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.     

Lower body negative pressure (LBNP) as a countermeasure for long term spaceflight

The article presents the current status of lower body negative pressure (LBNP) as a countermeasure for preventing orthostatic intolerance after space flight or bed rest. Devices discussed include the Chibis vacuum suit, the Anthrorack device, a collapsible device, and an inflatable device. Two bed rest studies examined the effect of LBNP and exercise on orthostatic tolerance; plasma volume; vasopressin, plasma renin activity, and catecholamines; and side effects.     

Changes in mood status and neurotic levels during a 20-day bed rest

This study evaluated changes of mood status and depressive and neurotic levels in nine young male subjects during a 20-day 6 degrees head-down tilting bed rest and examined whether exercise training modified these changes. Participants were asked to complete psychometrical inventories on before, during, and after the bed rest experiment. Depressive and neurotic levels were enhanced during bed rest period according to the Japanese version of Zung's Self-rating Depression Scale and the Japanese version of the General Health Questionnaire. Mood state "vigor" was impaired and "confusion" was increased during bed rest and recumbent control periods compared to pre-bed rest and ambulatory control periods according to the Japanese version of Profiles of Mood State, whereas the mood "tension-anxiety", "depression-dejection", "anger-hostility" and "fatigue" were relatively stable during experiment. Isometric exercise training did not modify these results. Microgravity, along with confinement to bed and isolation from familiar environments, induced impairment of mental status.     

Usefulness of daily +2Gz load as a countermeasure against physiological problems during weightlessness.

Adaptation to head-down-tilt bed rest as a simulated microgravity leads to an abnormality of reflex control of circulation, hypovolemia and reduction of exercise capacity. We hypothesized that this cardiovascular deconditioning and reduction of exercise capacity could be prevented by a daily 1 hr centrifugation at +2Gz. To test this hypothesis, twenty healthy male subjects underwent 4 day of 6 degrees head-down-tilt bed rest. Ten of them were exposed to a +2Gz load for up to 30 min twice per day (the Gz group). The remaining 10 were not exposed to a Gz load (the no-Gz group). We estimated autonomic cardiovascular control by power spectral analysis of blood pressure and R-R interval variability, and baroreflex regulation by the transfer function analysis and the sequence method, before and after bed rest. Further, we measured hematocrit as an index of changes in plasma volume and maximal oxygen consumption as an index of exercise capacity, before and after bed rest. Result: In the no-Gz group, heart rate increased after bed rest. The high frequency power of R-R interval variability as an index of cardiac parasympathetic nervous activity, baroreflex gains estimated by transfer function analysis and the sequence method as index of the integrated arterial-cardiac baroreflex function decreased significantly. Associated with these changes, the ratio of low to high frequency power of R-R as an indicator of cardiac sympathovagal balance tended to increase after bed rest in the no-Gz group. However, those showed no significant changes after bed rest in the Gz group. Hematocrit increased after bed rest in the no-Gz group. It also tended to increase in the Gz group, however it did not achieve statistical significance. Maximal oxygen consumption decreased significantly to similar extent in both the groups. Conclusion: This result suggested that 1) a daily 1hr +2Gz load produced by a centrifuge might eliminate the changes in autonomic cardiovascular control during simulated weightlessness; 2) furthermore, it might partly reverse hypovolemia induced by bed rest; 3) however, it could not prevent the decreases in exercise capacity.     

Human thermohomeostasis onboard "Mir" and in simulated microgravity studies.

Significant changes of thermogomeostatic parameters was obtained by thermotopometric method using the techniques simulate of microgravity effects: bed rest, pressurized isolation, suit immersion (SI). However, each of ground models made rectal temperature (T) trend downward. The autothermometric study (24 and 12 sessions, 2-13th and 6-174th flight days) was carried out onboard "Mir" by two flight engineers who had preliminary tested at SI (1-2 days). Studies of German investigators onboard "Mir" confirmed: rectal T must be higher in space flight as compared to the normal environment (n=4). Comparative studies suggest that microgravity is a key factor for the human body surface T raise and abolishment of the external/internal T-gradient. T-homeostasis was not really changing during missions and could be regarded as acute effect of microgravity. After delineation of changes in body surface T--by Carnot's thermodynamic law--rectal T raise should have been anticipated. Facts pointing to the excess entropy of human body must not be passed over.     

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.     

Cardiorespiratory responses to exercise after bed rest in men and women

The purpose of this study was to compare cardiorespiratory responses of men and women to submaximal and maximal workloads before and after bed rest (BR). Fifteen male college students (19-23 yr) and 8 female nurses (23-34 yr) underwent 14 d and 17 d, respectively of bed rest. The maximal work capacity test was performed in the supine position on a bicycle ergometer just before and immediately after bed rest. The women's maximal O2 uptake (maximal VO2) was 41% lower (P<0.05) than the men's before bed rest and 42% lower (P<0.05) after bed rest. During bed rest the women's maximal VO2 decreased from 2.06 to 1.86 liter/min (-9.7%, P<0.05), and that of the men decreased from 3.52 to 3.20 liter/min (-9.1%, P<0.05). Compared with pre-BR values, after bed rest the maximal ventilatory volume was essentially unchanged in the men (+1.8%) and women (+ 2.3%), but maximal heart rate was elevated from 185 to 193 b/min (+ 4.3%, P<0.05) in the men and from 181 to 187 b/min (3.3%, P<0.05) in the women. Submaximal VO2 was unchanged after bed rest in the men but was significantly reduced in the women; the women's Hct and RBC levels were lower (P<0.05) than comparable male data. Mean corpuscular volume was unchanged in both groups pre- and post-bed rest. It is concluded that the proportional deterioration in maximal VO2 following prolonged bed rest was essentially the same in young men and women.     

Spacelab Life Sciences flight experiments: an integrated approach to the study of cardiovascular deconditioning and orthostatic hypotension

The microgravity environment of spaceflight produces rapid cardiovascular changes which are adaptive and appropriate in that setting, but are associated with significant deconditioning and orthostatic hypotension on return to Earth's gravity. The rapidity with which these space flight induced changes appear and disappear provides an ideal model for studying the underlying pathophysiological mechanisms of deconditioning and orthostatic hypotension, regardless of etiology. Since significant deconditioning is seen after flights of very short duration, muscle atrophy due to inactivity plays, at most, a small role. These changes in circulatory control associated with cephalad fluid shifts, rather than inactivity per se, are probably more important factors. In order to test this hypothesis in a systematic way, a multidisciplinary approach which defines and integrates inputs and responses from a wide variety of circulatory sub-systems is required. The cardiovascular experiments selected for Spacelab Life Sciences flights 1 and 2 provide such an approach. Both human and animal models will be utilized. Pre- and post-flight characterization of the payload crew includes determination of maximal exercise capacity (bicycle ergometry), orthostatic tolerance (lower body negative pressure), alpha and beta adrenergic sensitivity (isoproterenol and phenylephrine infusions), baroreflex sensitivity (ECG-gated, stepwise changes in carotid artery transmural pressure with a pneumatic neck collar), and responses to a 24 h period of 5 deg head-down tilt. Measurements of cardiac output (CO2 and C2H2 rebreathing), cardiac chamber dimensions (phased-array 2-dimensional echocardiography), direct central venous pressure, leg volume (Thornton sock), limb blood flow and venous compliance (occlusion plethysmography), blood and plasma volumes, renal plasma flow and glomerular filtration rates, and various hormonal levels including catecholamines and atrial natriuretic factor will also be obtained. The central venous catheter will be inserted immediately pre-launch and monitored with heart rate and blood pressure in-flight until cardiac output, respiratory gas exchange and quantitative 2D echocardiography measurements can be performed. In-flight hemodynamic measurements will be repeated at rest and during submaximal exercise daily and also during maximal exercise midway through the flight to document the timecourse and extent of cardiovascular changes in the payload crew. Parallel studies are planned for the animals. In addition to measurements of right atrial and aortic pressures and cardiac output, a dorsal micro-circulatory chamber will allow determinations of changes in capillary and venular architecture and function in six of the rats. The techniques and findings from many of the SLS-1 and 2 supporting studies have already yielded significant information about circulatory regulation in patients with both hypo- and hypertension. The flight experiments themselves will provide new data to test the validity of both animal and human models currently used for simulating the fluid shifts of a micro-gravity environment. The development of effective countermeasures, not only for short and long duration space travellers, but also for Earth-bound medical patients can then be physiologically based on experimental data rather than anecdote.     

Bone mineral measurement: Skylab experiment M-078

The observation that bone mineral is lost in patients who are either immobilized or remain in bed for extended periods of time formed the basis for the concern that large amounts of bone mineral may be lost during long periods of weightlessness. This concern was magnified when early X-ray densitometry studies suggested that rather large amounts of mineral could be lost during rather short periods of weightlessness (4-14 days). Even though these Gemini results have recently been modified, they still reflect substantial losses in the upper extremity. This led to a series of prolonged bed-rest studies (30-36 weeks) which, in addition to careful calcium balance, also employed a newer, more precise method of estimating bone mineral in the radius, ulna, and os calcis. It employed an essentially monoenergetic photon source (125I) and a scintillation detector operating in a rectilinear scanning mode to measure bone mineral by the absorptiometric technique. Bed-rest studies revealed variable mineral losses but suggested that little if any is lost during 4-6 weeks, with variable amounts being lost in 8 weeks. Losses up to 40% were noted in the os calcis after 9 months, with essentially none in the radius and ulna. When this technique was employed during the Apollo 14, 15, and 16 missions, only one crewman (CMP Apollo 15) showed significant losses in the os calcis and none in the radius or ulna. These results were, therefore, in concert with the bed-rest data but at variance with the earlier Gemini data. The variability observed during bed rest was reconciled when it was observed that the rate of loss could be correlated with the initial 24-hour urinary hydroxyproline excretion and the initial os calcis mineral content. Prediction terms were established. Measurements of the SL-II crew after 28 days of weightlessness revealed no significant bone mineral losses. The Skylab data lie within the predicted limits obtained from the bed-rest data. The relevance of the prediction terms to the Skylab and longer missions discussed.     

Cardiac and vascular adaptation to 0g with and without thigh cuffs (Antares 14 and Altair 21 day Mir spaceflights)

Cardiovascular Actaptation was evaluated on 2 astronauts: one wearing thigh cuffs from flight day 1 to 8 (14d flight), the second without cuffs (21d flight). Ultrasound investigations were performed at rest and during LBNP. Results: Without thigh cuffs the cardiovascular Actaptation consists in (1) the development of a hypovolemia with an increase of the heart rate and the cardiac output, (2) the decrease of the vascular tone in the deep (mesenteric and splanchnic) and peripheral (Lower limbs) vascular areas. The use of thigh cuffs maintains the volemia and the cardiac output at the preflight level (without heart rate increase) and prevents the loss of vascular tone in the deep and peripheral areas. Moreover the adaptative process changes since the cuffs are removed and even the volemia seems to be unaffected at this stage the vascular tone decreases to a comparable extend as during the flight without cuffs. Nevertheless during the flight without cuffs or 3 days after removing the cuffs hemodynamic signs of decreased orthostatic tolerance are present during the inflight and the 3 days post flight LBNP. Presently the possible contribution of the thigh cuffs to the reduction of the vascular deconditioning has not been tested yet.     

Autonomic function testing aboard the ISS using “PNEUMOCARD”

Investigations of blood pressure, heart rate (HR), and heart rate variability (HRV) during long term space flights on board the “ISS” have shown characteristic changes of autonomic cardiovascular control. Therefore, alterations of the autonomic nervous system occurring during spaceflight may be responsible for in- and post-flight disturbances. The device “Pneumocard” was developed to further investigate autonomic cardiovascular and respiratory function aboard the ISS. The hard-software diagnostic complex “Pneumocard” was used during in-flight experiment aboard ISS for autonomic function testing. ECG, photoplethysmography, respiration, transthoracic bioimpedance and seismocardiography were assessed in one male cosmonaut (flight lengths six month). Recordings were made prior to the flight, late during flight, and post-flight during spontaneous respiration and controlled respiration at different rates.HR remained stable during flight. The values were comparable to supine measurements on earth. Respiratory frequency and blood pressure decreased during flight. Post flight HR and BP values increased compared to in-flight data exceeding pre-flight values. Cardiac time intervals did not change dramatically during flight. Pulse wave transit time decreased during flight. The maximum of the first time derivative of the impedance cardiogram, which is highly correlated with stroke volume was not reduced in-flight.Our results demonstrate that autonomic function testing aboard the ISS using “Pneumocard” is feasible and generates data of good quality. Despite the decrease in BP, pulse wave transit time was found reduced in space as shown earlier. However, cardiac output did not decrease profoundly in the investigated cosmonaut.Autonomic testing during space flight detects individual changes in cardiovascular control and may add important information to standard medical control. The recent plans to support a flight to Mars, makes these kinds of observations all the more relevant and compelling.     

Prolonged weightlessness and calcium loss in man

Data have been accumulated from a series of studies in which men have been subjected to weightlessness in orbital space flight for periods of up to 12 weeks. These data are used to predict the long term consequences of weightlessness upon the skeletal system. Space flight induced a loss of calcium which accelerated exponentially from about 50 mg/d at the end of 1 week to approx. 300 mg/d at the end of 12 weeks. The hypercalciuria reached a constant level within 4 weeks while fecal calcium losses continued to increase throughout the period of exposure. This apparent diminution of gastrointestinal absorptive efficiency was accompanied by a slight decline in the plasma level of parathyroid hormone and a slight elevation in the plasma level of calcium and phosphorus. Although losses in mineral from the calcaneus were closely correlated with the calcium imbalance, no changes were detected in the mineral mass of the ulna and radius. From the data presented it is concluded that the process of demineralization observed in space flight is more severe than would be predicted on the basis of observations in immobilized, bed rested, or paralyzed subjects. It is, moreover, suggested that the process may not be totally reversible.     

Amino aciduria in weightlessness

Urinary excretion of amino acids by the 9 Skylab crewmen was studied as an indicator of the metabolic effects caused by exposure to the space flight environment. Intake was consistent in quality and quantity throughout the 28, 59 and 84-day flights for each of the crewmen and complete collections were accomplished. The results indicated an increased excretion in most amino acids during the first month of flight which remained elevated in the second and third months but to a lesser extent. Additional indications of change in muscle and skeletal metabolism were observed. These results point to the desirability of obtaining additional indices of alterations in protein synthetic processes in conjunction with future space flights.     

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.     

Oxygen regimen in the human peripheral tissue during space flights.

A survey of the results of the experiment "Oxygen," carried out within the scope of the INTER-KOSMOS program in members of the permanent crews and of international visiting expeditions to the Soviet orbital station Salyut-6, is given. During the 7-day space flights of the international visiting expeditions a significant decrease in pO2ic by 3.28 kPa was observed. Local oxygen utilization reduced significantly by 0.44 kPa. During hyperventilation testing after return to earth a statistically significant decrease in the peak value by 1.39 kPa was noted. In the long-term crews of the orbital station Salyut-6 the highest decrease in pO2ic of 3.8 kPa and the absolutely lowest value of 3.4 -/+ 0.5 kPa during space flight were observed. The decrease in local oxygen utilization during the flight of 0.8 kPa/min was greater than that of the visiting crews. The results indicate the importance of investigating the dynamics of the oxygen regimen for medical control of the crew members both during the space flight and during the readaptation phase after return to earth.     

Physiological effects of acute and ordinary bed rest conditions on endurance trained volunteers.

The aim of this study was to carry out a comparative study of water balance and water protein composition of the blood during exposure to acute (abrupt restriction of motor activity) and ordinary rigorous bed rest of 7 days. The studies were performed on 30 long distance runners aged 22-25 years old who had a VO2, max of 66 ml kg-1 min-1 on the average. The volunteers were divided into three equal groups: the volunteers in the 1st group were under a normal ambulatory life conditions (control subjects), the volunteers of the 2nd group subjected to an acute bed rest (abrupt restriction of motor activity) regime (acute bed rested subjects) and the volunteers of the 3rd group were submitted to ordinary and rigorous bed rest (rigorous bed rested subjects). All volunteers were on an average of 13.8 km day before taking part in this investigation. The 2nd and 3rd groups of volunteers were kept under a rigorous bed rest regime for 7 days. During the prebed rest period and actual bed rest period plasma volume (PV), total protein and protein fractions (albumins and globulins) and hematocrit were measured. Exposure to acute bed rest conditions induced a significant increase in hematocrit, hemoglobin concentration, protein fractions and marked decrease in (PV) and water balance which were significantly more pronounced than during exposure to ordinary rigorous bed rest. It was concluded that exposure to acute bed rest conditions induces significantly greater changes in water balance and water protein concentration of the blood of endurance trained volunteers than exposure to ordinary rigorous bed rest conditions.     

Countermeasure of the negative effects of weightlessness on physical systems in long-term space flights

The system of countermcasure of microgravity effects has been developed in Russia that allowed to perform safely long-term space flights. This system that includes different means and methods such as special regimens of physical exercises, axial loading (“Pingiun”) and antigravity suits, low body negative pressure device (LBNP, “Chibis”) and “cuffs” and others has been used with certain variations at certain stages of flight in 27 successfully accomplished space flights that lasted from 60 to 439 days. The pre-, in- and postflight studies performed in 57 crew members of these flights have shown that the system of countermeasure is effective in preventing or diminishing to a great extent almost all the negative effects of weightlessness in flights of a year and more duration and that the intensity and duration of changes recorded in different body systems after flights do not correlate significantly to flight durations, correlating strongly to the volume and intensity of physical exercises used during flight and especially during concluding stage of it.     

Central and regional hemodynamics in prolonged space flights.

This paper presents the results of measuring central and regional (head, forearm, calf) hemodynamics at rest and during provocative tests by the method of tetrapolar rheography in the course of Salyut-6-Soyuz and Salyut-7-Soyuz missions. The measurements were carried out during short-term (19 man-flights of 7 days in duration) and long-term (21 man-flights of 65-237 days in duration) manned missions. At rest, stroke volume (SV) and cardiac output (CO) as well as heart rate (HR) decreased insignificantly (in short-term flights) or remained essentially unchanged (in long-term flights). In prolonged flights CO increased significantly in response to exercise tests due to an increase in HR and the lack of changes in SV. After exercise tests SV and CO decreased as compared to the preflight level. During lower body negative pressure (LBNP) tests HR and CO were slightly higher than preflight. Changes in regional hemodynamics included a distinct decrease of pulse blood filling (PBF) of the calf, a reduction of the tone of large vessels of the calf and small vessels of the forearm. Head examination (in the region of the internal carotid artery) showed a decrease of PBF of the left hemisphere (during flight months 2-8) and a distinct decline of the tone of small vessels, mainly, in the right hemisphere. During LBNP tests the tone of pre- and postcapillary vessels of the brain returned to normal while PBF of the right and left hemisphere vessels declined. It has been shown that regional circulation variations depend on the area examined and are induced by a rearrangement of total hemodynamics of the human body in microgravity. This paper reviews the data concerning changes in central and regional circulation of men in space flights of different duration.