights of very many months' duration, and greater research attention will need to be given to development of protective counter-measures.     

Erythropoietic effects of space flight

Various factors which are important in the regulation of erythropoiesis have been studied in dehydrated mice in the belief that some information would be gained relevant to the erythropoietic effects of space flight. Dehydration reduced the plasma volume and, because changes in red cell volume were minimal, the hematocrit was elevated. Thus a state of relative erythrocytosis was produced. Our understanding of the mechanism whereby these changes decreased red cell production is uncertain and appears to differ somewhat from the erythroid suppression seen following elevation of the hematocrit in animals with an absolute erythrocytosis. It is suggested that factors outside of the normal erythropoietic control pathway (such as energy balance) may play an important role in the decrease in red cell volume seen in man following space flight.     

A mathematical and experimental simulation of the hematological response to weightlessness

Two ground-based methods of weightlessness simulation--a computer model of erythropoiesis feedback regulation and bedrest--were used to investigate the mechanisms which lead to loss of red cell mass during spaceflight. Both methods were used to simulate the first Skylab mission of 28 days. Human bedrest subjects lose red cell mass linearly with time and in this study the loss was 6.7% at the end of four weeks (compared to 14% in Skylab). Postbedrest recovery of red cell mass was delayed for two weeks during which time a further decline in this quantity was noted. This is consistent with the first Skylab mission but not with the two longer flights of two and three months. Hemoconcentration, observed early in the study, was essentially maintained despite red cell loss because of continued loss of plasma volume. The computer model, using the time-varying hematocrit data to estimate red cell production rates, predicted dynamic behavior of plasma volume and red cell mass that was in close agreement with the measured values. The results support the hypothesis that red cell loss during supine bedrest is a normal physiological feedback process in response to hemoconcentration enhanced tissue oxygenation and suppression of red cell production. In contrast, the delayed postbedrest recovery of red cell mass was more difficult to explain, especially in the light of enhanced reticulocyte indices observed at the onset on ambulation. Model simulation suggested the possibilities, still to be experimentally demonstrated, that this period was marked by some combination of increased oxygen-hemoglobin affinity, small reductions in mean red cell life span, ineffective erythropoiesis, or abnormal reticulocytosis. The question of whether hemoconcentration is the sole contributor to spaceflight red cell losses also remains to be resolved.     

Medical considerations for extending human presence in space

The prospects for extending the length of time that humans can safely remain in space depend partly on resolution of a number of medical issues. Physiologic effects of weightlessness that may affect health during flight include loss of body fluid, functional alterations in the cardiovascular system, loss of red blood cells and bone mineral, compromised immune system function, and neurosensory disturbances. Some of the physiologic adaptations to weightlessness contribute to difficulties with readaptation to Earth's gravity. These include cardiovascular deconditioning and loss of body fluids and electrolytes; red blood cell mass; muscle mass, strength, and endurance; and bone mineral. Potentially harmful factors in space flight that are not related to weightlessness include radiation, altered circadian rhythms and rest/work cycles, and the closed, isolated environment of the spacecraft. There is no evidence that space flight has long-term effects on humans, except that bone mass lost during flight may not be replaced, and radiation damage is cumulative. However, the number of people who have spent several months or longer in space is still small. Only carefully-planned experiments in space preceded by thorough ground-based studies can provide the information needed to increase the amount of time humans can safely spend in space.     

The dynamics of blood biochemical parameters in cosmonauts during long-term space flights

Most of the previously obtained data on cosmonauts' metabolic state concerned certain stages of the postflight period. In this connection, all conclusions, as to metabolism peculiarities during the space flight, were to a large extent probabilistic. The purpose of this work was study of metabolism characteristics in cosmonauts directly during long-term space flights. In the capillary blood samples taken from a finger, by "Reflotron IV" biochemical analyzer, "Boehringer Mannheim" GmbH, Germany, adapted to weightlessness environments, the activity of GOT, GPT, CK, gamma-GT, total and pancreatic amylase, as well as concentration of hemoglobin, glucose, total bilirubin, uric acid, urea, creatinine, total, HDL- and LDL cholesterol, triglycerides had been determined. HDL/LDL-cholesterol ratio also was computed. The crewmembers of 6 main missions to the "Mir" orbital station, a total of 17 cosmonauts, were examined. Biochemical tests were carried out 30-60 days before launch, and in the flights different stages between the 25-th and the 423-rd days of flights. In cosmonauts during space flight had been found tendency to increase, in compare with basal level, GOT, GPT, total amylase activity, glucose and total cholesterol concentration, and tendency to decrease of CK activity, hemoglobin, HDL-cholesterol concentration, and HDL/LDL - cholesterol ratio. Some definite trends in variations of other determined biochemical parameters had not been found. The same trends of mentioned biochemical parameters alterations observed in majority of tested cosmonauts, allows to suppose existence of connection between noted metabolic alterations with influence of space flight conditions upon cosmonaut's body. Variations of other studied blood biochemical parameters depends on, probably, pure individual causes.     

Skylab experiment M-092: results of the first manned mission

Blood pressure at 30-sec intervals, heart rate, and percentage increase in leg volume continuously were recorded during a 25-min protocol in the M092 Inflight Lower Body Negative Pressure (LBNP) experiment carried out in the first manned Skylab mission. These data were collected during six tests on each crewman over a 5-month preflight period. The protocol consisted of a 5-min resting control period, 1 min at -8, 1 min at -16, 3 min at -30, 5 min at -40, and 5 min at -50 mm Hg LBNP. A 5-min recovery period followed. Inflight tests were performed at approximately 3-day intervals through the 28-day mission. Individual variations in cardiovascular responses to LBNP during the preflight period continued to be demonstrated in the inflight tests. Measurements of the calf indicated that a large volume of fluid was shifted out of the legs early in the flight and that a slower decrease in leg volume, presumably due to loss of muscle tissue, continued throughout the flight. Resting heart rates tended to be low early in the flight and to increase slightly as the flight progressed. Resting blood pressure varied but usually was characterized by slightly elevated systolic blood pressure, lower diastolic pressure, and higher pulse pressures than during preflight examinations. During LBNP inflight a much greater increase in leg volume occurred than in preflight tests. Large increases occurred even at the smallest levels of negative pressure, suggesting that the veins of the legs were relatively empty at the beginning of the LBNP. The greater volume of blood pooled in the legs was associated with greater increases of heart rate and diastolic pressure and larger falls of systolic and pulse pressure than seen in preflight tests. The LBNP protocol represented a greater stress inflight, and on three occasions it was necessary to stop the test early because of impending syncopal reactions. LBNP responses inflight appeared to predict the degree of postflight orthostatic intolerance. Postflight responses to LBNP during the first 48 hours were characterized by marked elevations of heart rate and instability of blood pressure. In addition, systolic and diastolic pressures were typically elevated considerably both at rest and also during stress. The time required for cardiovascular responses to return to preflight levels was much slower than in the case of Apollo crewmen.     

Exercise response to simulated weightlessness

Two bed rest analog studies of space flight were performed; one 14 d and the other 28 d in duration. Exercise response was studied in detail during the 28 d study and following both the 14 d and 28 d studies. This paper relates the results of these studies to physiologic changes noted during and following space flight. The most consistent change noted after both bed rest and space flight is an elevated heart rate during exercise. A second consistent finding is a postflight or postbed rest reduction in cardiac stroke volume. Cardiac output changes were variable. The inability to simulate inflight activity levels and personal exercise makes a direct comparison between bed rest and the results from specific space flights difficult.     

The endocrine system in space flight

Hormones are important effectors of the body's response to microgravity in the areas of fluid and electrolyte metabolism, erythropoiesis, and calcium metabolism. For many years antidiuretic hormone, cortisol and aldosterone have been considered the hormones most important for regulation of body fluid volume and blood levels of electrolytes, but they cannot account totally for losses of fluid and electrolytes during space flight. We have now measured atrial natriuretic factor (ANF), a hormone recently shown to regulate sodium and water excretion, in blood specimens obtained during flight. After 30 or 42 h of weightlessness, mean ANF was elevated. After 175 or 180 h, ANF had decreased by 59%, and it changed little between that time and soon after landing. There is probably an increase in ANF early inflight associated with the fluid shift, followed by a compensatory decrease in blood volume. Increased renal blood flow may cause the later ANF decrease. Erythropoietin (Ep), a hormone involved in the control of red blood cell production, was measured in blood samples taken during the first Spacelab mission and was significantly decreased on the second day of flight, suggesting also an increase in renal blood flow. Spacelab-2 investigators report that the active vitamin D metabolite 1 alpha, 25-dihydroxyvitamin D3 increased early in the flight, indicating that a stimulus for increased bone resorption occurs by 30 h after launch.     

U.S. manned space flight: the first twenty years, a biomedical status report.

In the last 20 years, the biomedical problems facing man in space have been brought into sharper focus. Space motion sickness is presently our most serious problem. Its etiology remains obscure, but the "sensory conflict" theory appears most plausible. No valid predictive tests of susceptibility exist and presently we must rely on medication for prevention or mitigation of symptoms. Adaptation/biofeedback techniques may prove useful. Cardiovascular "deconditioning" may be effectively attenuated by use of anti-g suits or plasma expanding techniques. Recent bedrest simulation studies would seem to indicate that concerns about chronically elevated central venous pressure during space flight are unfounded. The loss of red cell mass in space flight appears to be self-limited, independent of mission duration, and not of clinical concern, based on recent Soviet experiences. And finally, clodronate, a new diphosphonate effective in preventing hypercalciuria and negative calcium balance in normal human bedrested subjects, may prove effective in preventing or lessening skeletal mineral loss in space.     

Adaptation of neuromuscular activation patterns during treadmill walking after long-duration space flight

The precise neuromuscular control needed for optimal locomotion, particularly around heel strike and toe off, is known to he compromised after short duration (8- to 15-day) space flight. We hypothesized here that longer exposure to weightlessness would result in maladaptive neuromuscular activation during postflight treadmill walking. We also hypothesized that space flight would affect the ability of the sensory-motor control system to generate adaptive neuromuscular activation patterns in response to changes in visual target distance during postflight treadmill walking. Seven crewmembers, who completed 3- to 6-month missions, walked on a motorized treadmill while visually fixating on a target placed 30 cm (NEAR) or 2 m (FAR) from the subject's eyes. Electronic foot switch data and surface electromyography were collected from selected muscles of the right lower limb. Results indicate that the phasic features of neuromuscular activation were moderately affected and the relative amplitude of activity in the tibialis anterior and rectus femoris around toe off changed after space flight. Changes also were evident after space flight in how these muscles adapted to the shift in visual target distance.     

Overview of the Neurolab Spacelab mission

Neurolab is a NASA Spacelab mission with multinational cooperative participation that is dedicated to research on the nervous system. The nervous systems of all animal species have evolved in a one-g environment and are functionally influenced by the presence of gravity. The absence of gravity presents a unique opportunity to gain new insights into basic neurologic functions as well as an enhanced understanding of physiological and behavioral responses mediated by the nervous system. The primary goal of Neurolab is to expand our understanding of how the nervous system develops, functions in, and adapts to microgravity space flight. Twenty-six peer reviewed investigations using human and nonhuman test subjects were assigned to one of eight science discipline teams. Individual and integrated experiments within these teams have been designed to collect a wide range of physiological and behavior data in flight as well as pre- and postflight. Information from these investigations will be applicable to enhancing the well being and performance of future long duration space travelers, will contribute to our understanding of normal and pathological functioning of the nervous system, and may be applied by the medical community to enhance the health of humans on Earth.