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.     

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.     

System identification of dynamic closed-loop control of total peripheral resistance by arterial and cardiopulmonary baroreceptors.

Prolonged exposure to microgravity in space flight missions (days) impairs the mechanisms responsible for defense of arterial blood pressure (ABP) and cardiac output (CO) against orthostatic stress in the post-flight period. The mechanisms responsible for the observed orthostatic intolerance are not yet completely understood. Additionally, effective counter measures to attenuate this pathophysiological response are not available. The aim of this study was to investigate the ability of our proposed system identification method to predict closed-loop dynamic changes in TPR induced by changes in mean arterial pressure (MAP) and right atrial pressure (RAP). For this purpose we designed and employed a novel experimental animal model for the examination of arterial and cardiopulmonary baroreceptors in the dynamic closed-loop control of total peripheral resistance (TPR), and applied system identification to the analysis of beat-to-beat fluctuations in the measured signals. Grant numbers: NAG5-4989.     

Leg venous hemodynamics and leg volumes during a 42 day -6 degrees head-down bedrest

Seven healthy subjects were submitted to a 42-day head down bedrest, where leg venous compliance (venous distensibity index VDI) and leg volumes were assessed by mercury strain gauge plethysmography with venous occlusion and optoelectronic plethysmography, respectively. Plethysmographic and volometric measurements were made, before, during (at days 1, 4, 7, 14, 21, 26, 34 and 41), and after bedrest (days 1, 4, 7, 11 and 30 of the recovery period). Results showed a continuous decrease in leg volumes throughout bedrest, when VDI increased until day 26 of bedrest, and then decreased afterwards. The recovery period was characterized by a rapid return of VDI to prebedrest levels while leg volumes progressively normalised. These results showed that leg venous compliance changes are not always dependant upon skeletal muscle changes, and that factors other than size of muscle compartment are able to determine increases in leg venous compliance during long-term bedrest.     

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.     

Effect of fluid and salt supplementation on body hydration of athletes during prolonged hypokinesia

Body hydration decreases significantly during hypokinesia (HK) (diminished movement), but little is known about the effect of fluid and salt supplements (FSS) on body hydration during HK. The aim of this study was to measure the effect of FSS on body hydration during HK. Studies were done during 30 days pre HK period and 364 days HK period. Thirty male athletes aged 24.5 +/- 6.6 yr were chosen as subjects. They were equally divided into three groups: unsupplemented ambulatory control subjects (UACS), unsupplemented hypokinetic subjects (UHKS) and supplemented hypokinetic subjects (SHKS). Hypokinetic subjects were limited to an average walking distance of 0.7 km day-1. The SHKS group took daily 30 ml of water/kg body weight and 0.1 g of sodium chloride (NaCl)/kg body weight. Control subjects experienced no changes in their professional training and routine daily activities. Plasma volume (PV), urinary and plasma sodium (Na) and potassium (K), plasma osmolality, plasma protein, whole blood hemoglobin (Hb) and hematocrit (Hct), plasma renin activity (PRA) plasma aldosterone (PA) levels, physical characteristics, food and fluid intakes were measured. Plasma osmolality, plasma protein, urinary and plasma Na and K, whole blood Hct and Hb, PRA and PA levels decreased significantly (p < or = 0.01), while PV and body weight increased significantly (p < or = 0.01) in the SHKS group when compared with the UHKS group and did not change when compared with the UACS group. Plasma osmolality, plasma protein, urinary and plasma Na and K, PRA and PA, whole blood Hb and Hct levels increased significantly (p < or = 0.01), while PV body weight, food and fluid intakes decreased significantly (p < or = 0.01) in UHKS group when compared with the SHKS and UACS groups. The measured parameters did not change in the UACS group when compared with their baseline control values. It was shown that during HK body hydration decreased significantly, while during HK and FSS body hydration increased significantly. It was concluded that daily intake of FSS prevents the decrease of PV and blunts the increase of activity of the PRA and PA during prolonged HK.     

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.     

Chronic hyperhydration and hematological changes in trained subjects during prolonged restriction of motor activity

The objective of this investigation was to evaluate the effect of a daily intake of fluid and salt supplementation (FSS) on the hemoglobin content of endurance trained athletes during hypokinesia (decreased number of steps from 10,000 to 3000 steps per day). The studies were performed on 30 long-distance runners who had a VO2max average of 66 ml kg-1 min-1 and were in the age range of 19-24 years. Prior to their exposure to hypokinesia (HK) of 364 days, all volunteers were on an average of 10,000 steps per day. All volunteers were divided into three equal groups: the first group underwent normal ambulatory life (control subjects), the second group was kept under continuous restriction of motor activity (hypokinetic subjects), and the third group was placed under continuous restriction of motor activity and consumed 26 ml water kg-1 body weight daily and 0.1 g sodium chloride kg-1 body weight in the form of supplementation (hyperhydrated subjects). For simulation of the hypokinetic effect, the number of steps taken per day by the second and third groups of volunteers was restricted to an average of 3000. During the hypokinetic period we determined reticulocytes (Rt), hemoglobin (Hb), hematocrit (Hct), plasma volume (PV), red blood cell (RBC) mass and VO2max. In hyperhydrated volunteers the content of Hb and Hct decreased significantly, while PV, RBC mass and Rt count increased significantly. In hypokinetic volunteers Hb and Hct increased, while PV, RBC and Rt decreased significantly. It was concluded that chronic hyperhydration may be used to attentuate an increase in the Hb content of physically conditioned subjects during prolonged restriction of motor activity.     

Plasma volume and biochemical changes in athletes during bed rest chronic hyperhydration

Daily fluid and salt supplements (FSS) may be used to reduce plasma biochemical changes during bed rest (BR). The aim of this study was to evaluate the effect of a daily intake of FSS on plasma volume (PV) and biochemical changes during BR. Studies were done during a pre BR period of 15 days and during a BR period of 30 days. Thirty male athletes aged 22-26 years were chosen as subjects. They were divided into three groups: unsupplemented ambulatory control subjects (UACS), unsupplemented bed rested subjects (UBRS) and supplemented bed rested subjects (SBRS). The UBRS and SBRS were kept under a rigorous bed rest regime for 30 days. The SBRS took 26 ml water/kg body weight and 0.1 g sodium chloride/kg body weight daily. PV, protein, albumin, sodium (Na), Chloride (Cl), potassium (K), osmolality, creatinine, glucose, and whole blood haematocrit (Hct) and haemoglobin (Hb) concentrations were measured. PV increased significantly (P < or = 0.01) while plasma protein, albumin. Na, Cl, K, glucose, creatinine, osmolality, and whole blood Hb and Hct concentration decreased significantly (P < or = 0.01) in the SBRS group when compared with the UBRS group. By contrast, PV decreased significantly (P < or = 0.01), while plasma protein, albumin, Na, Cl, K, glucose, creatinine, osmolality and whole blood Hct and Hb concentration increased significantly (P < or = 0.01) in the UBRS group when compared with the SBRS and UACS groups. The measured parameters did not change significantly in the UACS group when compared with the baseline control values. It was concluded that a daily intake of FSS may be used to attenuate PV losses and biochemical changes in endurance trained athletes during bed rest.     

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.     

Preliminary application of a novel algorithm to monitor changes in pre-flight total peripheral resistance for prediction of post-flight orthostatic intolerance in astronauts

Orthostatic intolerance (OI) is a significant challenge for astronauts after long-duration spaceflight. Depending on flight duration, 20–80% of astronauts suffer from post-flight OI, which is associated with reduced vascular resistance. This paper introduces a novel algorithm for continuously monitoring changes in total peripheral resistance (TPR) by processing the peripheral arterial blood pressure (ABP). To validate, we applied our novel mathematical algorithm to the pre-flight ABP data previously recorded from twelve astronauts ten days before launch. The TPR changes were calculated by our algorithm and compared with the TPR value estimated using cardiac output/heart rate before and after phenylephrine administration. The astronauts in the post-flight presyncopal group had lower pre-flight TPR changes (1.66 times) than those in the non-presyncopal group (2.15 times). The trend in TPR changes calculated with our algorithm agreed with the TPR trend calculated using measured cardiac output in the previous study. Further data collection and algorithm refinement are needed for pre-flight detection of OI and monitoring of continuous TPR by analysis of peripheral arterial blood pressure.     

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.     

Interaction of mental and orthostatic stressors

We assessed hemodynamic responses induced by orthostatic and mental stressors, using passive head up tilt (HUT) and mental arithmetic (MA), respectively. The 15 healthy males underwent three protocols: (1) HUT alone, (2) MA in supine position and (3) MA+HUT, with sessions randomized and ≥2 weeks apart. In relation to baseline, HUT increased heart rate (HR) (+20.4±7.1 bpm; p<0.001), mean blood pressure (MBP) (+4.7±11.3 mmHg; p<0.05), diastolic blood pressure (DBP) (+6.1±11.6 mmHg; p<0.05) and total peripheral resistance (TPR) (+155±232 dyne*s/cm⁵; p<0.001) but decreased stroke volume (SV) (?33.1±13.4 ml; p<0.001) and cardiac output (CO) (?0.6±1.0 l/min; p<0.01). MA increased HR (+8.0±6.0 bpm; p<0.001), systolic blood pressure (SBP) (+9.0±7.7 mmHg; p<0.001), MBP (+10.0±6.5 mmHg; p<0.001), DBP (+9.5±7.2 mmHg; p<0.001) and CO (+0.6±0.8 l/min; p<0.01). MA+HUT increased HR (+28.8±8.4 bpm; p<0.001), SBP (+4.6±14.3 mmHg; p<0.05), MBP (+11.2±11.6 mmHg; p<0.001), DBP (+13.5±10.1 mmHg; p<0.001) and TPR (+160±199 dyne*s/cm⁵; p<0.001) but SV (?34.5±14.6 ml; p<0.001) decreased. Mental challenge during orthostatic challenge elicited greater increases in heart rate, despite similar reductions in stroke volume such as those during orthostatic stress alone. Overall, cardiac output decreases were less with combinations of mental and orthostatic challenges in comparison to orthostasis alone. This would suggest that carefully chosen mental stressors might affect orthostatic responses of people on standing up. Therefore, additional mental loading could be a useful countermeasure to alleviate the orthostatic responses of persons, particularly in those with histories of dizziness on standing up or on return to earth from the spaceflight environment of microgravity.     

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.     

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.     

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.     

Psychomotor performance during a 28 day head-down tilt with and without lower body negative pressure

Several factors may affect psychomotor performance in space: sensory-motor changes, sleep disturbances, psychological modifications induced by the social isolation and confinement. However, psychomotor performance is difficult to assess. A battery of standardized and computerized tests, so-called "Automated Portable Test System" (APTS) was devised to ascertain the cognitive, perceptive and motor abilities and their possible fluctuations according to environmental effects. Antiorthostatic bedrest, often used to simulate weightlessness, (particularly cardiovascular modifications) also constitutes a situation of social confinement and isolation. During two bedrest experiments (with head-down tilt of -6 degrees) of 28 days each, we intended to assess psychomotor performance of 6 males so as to determine whether: on the one hand, it could be altered by remaining in decubitus; on the other, the Lower Body Negative Pressure sessions, designed to prevent orthostatic intolerance back on Earth, could improve the performance. To accomplish this, part of the APTS tests as well as an automated perceptive attention test were performed. No downgrading of psychomotor performance was observed. On the contrary, the tasks were more accurately performed over time. In order to assess the experimental conditions on the acquisition phase, the learning curves were modelled. A beneficial effect of the LBNP sessions on simple tests involving the visual-motor coordination and attention faculties can only be regarded as a mere trend. Methods used in this experiment are also discussed.     

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.     

Blood volume regulating hormones response during two space related simulation protocols: four-week confinement and head-down bed-rest

The volume of regulating hormones (renin, aldosterone, arginine vasopressin and atrial natriuretic factor), electrolytes and creatinine concentrations, and blood pressure were measured in two different four-week experimental protocols: respectively -6 degrees head-down bed-rest (5 subjects) and confinement (6 subjects). We observed a significant increase (P < 0.01 at D2 vs D-5) of systolic blood pressure during confinement and a different level of response for some hormones, especially for arginine vasopressin (300% increase during confinement instead of 50% during bed-rest). The renin-angiotensin-aldosterone system was enhanced during confinement and head-down bed-rest. In both conditions, we obtained a similar pattern of response for blood volume regulating hormones. During confinement, two main factors were inactivity and stress activation of the sympathetic nervous system. In the bed-rest study the response is principally due to the fluid shift and blood volume adaptation but it is not possible to exclude the role of inactivity and stress.     

Fluid and salt supplementation effect on body hydration and electrolyte homeostasis during bed rest and ambulation

Bed rest (BR) induces significant urinary and blood electrolyte changes, but little is known about the effect of fluid and salt supplements (FSS) on catabolism, hydration and electrolytes. The aim was to measure the effect of FSS on catabolism, body hydration and electrolytes during BR.

Studies were done during 7 days of a pre-bed rest period and during 30 days of a rigorous bed rest period. Thirty male athletes aged, 24.6±7.6 years were chosen as subjects. They were divided into three groups: unsupplemented ambulatory control subjects (UACS), unsupplemented bed rested subjects (UBRS) and supplemented bed rested subjects (SBRS). The UBRS and SBRS groups were kept under a rigorous bed rest regime for 30 days. The SBRS daily took 30 ml water per kg body weight and 0.1 sodium chloride per kg body weight.

Plasma sodium (Na), potassium (K), calcium (Ca) and magnesium (Mg) levels, urinary Na, K, Ca and Mg excretion, plasma osmolality, plasma protein level, whole blood hemoglobin (Hb) and hematocrit (Hct) level increased significantly (p≤0.05), while plasma volume (PV), body weight, body fat, peak oxygen uptake, food and fluid intake decreased significantly (p≤0.05) in the UBRS group when compared with the SBRS and UACS groups. In contrast, plasma and urinary electrolytes, osmolality, protein level, whole blood Hct and Hb level decreased significantly (p≤0.05), while PV, fluid intake, body weight and peak oxygen uptake increased significantly (p≤0.05) in the SBRS group when compared with the UBRS group. The measured parameters did not change significantly in the UACS group when compared with their baseline control values.

The data indicate that FSS stabilizes electrolytes and body hydration during BR, while BR alone induces significant changes in electrolytes and body hydration. We conclude that FSS may be used to prevent catabolism and normalize body hydration status and electrolyte values during BR.