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.     

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.     

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.     

Artificial gravity: head movements during short-radius centrifugation.

Short-radius centrifugation is a potential countermeasure to long-term weightlessness. Unfortunately, head movements in a rotating environment induce serious discomfort, non-compensatory vestibulo-ocular reflexes, and subjective illusions of body tilt. In two experiments we investigated the effects of pitch and yaw head movements in participants placed supine on a rotating bed with their head at the center of rotation, feet at the rim. The vast majority of participants experienced motion sickness, inappropriate vertical nystagmus and illusory tilt and roll as predicted by a semicircular canal model. However, a small but significant number of the 28 participants experienced tilt in the predicted plane but in the opposite direction. Heart rate was elevated following one-second duration head turns. Significant adaptation occurred following a series of head turns in the light. Vertical nystagmus, motion sickness and illusory tilt all decreased with adaptation. Consequences for artificial gravity produced by short-radius centrifuges as a countermeasure are discussed. Grant numbers: NCC 9-58.     

CCISS,Vascular and BP Reg: Canadian space life science research on ISS

A comprehensive goal of the Canadian Space Agency studies (CCISS, Vascular and BP Reg) has been to investigate the efficacy of current exercise countermeasures to maintain cardiovascular and cerebrovascular health on return to Earth after up to 6-months in space. Results from the CCISS experiments revealed no significant change of in-flight heart rate during daily activities or sleep, and small, but variable between astronauts, post-flight elevation. The between astronaut differences were exaggerated during measurement of spontaneous baroreflex slope, which was reduced post-flight (P<0.05) during paced breathing with 3 astronauts having significant correlations between reduced baroreflex and reduced RR-interval (consistent with reduced fitness). Cerebrovascular autoregulation and CO₂ response were mildly impaired after flight. Some loss of in-flight fitness of astronauts in Vascular was reflected by the increase in HR at a work rate of 161±46 W of 12.3±10.5 bpm, 10.4±5.9 bpm and 13.4±5.7 bpm for early-flight, late-flight and R+1, respectively. On return to gravity, changes in resting heart rate for supine (5.9±3.5 bpm), sit (8.1±3.3 bpm) and stand (10.3±10.0 bpm) were small but variable between individuals (from −5 bpm to +20 bpm in post-flight standing) and not related to the change in exercise heart rate. In Vascular astronauts, pulse wave transit time measured to the finger tended to be reduced post-flight and carotid artery distensibility was significantly reduced (P=0.03, and n=6). The heart rate and baroreflex data suggest that some astronauts return with cardiovascular deconditioning in spite of the exercise regimes. However, greater arterial stiffness is common among all astronauts studied to date. The new CSA project, BP Reg, will monitor inflight blood pressure in an attempt to identify astronauts in greater need for countermeasures. Future research should focus on whether Vascular changes in astronauts might make them an appropriate model to study the mechanisms of arterial aging on Earth.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Effects of 12 days exposure to simulated microgravity on central circulatory hemodynamics in the rhesus monkey

Central circulatory hemodynamic responses were measured before and during the initial 9 days of a 12-day 10 degrees head-down tilt (HDT) in 4 flight-sized juvenile rhesus monkeys who were surgically instrumented with a variety of intrathoracic catheters and blood flow sensors to assess the effects of simulated microgravity on central circulatory hemodynamics. Each subject underwent measurements of aortic and left ventricular pressures, and aortic flow before and during HDT as well as during a passive head-up postural test before and after HDT. Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure were measured, and dP/dt and left ventricular elastance was calculated from hemodynamic measurements. The postural test consisted of 5 min of supine baseline control followed by 5 minutes of 90 degrees upright tilt (HUT). Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure showed no consistent alterations during HDT. Left ventricular elastance was reduced in all animals throughout HDT, indicating that cardiac compliance was increased. HDT did not consistently alter left ventricular +dP/dt, indicating no change in cardiac contractility. Heart rate during the post-HDT HUT postural test was elevated compared to pre-HDT while post-HDT cardiac output was decreased by 52% as a result of a 54% reduction in stroke volume throughout HUT. Results from this study using an instrumented rhesus monkey suggest that exposure to microgravity may increase ventricular compliance without alternating cardiac contractility. Our project supported the notion that an invasively-instrumented animal model should be viable for use in spaceflight cardiovascular experiments to assess potential changes in myocardial function and cardiac compliance.     

On laboratory simulation and the effect of small temperature oscillations about the freezing point and ice formation on the evaporation rate of water on Mars

We report measurements of the evaporation rate of water under Mars-like conditions (CO2 atmosphere at 7 mbar and approximately 0 degrees C) in which small temperature oscillations about the freezing point repeatedly formed and removed a thin layer of ice. We found that the average evaporation at 2.7 +/- 0.5 degrees C without an ice layer (corrected for the difference in gravity on Earth and on Mars) was 1.24 +/- 0.12 mm/h, while at -2.1 +/- 0.3 degrees C with an ice layer the average evaporation rate was 0.84 +/- 0.08 mm/h. These values are in good agreement with those calculated for the evaporation of liquid water and ice when it is assumed that evaporation only depends on diffusion and buoyancy. Our findings suggest that such differences in evaporation rates are entirely due to the temperature difference and that the ice layer has little effect on evaporation rate. We infer that the formation of thin layers of ice on pools of water on Mars does not significantly increase the stability of water on the surface of Mars.     

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.     

A new application of LBNP to measure orthostatic tolerance before and after 0-g simulation (water immersion)

Lower body negative pressure (LBNP) remains an important device for the generation of orthostatic stress in the space flight environment as well as a tool to measure inflight and postflight changes in orthostatic response.

These applied levels of LBNP have typically not exceeded 50–60 mm Hg negative pressure. Information is incomplete as to the levels of absolute LBNP orthostatic tolerance, and the factors responsible for their variance. A better definition of the tolerance limits for males and females could be expected to aid the evaluation of lower levels of LBNP.

An LBNP device was built to study absolute orthostatic tolerance; additionally, another LBNP device was constructed to permit orthostatic tolerance testing directly after a controlled water immersion period.

Absolute LBNP orthostatic tolerance patterns are analyzed for a group of males and females (series I). A preliminary statement on the variations of LBNP orthostatic tolerance after limited periods of water immersion and bed rest is also provided (series II).     

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.     

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.