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Contractile characteristics of the triceps surae muscle in healthy males during 120-days head-down tilt (HDT) and countermeasures.

To reveal mechanisms responsible for changes in muscle contractility during microgravity, it seems expedient to perform similar studies under microgravity or conditions simulating microgravity. Among standard methods for simulating microgravity, hypokinesia modelling support unloading (or rather its redistribution), and hypodynamia are employed. Absence of weight loading, decreased muscular effort characteristic of the Earth conditions due to counteracting gravity, results in a general muscle underloading and therefore in lowered activity of the proprioceptive input. This may be one of the reasons not only for a resetting of motor coordination and control, but also for a gradual development of a persistent change in the motor control system. The basis of countermeasures against negative consequences of microgravity (hypokinesia) is the correct choice of countermeasures. In this connection of specific interest is a study of the magnitude of change in skeletal muscle contractility in humans after a variety of countermeasures when functional activity is lowered by a long-term 120-days HDT which is an adequate simulation of physiological microgravity-induced effects.

Adult↗

[The problem of creation of artificial gravity with the use of a short-radius centrifuge for medical support of interplanetary piloted missions].

On the evidence of orbital flights, the system of countermeasures against the effects of microgravity does not fully make for deconditioning of a number of human organs and systems and recovery of preflight physical status and working ability of members of long-term missions takes 1.5 to 2 mos. of the post-flight rehabilitation. In order to maintain the physical form, health and performance of crews in future interplanetary missions, we should be ready to offer them a novel countermeasure, i.e. regular sessions of artificial gravity generated by a short-radius centrifuge (SRC) on board vehicles. The articles presents the substantiation and concept of ground-based simulation studies of health benefits from SRC in interplanetary missions. Of primary concern is development of SRC regimens that will put up a strong opposition to microgravity, assure crew safety, and reduce to the minimum time to fulfill the in-flight countermeasure program. Answers to arising questions can be found by consolidation of the expertise and resources of the countries willing to meet this challenge.

Adaptation, Physiological↗

Reduced spontaneous baroreflex response slope during lower body negative pressure after 28 days of head-down bed rest.

Effects of 28 days of continuous 6 degrees head-down tilt bed rest on spontaneous vagally mediated baroreflex response slope were evaluated from beat-by-beat relationships between R-R interval and systolic arterial blood pressure. Twelve healthy men (age 27-42 yr) were assigned to either countermeasure (CM) or no-countermeasure (no-CM) groups. CM consisted of strenuous short-term exercise once per day 6 days/wk from days 7 to 28 and lower body negative pressure (LBNP) for 15 min on days 16, 18, 20, and 22-28. Spontaneous baroreflex slope was evaluated by application of linear regression to sequences of at least three beats in which systolic blood pressure and R-R interval changed in the same direction. Measurements were made pre-, mid- (day 15), and post-bed rest at rest and during progressive LBNP tests (3 min at each of -20, -30, -40, and -50 mmHg). R-R interval decreased progressively and significantly (P < 0.0001) over duration of bed rest. Spontaneous baroreflex slope at rest in pre-bed rest was 18.5 +/- 2.1 ms/mm Hg for CM and 14.9 +/- 1.6 ms/mmHg for no-CM. There was a significant reduction in baroreflex slope as a function of bed rest, and it was further reduced during LBNP (P < 0.0001). Between CM and no-CM groups differences existed, but these were present pre-bed rest and appeared unaffected by countermeasures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A review of muscle atrophy in microgravity and during prolonged bed rest.

With the prospect of long duration space missions in Earth orbit or to Mars, there is a need for adequate information on the physiological adaptations that will occur. One consequence of prolonged exposure to microgravity is muscle atrophy (loss of muscle mass). After a long duration space flight, muscle atrophy along with skeletal calcium loss would affect the capacity of astronauts to re-adapt to gravity on return to Earth. Of importance are any countermeasures which can attenuate the adaptive responses to microgravity. Experimentation is difficult in space with small subject numbers and mission constraints. Prolonged bed rest using healthy volunteers is used as an Earth-based model to simulate the muscle atrophy which occurs in the microgravity environment.

Adaptation, Physiological↗

[Changes of blood circulation, muscle and skeletal systems in 30 d tail-suspended [correction of tail-suspented] rats].

OBJECTIVE: To confirm the tail-suspended rat model for the study of countermeasures against weightlessness. METHOD: The changes of blood circulation, muscle and skeletal systems in control group rats (n = 15) and 30 d tail-suspended rats (n = 15) were compared. RESULT: Compared with the control group, the hemorrheology and erythrocyte deformability decreased significantly, muscle-fiber atrophy, muscle contraction function decreased, the type I muscle fibers transformed to the type II muscle fibers, bone-mineral content of L3 and load capacity of femur declined, bone metabolism changed in the suspended rats. CONCLUSION: The tail-suspended rat is a suitable animal model for the study of countermeasures against weightlessness.

Animals↗

Advantages and disadvantages of fludrocortisone or saline load in preventing post-spaceflight orthostatic hypotension.

The purpose of this study was to compare the effectiveness of saline load to fludrocortisone (florinef) as countermeasures for reduced plasma volume and orthostatic intolerance after spaceflight. Eleven males (ages 30-50 yr) underwent a 3-day ambulatory baseline period followed by 7 days of 6 degrees head-down bedrest, during which cardiopulmonary and arterial baroreflex sensitivity and plasma volume (PV) were determined. During pre-bedrest and 2.5 h after treatment on day 8, PV was also measured and subjects underwent a 15-min unsupported stand test. Treatments consisted of 8 salt tablets (1 g NaCl per tablet) and 960 ml of water in 5 subjects and 0.6 mg (0.2 mg x 3) over 24 h in the other 6 subjects. PV decreased by 12% on day 7 of bedrest. This was restored on day 8 by florinef but not by saline load. The effect of florinef on PV was paralleled by decreases in urine volume and the urinary sodium/potassium ratio. Reduced PV was associated with greater vascular resistance for the same drop in central venous pressure, suggesting less vasoconstriction reserve after bedrest. Carotid baroreflex control of heart rate was attenuated after 7 days of bedrest. Both baroreflex functions were restored by florinef but not saline load. Only 1 of 6 subjects showed syncopal symptoms in the florinef-treated group, whereas 4 of 5 subjects did so in the saline-load group. Acute florinef treatment appears to have distinct advantages as a protective measure for post-bedrest orthostatic intolerance, not only through its salt retaining, volume-expanding mineralcorticoid effect, but possibly through its actions on baroreflex and sympathetic functions.

Administration, Oral↗

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.

Bed Rest↗

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.

Adult↗

[Prophylaxis of the unfavorable shifts in mineral turnover in bones during extended exposure to the conditions reproducing the physiological effects of microgravity].

Effectiveness of the countermeasures and methods for mitigation of the unfavorable effects of microgravity on mineral turnover and properties of bones was evaluated in simulation experiments with animals (penal immobilization, suspension) and with participation of human subjects (37 to 120-d head-down bed rest). The experiments with rats were aimed at testing pharmaceutical preparations (bisphosphonates), determining doses, plan and way of administration. Preparations of this group differ considerably in their action on osteogenesis, mostly because of specifics of the chemical structure. Nonetheless, optimization of the course of treatment masked significantly side effects without detriment to the preventive action. Head-down bed rest was used to test effectiveness of physical exercises (PE) as a main countermeasure against the microgravity impacts. Both standard and experimental PE regimens were tested. Several groups of test-subjects combined PE with consumption of xidifon (a bisphosphonate). In addition, mineral supplements (potassium and calcium) were used. The PE + xidifon combination and regulation of mineral intake with foods was found to reduce calcium losses during 370-d bed rest and prevent a material degradation of strength of bone samples, and essentially rehabilitate shifts in the hormonal regulation of calcium turnover and calciuretic function of the kidney.

Animals↗

Staying in bed to benefit ESA's astronauts and Europe's citizens.

Since Yuri Gagarin's historic first flight into space in April 1961, it has quickly become evident that the space environment influences the human body in many different ways and causes it to adapt in ways that can lead to problems when returning to Earth's gravity. Much research has been performed in the meantime and our understanding of what happens to our bodies in space improved considerably during the Mir space station and Space Shuttle/Spacelab era. However, many questions, particularly regarding how to counteract those changes that we now know take place, still need to be addressed through studies on the International Space Station (ISS) and through simulations on the ground. As we enter an era in which crews will spend longer periods in space on the ISS and of longer term plans by almost every space-faring nation for missions to Mars, it is clear that much more knowledge is needed, and quickly. Although a few hundred men and women have already travelled into space, the operating environment severely limits the amount of systematic research that can be performed--a situation that is unlikely to change. Other avenues for addressing specific scientific questions in a controlled research environment must therefore be found. One of these complementary alternatives is head-down-tilt bed-rest studies in which volunteers are confined to beds that are tilted -6 deg below the horizontal at the head end. Every activity, including eating, reading, showering, etc., is performed in this position for the duration of the study. This leads to changes in the human body that are very similar to those seen during spaceflight, such as bone-mass and muscle-mass loss, cardiovascular and neuro-sensory deconditioning. The controlled bed-rest setting therefore allows meaningful research into the bodily consequences of spaceflight and possible countermeasures. It also gives the scientific community interested in space-related medical research more ready access to a clinical model. The benefits of these studies go far beyond their space application. Patients bed-ridden because of illness or accidents suffer the same symptoms and can thus also profit from the studies. As a clear indication of this link, the clinicians and researchers involved in the bed-rest campaigns typically spend the majority of their time exploring "terrestrial" problems.

Adaptation, Physiological↗

Daily 4-h head-up tilt is effective in preventing muscle but not bone atrophy due to simulated microgravity.

To assess the potential value of intermittent artificial gravity as an efficient countermeasure, our previous studies have showed that daily 4-h standing (STD) is sufficient in counteracting muscle atrophy but not bone atrophy induced by simulated microgravity. The aim of the present study was to determine whether intermittent gravitational loading by daily 2-h or 4-h, +45 degrees head-up tilt (HUT) is more effective than STD in counteracting muscle and, particularly, bone atrophy due to simulated microgravity. Sprague-Dawley male rats weighing 290-300 g were subjected to a 28-d tail-suspension to simulate microgravity deconditioning. Daily HUT for 2, or 4 h was used to provide intermittent gravitational loading in foot-ward and tail-ward directions. The results showed that 4 h/d HUT was sufficient, and 2 h/d was less effective, in preventing adverse changes in muscle weights, fiber types, and cross-sectional areas (CSA) of muscles due to a 28-d simulated microgravity. The % protections by 4 h/d HUT in maintaining the CSAs of type I fibers in soleus, medial and lateral gastrocnemius and extensor digitorum longus muscles were 103%, 82%, 102%, and 83%, respectively. However, according to changes in physical and mechanical properties of femur, daily 4-h HUT was ineffective in attenuating the adverse changes in bone due to a 28-d simulated microgravity. Reductions in wet, dry, and ash weights and decreases in mechanical strength of femur did not show significant improvement by daily 2-h or 4-h HUT. Taken together, the findings indicate that the countermeasure effectiveness of daily 2-h or 4-h HUT for muscles is comparable with that by daily STD with the same durations. Daily 4-h HUT, as 4-h STD, is also ineffective in attenuating adverse changes in bone mass, but seems partially effective in preventing declines in mechanical properties due to simulated microgravity.

Animals↗

Deconditioning during prolonged immersion and possible countermeasures.

Test subjects covered with a waterproof highly elastic cloth were exposed to 13-day water immersion up to the neck. They were divided into two groups. The first (control) group consisting of six persons was exposed to immersion alone and the second (experimental) group was exposed daily to accelerations of 0.6-2 Gz for 60-90 min during the last 6 days of immersion. Before and after immersion all the test subjects were exposed to +3 Gz for 5 min which served as a provocative test. These experiments give evidence that the use of dry immersion allows experimentation during prolonged immersion without concomitant complications. Variations in the physiological parameters (cardiovascular system, fluid-electrolyte balance, blood-coagulatory system) are indicative of the preventive effect of periodic accelerations during 13-day immersion.

Acceleration↗

Neuropsychological and emotional changes during simulated microgravity: effects of triiodothyronine alendronate, and testosterone.

INTRODUCTION: We present the results of a two-experiment study designed to evaluate the neurocognitive and psychological effects of six-degree head-down bedrest and pharmacologic interventions (3,5,3'-triiodothyronine; T3) implemented to enhance the muscle and bone atrophy associated with simulated microgravity. Subsequently, the effects of countermeasures (alendronate and testosterone) administered to retard or reverse these T3 plus bedrest enhanced atrophic changes, were evaluated. Each participant was tested weekly for 5 weeks during Bedrest or non-bedrest (Up) conditions with the Neurobehavioral Evaluation System 2 (NES2), the Symptom Check List 90 Revised (SCL-90-R), and the Coping Responses Inventory (CRI). Resultant data were subjected to repeated measures, between groups analysis of variance testing for all 82 neurocognitive and psychological test measures. RESULTS: In Experiment 1, participants in the Placebo-Bedrest condition performed better on several neurocognitive measures compared to participants in the T3-Up condition. However, participants in the Placebo-Bedrest condition also reported more confusion. In Experiment 2 (countermeasure trials), superior coordination was observed for participants in the Testosterone-T3 condition over those in the Alendronate-T3 condition, but just the opposite for reaction time. Also, testosterone and to a lesser degree, alendronate, were associated with less self-reported emotional distress than T3 plus bedrest alone. CONCLUSION: Triiodothyronine, alendronate, and testosterone each influence participant response to simulated microgravity. Between group differences for significant findings were substantial and averaged 1.62 standard deviations. Although the observed neurocognitive effects likely pose no immediate danger for research participants, the significantly greater level of self-reported psychological symptoms by T3-Placebo and Placebo-Bedrest treated participants is of clinical importance.

Adult↗

[Effect of extremity cuffs as a countermeasure against the cardiovascular deconditioning during 21 d head-down bedrest].

OBJECTIVE: To affirm the protective effect of inflated cuffs. METHOD: The protective effect against the cardiovascular deconditioning of inflated cuffs on the upper parts of thighs and arms during the 1st through 10th days of 21 d bedrest has been reported previously. The effect of the cuffs during the rest of the 21 d bedrest were studied in this paper. Five subjects in cuffs group whose orthostatic tolerance were well maintained continued bed rest for 7 d without inflated cuffs. For the last 4 days of this period, inflated cuffs were again applied. Orthostatic tolerance of subjects in cuffs group with and without cuffs were measured. RESULT: Two of the five subjects suffered orthostatic intolerance on the 17th day. No sign of orthostatic intolerance were observed by the end of bedrest. CONCLUSION: (1) the cardiovascular deconditioning developed when inflated cuffs were not used, and (2) the use of inflated cuffs for 4 d improves the orthostatic tolerance.

Adolescent↗

Mechanic stimulation of the soles support zones as a countermeasure of the contractile properties decline under microgravity conditions.

Decrease in muscle contractility is an inevitable consequence of exposure in microgravity. A wealth of currently accumulated facts is indicative of profound modifications in structure and function of the skeletal muscles in the absence of gravity. Investigations with humans during space flights of varying duration (L.I. Kakurin et al., 1971; I.B. Kozlovskaya et al., 1984, 1987, 1991;.), ground-based simulation studies (A.M. Genin et al., 1969; L.S. Grigorieva et al., 1983), and numerous experiments with animals (E.I. IIyina-Kakueva et al., 1979; O.M. Edgerton et al 1991; B.S. Shenkman et al., 1994) made it evident that removal of gravitational loading is fraught with significant reductions in the contractile properties of muscular fibers, especially noticeable in muscles-extensors. Results of ground-based simulation studies led to the hypothesis that changes in muscle contractility developing already after few days in microgravity conditions are consequent to reduction in support afferentation that plays an important role in initiation and maintenance of the activity of tonic motor units (A.V. Kirenskaya et al., 1986). In view of the above, an idea has been proposed to prevent losses in tonic muscles contractility by application of artificial support. Testing of this hypothesis was the theme of the present investigation.

Adult↗

Is there resetting of central venous pressure in microgravity?

In the early phase of the Space Shuttle program, NASA flight surgeons implemented a fluid-loading countermeasure in which astronauts were instructed to ingest eight 1-g salt tablets with 960 ml of water approximately 2 hours prior to reentry from space. This fluid loading regimen was intended to enhance orthostatic tolerance by replacing circulating plasma volume reduced during the space mission. Unfortunately, fluid loading failed to replace plasma volume in groundbased experiments and has proven minimally effective as a countermeasure against post-spaceflight orthostatic intolerance. In addition to the reduction of plasma volume, central venous pressure (CVP) is reduced during exposure to actual and groundbased analogs of microgravity. In the present study, we hypothesized that the reduction in CVP due to exposure to microgravity represents a resetting of the CVP operating point to a lower threshold. A lower CVP 'setpoint' might explain the failure of fluid loading to restore plasma volume. In order to test this hypothesis, we conducted an investigation in which we administered an acute volume load (stimulus) and measured responses in CVP, plasma volume and renal functions. If our hypothesis is true, we would expect the elevation in CVP induced by saline infusion to return to its pre-infusion levels in both HDT and upright control conditions despite lower vascular volume during HDT. In contrast to previous experiments, our approach is novel in that it provides information on alterations in CVP and vascular volume during HDT that are necessary for interpretation of the proposed CVP operating point resetting hypothesis.

Aerospace Medicine↗

[Countermeasuring effect of lower body negative pressure against orthostatic intolerance induced by 21 d -6 degrees head down tilt in humans].

Objective. To investigate whether LBNP during 21 d -6 degrees head-down tilt (HDT) would modify orthostatic tolerance. Method. 12 healthy males, age 23.7 +/- 5.0, were exposed to -6 degrees HDT for 21 d. 6 of them received -4.0 kPa LBNP sessions for 1 h/d from 15th day to 21st day of HDT. The other 6 served as control. HUT + 75 degrees, 20 min orthostatic tolerance test were done before, on day 10 and on day 21 of HDT. Result. During HUT + 75 degrees, 20 min orthostatic tolerance test on day 10 of HDT, 5 subjects of the control group and 4 of the LBNP group presented presyncopal or syncopal signs and symptoms, the average standing time of both groups were shorter than those of the pre-HDT (p<0.05). During HUT + 75 degrees, 20 min orthostatic tolerance test on day 21 of HDT, 5 subjects of the control group and one subject of the LBNP group presented presyncopal or syncopal signs and symptoms, the average standing time of control group reduced significantly as compared with those of pre-HDT(P<0.05), also significantly shorter than those of LBNP group (P<0.05). Conclusion. The present study clearly shows that the use of LBNP could alleviate the bed rest-induced orthostatic intolerance.

Adult↗