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.     

Cardiovascular effects of simulated zero-gravity in humans

Head-down and head-up [correction of heat-up] tilted bedrest (5 degrees) and head out water immersion (HOWI) for 6 hr were compared. Parameters: Cardiac output (rebreathing method), blood pressure (arm cuff), forearm blood flow (venous occlusion plethysmography), total peripheral (TPR), and forearm vascular (FVR) resistances, Hct, Hb, relative plasma volume (PV) changes, and plasma catecholamines (single-isotope assay). During HOWI there was as expected a decrement in TPR, FVR, Mean arterial pressure (MAP, from 100 to 80 mmHg), Hct, and PV, and--as a new finding--catecholamines, which were 30-50% lower compared with both +5 and -5 degrees bedrest. During head down tilt, MAP was elevated (to 100-110 mmHg) and catecholamines did not fall, while TPR and EVR slowly decreased over 6 hr. HOWI is a stronger stimulus than -5 degrees bedrest, probably because HOWI elevates central venous pressure more markedly emptying the peripheral veins, while bedrest permits a distension of veins, which induces an increase in sympathetic nervous activity.     

The human cardiovascular system during space flight

Purpose of the work is to analyze and to summarize the data of investigations into human hemodynamics performed over 20 years aboard orbital stations Salyut-7 and Mir with participation of 26 cosmonauts on space flights (SF) from 8 to 438 days in duration. The ultrasonic techniques and occlusive plethysmography demonstrated dynamics of changes in the cardiovascular system during SF of various durations. The parameters of general hemodynamics, the pumping function of the heart and arterial circulation in the brain remained stable in all the space flights; however, there were alterations in peripheral circulation associated with blood redistribution and hypovolemie in microgravity. The anti-gravity distribution of the vascular tone decayed gradually as unneeded. The most considerable changes were observed in leg vessels, equally in arteries (decrease in resistance) and veins (increase in maximum capacity). The lower body negative pressure test (LBNP) revealed deterioration of the gravity-dependent reactions that changed for the worse as SF duration extended. The cardiovascular deconditioning showed itself as loss of descent acceleration tolerance and orthostatic instability in the postflight period.     

Cardiovascular deconditioning during weightlessness simulation and the use of lower body negative pressure as a countermeasure to orthostatic intolerance

The cardiovascular function is one of the main disturbed by weightlessness: it is particularly affected by the astronaut's return to Earth, where symptoms linked to the cardiovascular deconditioning syndrom appear in the following forms: (1) orthostatic intolerance with its risk of syncope: (2) higher submaximal oxygen consumption for an equivalent work load. Lower Body Negative Pressure (LBNP) is intended to stimulate the venous system of the lower limbs; however, the specific effects of periodical LBNP sessions on the orthostatic intolerance have never been studied. With this objective in mind, 5 volunteers took part in two recent antiorthostatic bedrest experiments for 30 days. In the first experiment 3 subjects were submitted to several sessions of LBNP experiment per day and 2 others were controls; in the second experiment the LBNP group of the 1st one became controls and vice-versa. Two orthostatic investigations were performed: (1) 5 days before the bedrest; (2) at the end of the 30 day bedrest period. The results showed: (1) when the subjects were control, a high orthostatic intolerance post bedrest with 3 syncopes and one presyncopal state during the first minutes of the tilt test; (2) when the subjects were submitted to LBNP sessions, no orthostatic intolerance.     

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.     

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.     

Hydroelectrolytic and hormonal modifications related to prolonged bedrest in antiorthostatic position

The effects of prolonged bedrest in antiorthostatic position (-4 degrees head down) on electrolyte balance were studied in 4 young volunteers. An increase was noted in sodium excretion during the first 4 days. Plasma renin activity and plasma aldosterone varied in parallel manner during the same period. Potassium balance and creatinine clearance were not significantly modified. In light of these data we feel that prolonged bedrest in antiorthostatic position constitutes an effective way to simulate on earth metabolic and hormonal modifications occurring in man under weightlessness conditions.     

The implementation of game in a 20-day head-down tilting bed rest experiment upon mood status and neurotic levels of rest subjects

This study evaluated the effect of the implementation of game on mental health among participants in a bedrest (BR) experiment. Subjects were 12 healthy males aged 20-26, who participated in a 20-day 6-degrees head-down tilting BR experiment. The participants were asked to complete psychometrical questionnaires before, during, and after the experiment. We entrusted the participants to manage their leisure time and they intended a game in which all of them could take part over the experiment period. The general conversation and light-hearted mood among the subjects continued during the experimental period. Longitudinal data analysis showed that levels of neurosis and mood status did not deteriorate during the experiment, while our previous experiments, which were performed under the same protocol as this study except for the implementation of the game showed a distinct deterioration in psychosocial status. We consider that the implementation of game autonomously contributes to the positive effects on the mental health among the participants.     

Effectiveness of centrifuge-induced artificial gravity with ergometric exercise as a countermeasure during simulated microgravity exposure in humans

To test the effectiveness of centrifuge-induced artificial gravity with ergometric exercise, 12 healthy young men (20.7 +/- 1.9 yr) were exposed to simulated microgravity for 14 days of -6 degrees head-down bedrest. Half the subjects were randomly selected and loaded 1.2 G artificial gravity with 60 W (four out of six subjects) or 40 W (two out of six subjects) of ergometric workload on days 1, 2, 3, 5, 7, 9, 11, 12, 13, 14 (CM group). The rest of the subjects served as the control. Anti-G score, defined as the G-load x running time to the endpoint, was significantly elongated by the load of the centrifuge-ergometer. Plasma volume loss was suppressed (-5.0 +/- 2.4 vs. -16.4 +/- 1.9%), and fluid volume shift was prevented by the countermeasure load. Elevated heart rate and muscle sympathetic nerve activity after bedrest were counteracted, and exaggerated response to head-up tilt was also suppressed. Centrifuge-induced artificial gravity with exercise is effective in preventing cardiovascular deconditioning due to microgravity exposure, however, an effective and appropriate regimen (magnitude of G-load and exercise workload) should be determined in future studies.     

Evaluation of spontaneous baroreflex response after 28 days head down tilt bedrest

The spontaneous baroreflex response was evaluated during supine rest and head up tilt (60 degrees) before and immediately after a 28 day 6 degrees HDT bedrest in 6 healthy adult men (age 30-42 years). Sequences of 3 or more beats where RR-interval and systolic blood pressure changed in the same direction were used to evaluate baroreflex response slope (BRS). Prior to bedrest, the mean BRS and RR-interval were 18.0 +/- 3.9 ms/mm Hg and 926 +/- 61 ms at rest and 10.5 +/- 2.5 ms/mm Hg and 772 +/- 63 ms during the first 10 min of 60 degrees tilt. Following bedrest, these values changed to 15.6 +/- 2.7 ms/mm Hg and 780 +/- 53 ms at rest, and to 6.5 +/- 1.2 ms/mm Hg and 636 +/- 44 ms during tilt. Thus, (1) the spontaneous baroreflex can be evaluated in human subjects during experiments of orthostatic stress; (2) the baroreflex slope was reduced on going from supine to the head up tilt position; and (3) 28 days of bedrest reduced the spontaneous baroreflex slope.     

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.     

Changes in the loco-regional Cerebral Blood Flow (r.C.B.F.) during a simulation of weightlessness.

Experiments of prolonged bedrest in antiorthostatic position are conducted in order to simulated cardio-circulatory modifications observed in weightlessness. Until now, no studies of r.C.B.F. have been effected in these conditions. Six young, healthy volunteers (average age 23.8) were placed in strict bedrest and in antiorthostatic position -4 degrees for 7 days. The r.C.B.F. measurements were studied by 133Xe inhalation method using a 32 detectors system. Studies were made first in basal conditions, then between the 6th and 12th hr, and finally between the 72nd and the 78th hr after the beginning of the experiment. Three of the subjects received 0.450 mg of Clonidine daily during the experiment. In the subjects having taken no Clonidine, we observed a constant increase in r.C.B.F. (12, 17 and 16% respectively) in the first 12 hr; at the 72nd hour, all values had returned to basal state. This findings agrees with the well known notion of a rapid correction of hemodynamic disturbances observed in the first days of weightlessness. In the subjects treated with Clonidine, the increase of r.C.B.F. did not occur. Several mechanisms of action are possible; the Clonidine affecting either the heart by inhibiting volemic atrial receptors or the brain by direct vasoconstriction.     

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.     

Status of vestibular function after prolonged bedrest.

6 young, healthy, male volunteers were submitted to one week of head down (-4 degrees) bedrest. This position simulates the cerebral hemodynamic conditions in weightlessness. Measurements of vestibular equilibrium and of oculomotor system function were made before and after the prolonged bedrest. Analysis of the results indicates that vestibular responses, as measured by the maximal speed of the slow phase of the provoked nystagmus (caloric and sinusoidal rotatory stimulations), are decreased after prolonged bedrest. This statistically significant diminution requires confirmation with a greater number of cases. The reflex conflicting or interacting with the cervico-ocular and optokinetic reflexes on the one hand and the foveal vision on the other, is one of several possible explanations for the observed changes.     

Cardiovascular reflexes during rest and exercise modified by gravitational stresses.

The hypotheses tested were whether variations in central venous pressure via the low pressure baroreceptors would take over or modify the arterial baroreceptor function, and further to which extent local and "whole body" hydrostatic stresses influence blood flow distribution. We investigated total forearm and skin blood flow (venous occlusion plethysmography and 133-Xe clearance) and cardiac output (rebreathing method) among other parameters. Hypo- and hyper-gravitational stresses were simulated by LBNP, LBPP, water immersion and lowering of the arm. The changes in flow distribution in the arm were ascribed to arterial baroreceptor function and not to low pressure baroreceptor activity. The enhancement of venous return during water immersion increased exercise tolerance during heat stress presumably due both to increased stroke volume and decreased venous pooling. The response to sustained handgrip exercise during LBNP and LBPP was not different from control measurements and the effects explained by arterial baroreceptor function. Application of exercise and local hydrostatic stresses in combination with gravitational stresses represent an interesting model for further study of the mechanisms behind the distribution of cardiac output to the peripheral organs.     

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.     

Effects of repeated long duration +2Gz load on man's cardiovascular function

Usefulness of a short-arm human centrifuge is expected when it is used in space as a countermeasure against cardiovascular deconditioning, problem of bone-calcium metabolism, etc. However, nothing is solidly established regarding the most desirable program for artificial G application. Accordingly, this study was designed to analytically evaluate the effects of repeated long duration +Gz load on human cardiovascular function. Recently heart rate spectral analysis has been recognized as a powerful tool for quantitatively evaluating parasympathetic and sympathetic activity separately in human. It is reported that power of the high frequency component (HF-p) is mediated selectively by parasympathetic activity and the power ratio of low to high frequency components(LF/HF) is indicative of cardiac sympathetic activity or cardiac sympathovagal balance. Sequence method is developed to examine spontaneous baroreceptor reflex sensitivity (BRS). We studied cardiovascular control function by using these methods in 9 healthy men before and after 7 days of daily repeated 1hour +2Gz load. When compared with the data of pre-G load period, post-G load period, decrease of HR, increases of HF-p and BRS were statistically significant. SBP, DBP and LF/HF tended to decrease, however, these changes were not statistically significant. This results indicate that repeated +2Gz load increases parasympathetic activity and arterial baroreceptor-cardiac reflex sensitivity. In recent years, many investigators suggest that space flight and head-down bedrest leads to impaired baroreceptor-cardiac reflex responses and decrease of parasympathetic activity, which may contribute to orthostatic intolerance. So our results suggest that daily repeated 1hour +2Gz load would be useful in preventing post-flight orthostatic intolerance.     

Correlation of macro and micro cardiovascular function during weightlessness and simulated weightlessness

The investigation of cardiovascular function necessarily involves a consideration of the exchange of substances at the capillary. If cardiovascular function is compromised or in any way altered during exposure to zero gravity in space, then it stands to reason that microvascular function is also modified. We have shown that an increase in cardiac output similar to that reported during simulated weightlessness is associated with a doubling of the number of post-capillary venules and a reduction in the number of arterioles by 35%. If the weightlessness of space travel produces similar changes in cardiopulmonary volume and cardiac output, a reasonable expectation is that astronauts will undergo venous neovascularization. We have developed an animal model in which to correlate microvascular and systemic cardiovascular function. The microcirculatory preparation consists of a lightweight, thermo-neutral chamber implanted around intact skeletal muscle on the back of a rat. Using this technique, the performed microvasculature of the cutaneous maximus muscle may be observed in the conscious, unanesthetized animal. Microcirculatory variables which may be obtained include venular and arteriolar numbers, lengths and diameters, single vessel flow velocities, vasomotion, capillary hematocrit anastomoses and orders of branching. Systemic hemodynamic monitoring of cardiac output by electromagnetic flowmetry, and arterial and venous pressures allows correlation of macro- and microcirculatory changes at the same time, in the same animal. Observed and calculated hemodynamic variables also include pulse pressure, heart rate, stroke volume, total peripheral resistance, aortic compliance, minute work, peak aortic flow velocity and systolic time interval. In this manner, an integrated assessment of total cardiovascular function may be obtained in the same animal without the complicating influence of anesthetics.     

Metabolic changes in the animals subjected to space flight

The activity of the enzymes involved in aminoacid metabolism (tyrosine aminotransferase, TAT, tryptophan pyrrolase TP, serine dehydratase, SD) with rapid response to glucocorticoids and enzymes requiring for activity increase repeated administration of corticosterone (alanine aminotransferase, ALT, aspartate aminotransferase, AST) in liver, the changes of lipolysis in adipose tissue and the plasma corticosterone levels were studied in rats subjected to space flight (F), in animals from synchron model experiments (SM, simulated conditions of space flight in laboratory) and in intact controls (C). The increase of plasma corticosterone concentration and of the activity of rapidly (TAT, TP, SD) and slowly activating enzymes (ALT, AST) was found in F group 6-10 hr after space flight (18.5 days on biosatellite COSMOS 1129). This suggested the presence of acute-stress (associated primarily with the landing) and chronic stress induced hypercorticosteronemia during the flight. After the short 6-day period of recovery the plasma corticosterone concentrations and the activities of liver enzymes returned to control levels. The exposition of animals to repeated immobilization stress showed higher response of corticosterone levels in flight rats as compared to intact controls. No changes in basal lipolysis were observed in flight rats in comparison to intact controls, however the stimulation of lipolysis by norepinephrine was lower in animals from F and SM groups. This lower response of lipolytic processes to norepinephrine was found in flight animals also after six days period of recovery. These results showed that there are important changes in the regulation of lipolytic processes in adipose tissue of rats after space flight and in the conditions of model 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.