Bright light as a chronobiological countermeasure for shiftwork in space

Work-rest schedules during long duration space missions involve several factors which could disrupt sleep and circadian temporal organisation: (1) displacement of sleep due to two-shift operations; (2) planned or unplanned schedule changes due to operational requirements; (3) social and light Zeitgebers different from those on earth; (4) changes in the gravitational exposure. Timed bright light treatment has the potential to accelerating adaptation to schedule changes. Four male subjects were exposed to two sessions of 11 d of simulated microgravity (6 ° head down tilt bedrest) with 6-h extensions of the wake period on 2 days (12-h phase delay). In a blind crossover design, subjects were exposed to bright light (> 3500 lux) for 5 h on each of the 2 shift days and the following day, at times either expected to accelerate the adjustment to the phase delay (experimental condition) or to have no phase shifting effect (control condition). Sleep was recorded polygraphically, the circadian system was monitored by recordings of heart rate and body temperature, and by collection of urine (electrolyte and hormone excretion). Only the rhythms of 6-hydroxymelatoninsulphate and potassium excretions showed significantly enhanced adjustment under the experimental condition. Different rhythms Actapted to the 12-h delay at different rates, comparable to those observed after time zone shifts. Sleep was shorter in simulated weightlessness than in normal ambulatory age-matched subjects, consistent with the shorter sleep durations characteristic of space flight. These results confirm the disruptive effects of wake-rest schedule shifts on sleep and circadian rhythms. Contrary to our initial hypothesis, 5-h exposures to bright light finishing at the time of the circadian temperature minimum were not more effective at accelerating adjustment to a 12-h schedule delay than exposures coinciding with the temperature maximum. We conclude that, while bright light may accelerate adjustment to work-rest schedule delays, any such effect seems to be largely independent from the timing of the light exposure.     

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.     

Biochemical and hemodynamic changes in normal subjects during acute and rigorous bed rest and ambulation

Rigorous bed rest (RBR) induces significant biochemical and circulatory changes. However, little is known about acute rigorous bed rest (ARBR). Measuring biochemical and circulatory variables during ARBR and RBR the aim of this study was to establish the significance of ARBR effect. Studies were done during 3 days of a pre-bed rest (BR) period and during 7 days of ARBR and RBR period. Thirty normal male individuals aged, 24.1 +/- 6.3 years were chosen as subjects. They were divided equally into three groups: 10 subjects placed under active control conditions served as unrestricted ambulatory control subjects (UACS), 10 subjects submitted to an acute rigorous bed rest served as acute rigorous bed rested subjects (ARBRS) and 10 subjects submitted to a rigorous bed rest served as rigorous bed rested subjects (RBRS). The UACS were maintained under an average running distance of 9.7 km day-1. For the ARBR effect simulation, ARBRS were submitted abruptly to BR for 7 days. They did not have any prior knowledge of the exact date and time when they would be asked to confine to RBR. For the RBR effect simulation, RBRS were subjected to BR for 7 days on a predetermined date and time known to them right away from the start of the study. Plasma renin activity (PRA), plasma cortisol (PC), plasma aldosterone (PA), plasma and urinary sodium (Na) and potassium (K) levels, heart rate (HR), cardiac output (CO), and arterial blood pressure (ABP) increased significantly, and urinary aldosterone (UA), stroke volume (SV) and plasma volume (PV) decreased significantly (p<0.05) in ARBRS and RBRS as compared with their pre-BR values and the values in UACS. Electrolyte, hormonal and hemodynamic responses were significantly (p<0.05) greater and occurred significantly faster (p<0.05) during ARBR than RBR. Parameters change insignificantly (p>0.05) in UACS compared with pre-BR control values. It was concluded that, the more abruptly muscular activity is restricted in experimental subjects while they are very active, the greater hemodynamic and biochemical change there is and probably in individuals whose muscular activity is abruptly terminated after an accident or sudden illness.     

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.     

Fluid electrolyte and hormonal changes in conditioned and unconditioned men under hypokinesia

It has been suggested that hypokinesia (diminished muscular activity) may induce more changes in fluid electrolyte metabolism and hormonal concentration of blood plasma in conditioned than unconditioned men. Thus, the objective of this investigation was to determine the effect of 7 days of hypokinesis (HK) on fluid-electrolyte excretion and hormonal content of blood in 12 physically healthy men aged 19-23 years. They were divided into two equal groups according to their physical conditioning. For the simulation of the hypokinetic effect the men were kept under a rigorous bed rest regime. During the background period (BGP), that is prior to the exposure to HK, and under HK, the rate of elimination of fluid, sodium and potassium, and the content of blood plasma aldosterone and cortisol was measured. The amount of excretion of fluid and electrolytes increased while blood plasma aldosterone content decreased. In the conditioned men, a greater excretion of fluid and electrolytes and a greater reduction of plasma aldosterone concentration was observed. It was concluded that hypokinesia induced substantial changes in fluid-electrolyte excretion and hormonal content of blood plasma in both conditioned and unconditioned men.     

Spacelab experiments on space motion sickness

Recent research results from ground and flight experiments on motion sickness and space sickness conducted by the Man Vehicle Laboratory are reviewed. New tools developed include a mathematical model for motion sickness, a method for quantitative measurements of skin pallor and blush in ambulatory subjects, and a magnitude estimation technique for ratio scaling of nausea or discomfort. These have been used to experimentally study the time course of skin pallor and subjective symptoms in laboratory motion sickness. In prolonged sickness, subjects become hypersensitive to nauseogenic stimuli. Results of a Spacelab-1 flight experiment are described in which four observers documented the stimulus factors for and the symptoms/signs of space sickness. The clinical character of space sickness differs somewhat from acute laboratory motion sickness. However SL-1 findings support the view that space sickness is fundamentally a motion sickness. Symptoms were subjectively alleviated by head movement restriction, maintenance of a familiar orientation with respect to the visual environment, and wedging between or strapping onto surfaces which provided broad contact cues confirming the absence of body motion.     

Ion regulatory function of the human kidney in prolonged space flights.

Ten cosmonauts, who performed 30-175-day space flights aboard Salyut-4 and Salyut-6, and over 60 test subjects who were exposed to bed rest of up to 182 days and immersion of up to 56 days, were examined. The renal excretion of potassium and calcium increased, reaching a maximum by the 4-6th weeks in prolonged space flights and simulation studies. During the load tests with potassium and calcium salt, excretion postflight was much higher than preflight. During potassium chloride load tests a positive correlation between the blood content of aldosterone and potassium excretion existed, whereas during calcium lactate load tests an increased calcium excretion was accompanied by a decrease in blood parathyroid hormone concentration. The most probable cause of the negative ion balance in weightlessness is the reduced capacity of tissues to retain electrolytes due to the decreased ion pool capacity. Different exercises have been shown to exert a beneficial effect on electrolyte metabolism.     

Effect of potassium and calcium loading on healthy subjects under hypokinesia and physical exercise with fluid and salt supplements

The objective of this investigation was to determine the acute responses to the electrolyte challenges under hypokinesia and physical exercise (PE) of different intensities with fluid and salt supplementation (FSS). The studies were performed on 12 physically healthy male volunteers aged 19-24 years under 364 days of hypokinesia (decreased number of steps per day) with a set of PE with FSS. The volunteers were divided into two equal groups. The first group was subjected to a set of intensive PE and the second group was submitted to a set of moderate PE. Both groups of subjects consumed daily water and salt supplements that aimed to increase the body hydration level. For simulation of the hypokinetic effect all subjects were kept under an average of 3000 steps per day. Functional tests with a potassium chloride (KCl) and calcium lactate (Cal) load were performed during the hypokinetic period of 364 days and the 60-day, prehypokinetic period that served as control, while both groups of subjects consumed daily calcium and potassium supplements. The concentration of electrolyte and hormone levels in the blood and their excretion rate in urine were determined. Renal excretion of calcium and potassium and the blood concentration thereof increased markedly in both groups of subjects. With the potassium chloride load tests the increased potassium excretion was accompanied by higher aldosterone and insulin blood levels, and with the calcium lactate load tests the increased calcium excretion was accompanied by a decreased parathyroid content in the blood. FSS and PE, regardless of intensity, failed to attenuate calcium and potassium losses. Additional intake of KCl and Cal also failed to normalize potassium and calcium abnormalities. It was concluded that during the KCl and Cal loading tests, the increased losses of potassium and calcium in the hypokinetic subjects were due to the inability of their bodies to retain these electrolytes, and that electrolyte abnormalities could not be reversed by PE or rehydration in individuals subjected to prolonged restriction of motor activity.     

Space motion sickness

Space motion sickness, presumably triggered by sudden entry into a weightless environment, occurred with unexpected frequency and severity among astronauts who flew the Skylab missions. Recovery from symptoms was complete within 3-5 days, and as revealed by the Skylab M131 Human Vestibular Function Experiment, all crewmembers were immune to experimentally induced motion sickness after mission day 8. This syndrome has been recognized as a possible threat to the early mission well-being and operational efficiency of at least some individuals who will fly space missions in the future. The causes of space motion sickness are not clearly understood, nor have satisfactory methods been identified to date for its prediction, prevention and treatment. In order to minimize the potential impact of this syndrome on Space Shuttle crew operations the National Aeronautics and Space Administration has organized a broad program of inter-disciplinary research involving a large number of scientists in the United States. Current research on the etiology of space motion sickness is based to a large extent on the so called sensory conflict theory. Investigations of the behavioral and neurophysiological consequences of intralabyrinthine, as well as intermodality sensory conflict are being performed. The work in this area is being influenced by the presumed alterations that occur in otolith behavior in weightlessness. In addition to sensory conflict, the possible relationship between observed cephalad shifts of body fluids in weightlessness and space motion sickness is being investigated. Research to date has failed to support the fluid shift theory. Research underway to identify reliable test methods for the prediction of susceptibility to space motion sickness on an individual basis includes attempts to (a) correlate susceptibility in different provocative environments; (b) correlate susceptibility with vestibular and non-vestibular response parameters, the latter including behavioral, hemodynamic and biochemical factors and (c) correlate susceptibility with rate of acquisition and length of retention of sensory adaptation. Controlled studies are also being performed during parabolic flight as a means of attempting to validate predictive tests for susceptibility to this syndrome. Research to develop new or improved countermeasures for space motion sickness is underway in two primary areas. One of these involves anti-motion sickness drugs. Significant achievements have been realized with regard to the identification of new highly efficacious drug combinations, dose levels and routes of administration. Although pronounced individual variations must be accounted for in selecting the optimum drug and dose level, combinations of promethazine plus ephedrine or scopolamine plus dexidrine are presently the drugs of choice. Work is also underway to identify side effects associated with anti-motion sickness drug use and to identify new drugs which may selectively modify activity in central neural pathways involved in motion sickness. In addition to research on drugs, efforts are being made to develop practical vestibular training methods. Variables which influence rate of acquisition of adaptation, length of retention of adaptation and transfer of protective adaptation to new environments are being evaluated. Also, included in this area is the use of biofeedback and autogenic therapy to train individuals to regulate autonomic responses associated with motion sickness. While valuable new knowledge is expected to evolve from these combined research programs, it is concluded that the final validation of predictive tests and countermeasures will require a series of controlled space flight experiments.     

Excretion of amino acids by humans during space flight

We measured the urine amino acid distribution patterns before, during and after space flight on the Space Shuttle. The urine samples were collected on two separate flights of the space shuttle. The first flight lasted 9.5 days and the second flight 15 days. Urine was collected continuously on 8 subjects for the period beginning 10 d before launch to 6 d after landing. Results: In contrast to the earlier Skylab missions where a pronounced amino aciduria was found, on shuttle the urinary amino acids showed little change with spaceflight except for a marked decrease in all of the amino acids on FD (flight day) 1 (p<0.05) and a reduction in isoleucine and valine on FD3 and FD4 (p<0.05). Conclusions: (i) Amino aciduria is not an inevitable consequence of space flight. (ii) The occurrence of amino aciduria, like muscle protein breakdown is a mission specific effect rather than part of the general human response to microgravity.     

Plasma and urine catecholamine levels in cosmonauts during long-term stay on Space Station Salyut-7.

The activity of the sympathetic adrenal system in cosmonauts exposed to a stay in space lasting for about half a year has so far been studied only by measuring catecholamine levels in plasma and urine samples taken before space flight and after landing. The device "Plasma 01", specially designed for collecting and processing venous blood from subjects during space flight on board the station Salyut-7 rendered it possible for the first time to collect and freeze samples of blood from cosmonauts in the course of a long-term 237-day space flight. A physician-cosmonaut collected samples of blood and urine from two cosmonauts over the period of days 217-219 of their stay in space. The samples were transported to Earth frozen. As indicators of the sympathetic adrenal system activity, plasma and urine concentrations of epinephrine and norepinephrine as well as urine levels of the catecholamine metabolites metanephrine, normetanephrine, and vanillylmandelic acid were determined before, during and after space flight. On days 217-219 of space flight plasma epinephrine and norepinephrine levels were slightly increased, yet not substantially different from normal. During stress situations plasma norepinephrine and epinephrine levels usually exhibit a manifold increase. On days 217-219 of space flight norepinephrine and epinephrine levels in urine were comparable with pre-flight values and the levels of their metabolites were even significantly decreased. All the parameters studied, particularly plasma norepinephrine as well as urine norepinephrine, normetanephrine, and vanillylmandelic acid, reached the highest values 8 days after landing. The results obtained suggest that, in the period of days 217-219 of the cosmonauts stay in space in the state of weightlessness, the sympathetic adrenal system is either not activated at all or there is but a slight activation induced by specific activities of the cosmonauts, whereas in the process of re-adaptation after space flight on Earth this system is considerably more markedly activated.     

Pre-adaptation to shiftwork in space

Astronauts are often required to work in shift schedules. To test pre-mission adaptation strategies and effects on the circadian system, a study was performed using microgravity simulation by head-down bedrest. Eight male subjects were studied over 4 control days, and 7 days each for pre-mission adaptation, bedrest, and readjustment. The circadian system was assessed by monitoring ECG and temperature, and by collecting urine for determination of hormones and electrolytes. Rhythms did not achieve complete adjustment within the adaptation period when the sleep-wake cycle was shortened by 1 h/day, but resynchronization continued during bedrest. After the bedrest period when the time shift was reversed by a 7-h delay within 2 days, resynchronization was achieved satisfactorily only within 7 days. From the results it is concluded that a sleep-wake cycle advance as used in this study is insufficient to keep the circadian system in pace. Under operational conditions the circadian system of astronauts may become longer and more destabilized than under controlled laboratory conditions.     

Biochemical and hormonal changes in endurance trained volunteers during and after exposure to bed rest and chronic hyperhydration.

The objective of this investigation was to assess the effect of a daily intake of fluid and salt supplementation on biochemical and hormonal changes in endurance trained volunteers aged 19-24 yrs during 30-day bed rest and during 15 days of post bed rest period. The studies were performed on 30 long distance runners aged 19-24 yrs who had a peak oxygen uptake of 66 ml/kg/min and had taken 14.5 km/day on average prior to their participation in the study. The volunteers were divided into three groups: the volunteers in the first group were under normal ambulatory conditions (control subjects); the second group subjected to bed rest alone unsupplemented (bed rested volunteers); the third group was submitted to bed rest and consumed daily 30 ml water/kg bodyweight and 0.1 g of sodium chloride (NaCl)/kg body weight (supplemented bed rested volunteers). The second and third groups of volunteers were kept under a rigorous bed rest regime for 30 days. During the pre bed rest period of 15 days, during the bed rest period of 30 days and during the post bed rest period of 15 days cyclic adenosine monophosphate, cyclic guanosine monophosphate, prostaglandins of pressor, prostaglandins depressor groups, renin activity in plasma and aldosterone in plasma and in urine were determined. We found that in bed rested volunteers without fluid and salt supplementation intake plasma renin activity and aldosterone in plasma and urine continued to increase during the bed rest period as plasma volume decreased. Moreover, in this group, cyclic nucleotides measured as an indicator of adrenosympathetic system activity increased and prostaglandins as local vasoactive substances decreased during the bed rest period. These variables returned toward the baselines in the post bed rest period as plasma volume deficit was restituted. On the other hand, the hormonal levels in the other two groups remained rather constant during the experimental period. We concluded that daily intake of fluid and salt supplementation may minimize the biochemical and hormonal changes in endurance trained volunteers dorm their exposure to bed rest conditions.     

Renal excretion of water in men under hypokinesia and physical exercise with fluid and salt supplementation

It has been suggested that under hypokinesia (reduced number of steps/day) and intensive physical exercise, the intensification of fluid excretion in men is apparently caused as a result of the inability of the body to retain optimum amounts of water. Thus, to evaluate this hypothesis, studies were performed with the use of fluid and sodium chloride (NaCl) supplements on 12 highly trained physically healthy male volunteers aged 19-24 years under 364 days of hypokinesis (HK) and a set of intensive physical exercises (PE). They were divided into two groups with 6 volunteers per group. The first group of subjects were submitted to HK and took daily fluid and salt supplements in very small doses and the second group of volunteers were subjected to intensive PE and fluid-salt supplements. For the simulation of the hypokinetic effect, both groups of subjects were kept under an average of 4000 steps/day. During the prehypokinetic period of 60 days and under the hypokinetic period of 364 days water consumed and eliminated in urine by the men, water content in blood, plasma volume, rate of glomerular filtration, renal blood flow, osmotic concentration of urine and blood were measured. Under HK, the rate of renal excretion of water increased considerably in both groups. The additional fluid and salt intake failed to normalize water balance adequately under HK and PE. It was concluded that negative water balance evidently resulted not from shortage of water in the diet but from the inability of the body to retain optimum amounts of fluid under HK and a set of intensive PEs.     

Recent advances in the physiology of whole body immersion

Recent investigations have furnished a complete analysis of the hemodynamic events accompanying whole-body immersion. About 700 ml of blood are translocated into the intrathoracic circulation, and heart volume increases by 180 +/- 62 ml. These changes are followed by an increase in stroke volume and cardiac output of over 30%. At the same time a reflex reduction of total peripheral resistance and venous tone occurs. Renin and aldosterone activity are reduced while the 17-hydroxycorticosteroid is not affected. Treatment of the subject with DOCA attenuates but does not extinguish the excess sodium excretion of immersion. This finding strengthens the arguments in favor of an unknown factor enhancing sodium excretion. Finally, the relative activation of the three factors that serve volume control, the excretory function of the kidney, capillary filtration pressure, and the thirst mechanism, is discussed.     

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.     

Hemodynamic and neurohormonal responses to extreme orthostatic stress in physically fit young adults

Blood pressure stability may be jeopardized in astronauts experiencing orthostatic stress. There is disagreement about cardiovascular and endocrine stress responses that emerge when a critical (presyncopal) state is reached. We studied hemodynamic and neurohormonal changes as induced by an orthostatic stress paradigm (head-up tilt combined with lower body negative pressure) that leads to a syncopal endpoint. From supine control to presyncope, heart rate increased by 78% and thoracic impedance by 12%. There was a 49% fall in stroke volume index, 19% in mean arterial blood pressure, 14% in total peripheral resistance index and 11% in plasma volume. Plasma norepinephrine rose by 107, epinephrine by 491, plasma renin activity by 167, and cortisol by 25%. Hemodynamic and hormonal changes of clearly different magnitude emerge in presyncope as compared to supine rest. Additional studies are warranted to reveal the exact time course of orthostatic changes up to syncopal levels.     

Fluid volumes changes induced by spaceflight

The blood volume (BV), plasma volume (PV), and extracellular fluid volume changes produced in crewmembers during spaceflights of 11-84 days were compared to changes after 14 or 28 days of bedrest. Spaceflight and bedrest produce approximately equal BV changes but the recorded PV change after spaceflight was less. However, the diurnal change in PV may explain the smaller decreases recorded after spaceflight. The cardiovascular deconditioning caused by spaceflight and bedrest was compared using the mean heart rate response to lower body negative pressure (LBNP) testing at -50 mmHg pressure. These tests show approximately equal LBNP produced heart rate changes after bedrest and spaceflight. A countermeasure which includes 4 hr of LBNP treatment at -30 mmHg and the ingestion of one l. of saline was studied and found capable of returning the heart rate response and the PV of bedrested subjects to control (prebedrest) levels suggesting that it would be useful to the crewmembers after a spaceflight.     

Immobilization induces a very rapid increase in osteoclast activity

We studied in a randomized, strictly controlled cross-over design, the effects of 6 days 6 degrees head-down tilt bed rest (HDT) in eight male healthy subjects in our metabolic ward. The study consisted of two periods (phases) of 11 days each in order to allow for the test subjects being their own controls. Both study phases were identical with respect to environmental conditions, study protocol and diet. Two days before arriving in the metabolic ward the subjects started with a diet. The diet was continued in the metabolic ward. The metabolic ward period (1l days) was divided into three parts: 4 ambulatory days, 6 days either HDT or control and 1 recovery day. Continuous urine collection started on the first day in the metabolic ward to analyze calcium excretion and bone resorption markers. On the 2nd ambulatory day in the metabolic ward and on the 5th day in HDT or control blood was drawn to analyze serum calcium, parathyroid hormone, and bone formation markers. Urinary calcium excretion was, as early as the first day in immobilization, increased (p<0.01). CTX- and NTX-excretion stayed unchanged in the first 24 h in HDT compared to the control. But already on the 2nd day of immobilization, both bone resorption markers significantly increased. We conclude from these results--pronounced rise of bone resorption markers--that already 24 h of immobilization induce a significant rise in osteoclast activity in healthy subjects. Thus, it appears possible to use short-term bed rest studies as a first step for the development of countermeasures to immobilization.     

Early cardiovascular adaptation to zero gravity simulated by head-down tilt

The early cardiovascular adaptation to zero gravity, simulated by head-down tilt at 5 degrees, was studied in a series of 10 normal young men. The validity of the model was confirmed by comparing the results with data from Apollo and Skylab flights. Tilt produced a significant central fluid shift with a transient increase in central venous pressure, later followed by an increase in left ventricular size without changes in cardiac output, arterial pressure, or contractile state. The hemodynamic changes were transient with a nearly complete return to the control state within 6 hr. The adaptation included a diuresis and a decrease in blood volume, associated with ADH, renin and aldosterone inhibition.