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PubMed1986

Skeletal response to dietary calcium in a rat model simulating weightlessness.

Unweighting the hindlimbs of a rat by tail suspension leads to a decrease in bone in the unweighted hindlimbs, but not in the normally weighted forelimbs. We evaluated whether increments in dietary calcium could prevent this. Growing rats were fed diets ranging in calcium content from 0.1% to 2.4%. After the rats were suspended for two weeks, we found no differences between suspended and control animals fed the same diet with respect to calcium transport or serum levels of calcium, phosphorus, 1,25-dihydroxyvitamin D, and parathyroid hormone. In both groups, increasing dietary calcium reduced active intestinal calcium transport and serum 1,25-dihydroxyvitamin D levels. The calcium content of the tibia and lumbar vertebra (but not the humerus) was reduced in suspended rats compared to control rats fed the same diet. However, increasing dietary calcium increased the calcium content of all bones in both suspended and control animals. The bone formation rate at the tibiofibular junction (measured by double-label tetracycline) was reduced in the suspended animals compared to controls and was not altered by dietary calcium. However, the marrow area of the tibia, an indication of bone resorption, did not differ between suspended and control animals and was equally reduced in both groups when dietary calcium was increased. Our data suggest that the deleterious effects of skeletal unweighting on bone formation cannot be explained by changes in the calciotropic hormones and are not reversed by increments in dietary calcium. However, increasing dietary calcium can increase bone calcium, even in unweighted limbs, by decreasing bone resorption.

Animals↗
PubMed1993

Changes in markers of bone formation and resorption in a bed rest model of weightlessness.

To study the mechanism of bone loss in physical unloading, we examined indices of bone formation and bone resorption in the serum and urine of eight healthy men during a 7 day -6 degrees head-down tilt bed rest. Prompt increases in markers of resorption--pyridinoline (PD), deoxypyridinoline (DPD), and hydroxyproline (Hyp)/g creatinine--during the first few days of inactivity were paralleled by tartrate-resistant acid phosphatase (TRAP) with significant increases in all these markers by day 4 of bed rest. An index of formation, skeletal alkaline phosphatase (SALP), did not change during bed rest and showed a moderate 15% increase 1 week after reambulation. In contrast to SALP, serum osteocalcin (OC) began increasing the day preceding the increase in Hyp, remained elevated for the duration of the bed rest, and returned to pre-bed rest values within 5 days of reambulation. Similarly, DPD increased significantly at the onset of bed rest, remained elevated for the duration of bed rest, and returned to pre-bed rest levels upon reambulation. On the other hand, the other three indices of resorption, Hyp, PD, and TRAP, remained elevated for 2 weeks after reambulation. The most sensitive indices of the levels of physical activity proved to be the noncollagenous protein, OC, and the collagen crosslinker, DPD. The bed rest values of both these markers were significantly elevated compared to both the pre-bed rest values and the post-bed rest values. The sequence of changes in the circulating markers of bone metabolism indicated that increases in serum OC are the earliest responses of bone to head-down tilt bed rest.

Acid Phosphatase↗
PubMed1997

Prolonged weightlessness affects promyelocytic multidrug resistance.

An immortalized promyelocytic cell line was studied to detect how doxorubicin uptake is affected by microgravity. The purpose of this experiment was to identify the effect that microgravity may have on multidrug resistance in leukocytes. HL60 cells and HL60 cells resistant to anthracycline (HL60/AR) were grown in RPMI and 10% FBS. Upon reaching orbit in the Space Shuttle Endeavour, the cells were robotically mixed with doxorubicin. Three days after mixing, cells were fixed with paraformaldehyde/glutaraldehyde. Ground control experiments were conducted concurrently using a robot identical to the one used on the Shuttle. Fixed cells were analyzed within 2 weeks of launch. Confocal micrographs identified changes in cell structure (transmittance), drug distribution (fluorescence), and microtubule polymerization (fluorescence). Flight cells showed a lack of cytoskeletal polymerization resulting in an overall amorphic globular shape. Doxorubicin distribution in ground cells included a large numbers of vesicles relative to flight cells. There was a greater amount of doxorubicin present in flight cells (85% +/- 9.7) than in ground control cells (43% +/- 26) as determined by image analysis. Differences in microtubule formation between flight cells and ground cells could be partially responsible for the differences in drug distribution. Cytoskeletal interactions are critical to the function of P-glycoprotein as a drug efflux pump responsible for multidrug resistance.

Biological Transport↗
PubMed1986

M.I.T./Canadian vestibular experiments on the Spacelab-1 mission: 6. Vestibular reactions to lateral acceleration following ten days of weightlessness.

Tests of otolith function were performed pre-flight and post-flight on the science crew of the first Spacelab Mission with a rail-mounted linear acceleration sled. Four tests were performed using horizontal lateral (y-axis) acceleration: perception of linear motion, a closed loop nulling task, dynamic ocular torsion, and lateral eye deviations. The motion perception test measured the time to detect the onset and direction of near threshold accelerations. Post-flight measures of threshold and velocity constant obtained during the days immediately following the mission showed no consistent pattern of change among the four crewmen compared to their pre-flight baseline other than an increased variability of response. In the closed loop nulling task, crewmen controlled the motion of the sled and attempted to null a computer-generated random disturbance motion. When performed in the light, no difference in ability was noted between pre-flight and post-flight. In the dark, however, two of the four crewmen exhibited somewhat enhanced performance post-flight. Dynamic ocular torsion was measured in response to sinusoidal lateral acceleration which produces a gravitionertial stimulus equivalent to lateral head tilt without rotational movement of the head. Results available for two crewmen suggest a decreased amplitude of sinusoidal ocular torsion when measured on the day of landing (R+0) and an increasing amplitude when measured during the week following the mission.

Acceleration↗
PubMed1988

Adaptive modifications of postural attitude in conditions of weightlessness.

Adaptation of static posture was studied before, during, and after a 7-day space flight. Body segment orientations, body stability, and muscle activity underlying the reproduction of several postural attitudes were examined in various visual situations either with the shoes attached to the floor or during free floating. In standing or relaxed subjects whose shoes were attached to the floor, the tonic activity of the ankle flexor was enhanced relative to that in the same posture on earth, whereas the extensor activity disappeared. Errors in attempting to reproduce the normal terrestrial upright posture and a forward-leaning posture were accompanied by major changes in the synergies between neck, hip, knee, and ankle joints. These changes are mainly attributed to cumulative adjustments in response to nonvestibular signals such as tactile, articular, and proprioceptive cues.

Biomechanical Phenomena↗
PubMed1995

Contractile properties of the human triceps surae muscle during simulated weightlessness.

The effect of a 120-day period of bed rest on the mechanical properties of human triceps surae muscle was studied in a group of male volunteers (n = 6, mean age 38 years). The results shows that the contractile properties of skeletal muscle in response to disuse change considerably. Time to isometric peak tension of the triceps surae muscle increased from 120 (SEM 3.0)ms to 136 (SEM 2.9)ms (P < 0.01), half relaxation time from 92 (SEM 2.1)ms to 100 (SEM 1.6)ms (P < 0.05) and total contraction time from 440 (SEM 9.9)ms to 540 (SEM 18.7)ms (P < 0.001). Isometric twitch force (Ft) decreased by a mean of 36.7% (P < 0.05), maximal voluntary contraction (MVC) and maximal force (Fmax) by a mean of 45.5% and 33.7%, respectively (P < 0.05-0.01). The value Fmax:Ft ratio increased by 3.6% (nonsignificant). The difference between Fmax and MVC, expressed as a percentage of Fmax and referred to as force deficiency, has also been calculated. Force deficit increased by a mean of 60% (P < 0.001) after bed rest. Force-velocity properties of the triceps surae muscle calculated according to an absolute scale of voluntary and electrically evoked contraction development decreased considerably. The calculations of the same properties on a relative scale did not differ substantially from the initial physiological state. The results would suggest that muscle disuse is associated with both atrophy and a reduction in contractility in the development of Fmax and decreased central (motor) drive. The change in the triceps surae muscle contractile velocity properties may indicate changes in the kinetically active state in the muscles.

Adult↗
PubMed1997

Voluntary head stabilization in space during oscillatory trunk movements in the frontal plane performed in weightlessness.

The ability voluntarily to stabilize the head in space during lateral rhythmic oscillations (0.59+/-0.09 Hz) of the trunk has been investigated during microgravity (microG) and normal gravity (nG) conditions (parabolic flights). Five healthy young subjects, who gave informed consent, were examined. The movements were performed with eyes open or eyes closed, during phases of either microG or nG. The main result was that head orientation with respect to vertical may be stabilized about the roll axis under microG with, as well as without vision, despite the reduction in vestibular afferent and muscle proprioceptive inputs. Moreover, the absence of head stabilization about the yaw axis confirms that the degrees of freedom of the neck can be independently controlled, as was previously reported. These results seem to indicate that voluntary head stabilization does not depend crucially upon static vestibular afferents. Head stabilization in space may in fact be organized on the basis of either dynamic vestibular afferents or a short-term memorized postural body schema.

Acoustic Stimulation↗
PubMed2000

Moving weightless objects. Grip force control during microgravity.

When we move grasped objects, our grip force precisely anticipates gravitational and inertial loads. We analysed the control of grip forces during very substantial load changes induced by parabolic flights. During these flight manoeuvres, the gravity varies between hypergravity associated with a doubling of normal terrestrial gravity and a 20-s period of microgravity. Accordingly, the contribution of the object's weight to the load changed from being twice the normal value to being absent. Two subjects continuously performed vertical and horizontal movements of an object equipped with grip force and acceleration sensors. Whereas, during vertical movements performed under normal and hypergravity, a load force maximum occurred at the lower turning point and a minimum at the upper turning point, the load force pattern was completely changed under microgravity. In particular, the upper turning point was also associated with a load force maximum. Analysis of the grip forces produced by the two subjects revealed that the grip forces underwent the same characteristic changes as the load forces. Thus, subjects were able to adjust grip forces in anticipation of arm movement-induced fluctuations in load force under different and novel load conditions. Adaptation to changing levels of gravity was also obvious when the vertical and horizontal movements were compared: grip forces depended heavily on movement direction during normal and hypergravity but not during microgravity. The predictive coupling of grip force and load force was observed even during transitions between gravity levels, indicating rapid adaptation to changing load conditions. To account for the striking preservation of the normal characteristics of grip force control, we suggest that a highly automatized, extremely flexible sensorimotor mechanism firmly implemented within the central nervous system can cope with even massive changes in the environmental conditions.

Adaptation, Physiological↗
PubMed2000

Are energy metabolism alterations involved in cardiovascular deconditioning after weightlessness? An hypothesis.

The physiopathogenesis of the cardiovascular deconditioning syndrome observed after actual and simulated microgravity is still under debate, despite numerous studies conducted on the role of blood volume, hormones involved in its regulation, sympathetic nervous system, baroreflexes and venous compliance. Orthostatic intolerance, a reduced exercise capacity and an increased heart rate at rest characterize this syndrome. Recent data suggest, first, the presence of a complex loop between the sympathetic nervous system, carbohydrate metabolism (insulin) and leptin hormone and, second, that this loop, an overall reflection of energy metabolism, participates in cardiovascular regulation. After a resume of studies conducted on fuel homeostasis during actual and simulated microgravity, the possible implications of energy metabolism in the development of the cardiovascular deconditioning syndrome will be discussed.

Adaptation, Physiological↗