Pressure-distension relationship in arteries and arterioles in response to 5 wk of horizontal bedrest

We hypothesized that exposure to prolonged recumbency (bedrest), and thus reductions of intravascular pressure gradients, increases pressure distension in arteries/arterioles in the legs. Ten subjects underwent 5 wk of horizontal bedrest. Pressure distension was investigated in arteries and arterioles before and after the bedrest, with the subject seated or supine in a hyperbaric chamber with either one arm or a lower leg protruding through a hole in the chamber door. Increased pressure in the vessels of the arm/leg was accomplished by increasing chamber pressure. Vessel diameter and flow were measured in the brachial and posterior tibial arteries using Doppler ultrasonography. Electrical tissue impedance was measured in the test limb. Bedrest increased (P < 0.01) pressure distension threefold in the tibial artery (from 8 +/- 7% to 24 +/- 11%) and by a third (P < 0.05) in the brachial artery (from 15 +/- 9% to 20 +/- 10%). The pressure-induced increase in tibial artery flow was more pronounced (P < 0.01) after (50 +/- 39 ml/min) than before (13 +/- 23 ml/min) bedrest, whereas the brachial artery flow response was unaffected by bedrest. The pressure-induced decrease in tissue impedance in the leg was more pronounced (P < 0.01) after (16 +/- 7%) than before (10 +/- 6%) bedrest, whereas bedrest did not affect the impedance response in the arm. Thus, withdrawal of the hydrostatic pressure gradients that act along the blood vessels in erect posture markedly increases pressure distension in dependent arteries and arterioles.     

Assessment of Lumbar Intervertebral Disc Glycosaminoglycan Content by Gadolinium-Enhanced MRI before and after 21-Days of Head-Down-Tilt Bedrest

During spaceflight, it has been shown that intervertebral discs (IVDs) increase in height, causing elongation of the spine up to several centimeters. Astronauts frequently report dull lower back pain that is most likely of discogenic origin and may result from IVD expansion. It is unknown whether disc volume solely increases by water influx, or if the content of glycosaminoglycans also changes in microgravity. Aim of this pilot study was to investigate effects of the spaceflight analog of bedrest on the glycosaminoglycan content of human lumbar IVDs. Five healthy, non-smoking, male human subjects of European descent were immobilized in 6° head-down-tilt bedrest for 21 days. Subjects remained in bed 24 h a day with at least one shoulder on the mattress. Magnetic Resonance Imaging (MRI) scans were taken according to the delayed gadolinium-enhanced magnetic resonance imaging (dGEMRIC) protocol before and after bedrest. The outcome measures were T₁ and ΔT₁. Scans were performed before and after administration of the contrast agent Gd-DOTA, and differences between T₁-values of both scans (ΔT₁) were computed. ΔT₁ is the longitudinal relaxation time in the tissue and inversely related to the glycosaminoglycan-content. For data analysis, IVDs L1/2 to L4/5 were semi-automatically segmented. Zones were defined and analyzed separately. Results show a highly significant decrease in ΔT₁ (p<0.001) after bedrest in all IVDs, and in all areas of the IVDs. The ΔT₁-decrease was most prominent in the nucleus pulposus and in L4/5, and was expressed slightly more in the posterior than anterior IVD. Unexpected negative ΔT₁-values were found in Pfirrmann-grade 2-discs after bedrest. Significantly lower T₁ before contrast agent application was found after bedrest compared to before bedrest. According to the dGEMRIC-literature, the decrease in ΔT₁ may be interpreted as an increase in glycosaminoglycans in healthy IVDs during bedrest. This interpretation seems contradictory to previous findings in IVD unloading.     

Loss and re-adaptation of lumbar intervertebral disc water signal intensity after prolonged bedrest

The adaptation and re-adaptation process of the intervertebral disc (IVD) to prolonged bedrest is important for understanding IVD physiology and IVD herniations in astronauts. Little information is available on changes in IVD composition. In this study, 24 male subjects underwent 60-day bedrest and In/Out Phase magnetic resonance imaging sequences were performed to evaluate IVD shape and water signal intensity. Scanning was performed before bedrest (baseline), twice during bedrest, and three, six and twenty-four months after bedrest. Area, signal intensity, average height, and anteroposterior diameter of the lumbar L3/4 and L4/5 IVDs were measured. At the end of bedrest, disc height and area were significantly increased with no change in water signal intensity. After bedrest, we observed reduced IVD signal intensity three months (p=0.004 versus baseline), six months (p=0.003 versus baseline), but not twenty-four months (p=0.25 versus baseline) post-bedrest. At these same time points post-bedrest, IVD height and area remained increased. The reduced lumbar IVD water signal intensity in the first months after bedrest implies a reduction of glycosaminoglycans and/or free water in the IVD. Subsequently, at two years after bedrest, IVD hydration status returned towards pre-bedrest levels, suggesting a gradual, but slow, re-adaptation process of the IVD after prolonged bedrest.     

Caloric Restriction Decreases Orthostatic Tolerance Independently from 6° Head-Down Bedrest

Astronauts consume fewer calories during spaceflight and return to earth with an increased risk of orthostatic intolerance. Whether a caloric deficiency modifies orthostatic responses is not understood. Thus, we determined the effects of a hypocaloric diet (25% caloric restriction) during 6° head down bedrest (an analog of spaceflight) on autonomic neural control during lower body negative pressure (LBNP). Nine healthy young men completed a randomized crossover bedrest study, consisting of four (2 weeks each) interventions (normocaloric bedrest, normocaloric ambulatory, hypocaloric bedrest, hypocaloric ambulatory), each separated by 5 months. Muscle sympathetic nerve activity (MSNA) was recorded at baseline following normocaloric and hypocaloric interventions. Heart rate (HR) and arterial pressure were recorded before, during, and after 3 consecutive stages (7 min each) of LBNP (-15, -30, -45 mmHg). Caloric and posture effects during LBNP were compared using two-way ANOVA with repeated measures. There was a strong trend toward reduced basal MSNA following caloric restriction alone (normcaloric vs. hypocaloric: 22±3 vs. 14±4 burst/min, p = 0.06). Compared to the normocaloric ambulatory, both bedrest and caloric restriction were associated with lower systolic blood pressure during LBNP (p<0.01); however, HR responses were directionally opposite (i.e., increase with bedrest, decrease with caloric restriction). Survival analysis revealed a significant reduction in orthostatic tolerance following caloric restriction (normocaloric finishers: 12/16; hypocaloric finishers: 6/16; χ2, p = 0.03). Caloric restriction modifies autonomic responses to LBNP, which may decrease orthostatic tolerance after spaceflight.     

Renal responsiveness to aldosterone during exposure to head-down tilt bedrest

The kidneys represent a fundamental organ system responsible in part for the control of vascular volume. A 10% to 20% reduction in plasma volume is one of the fundamental adaptations during exposure to low gravity environments such as bedrest and space flight. Bedrest-induced hypovolemia has been associated with acute diuresis and natriuresis. Elevated baseline plasma renin activity and aldosterone levels have been observed in human subjects following exposure to head-down tilt and spaceflight without alterations in renal sodium excretion. Further, attempts to restore plasma volume with isotonic fluid drinking or infusion in human subjects exposed to head-down bedrest have failed. One explanation for these observations is that renal distal tubular cells may become less sensitive to aldosterone following exposure to head-down tilt, with a subsequent reduction in renal capacity for sodium retention. We hypothesized that elevated sodium and water excretion observed during prolonged exposure to bedrest and the subsequent inability to restore body fluids by drinking might be reflected, at least in part, by reduced renal tubular responsiveness to aldosterone. If renal tubular responsiveness to aldosterone were reduced with confinement to bedrest, then we would expect measures of renal sodium retention to be reduced when a bolus of aldosterone was administered in head-down tilt (HDT) bedrest compared to a control experimental condition. In order to test this hypothesis, we conducted an investigation in which we administered an acute bolus of aldosterone (stimulus) and measured responses in renal functions that included renal clearances of sodium and free water, sodium/potassium ratio in urine, urine sodium concentration, and total and fractional renal sodium excretion.     

Masking of the circadian rhythms of heart rate and core temperature by the rest-activity cycle in man

Heart rate and core temperature are elevated by physical activity and reduced during rest and/or sleep. These masking effects may confound interpretation of rhythm waveforms, particularly in situations where the rest-activity rhythm has a different period from that of the core temperature rhythm. Such desynchronization often occurs temporarily as an individual adjusts to a new work shift or to a new time zone following rapid transmeridian travel, making it difficult to assess the impact of such schedule changes on the circadian system. The present experiments were designed to estimate the magnitude of these masking effects, by monitoring the heart rate, rectal temperature, and nondominant wrist activity (2-min samples) of 12 male subjects during 6 days of normal routine outside the lab and during 6 days of strict bedrest. Subjects also kept sleep, dietary, and exercise logs throughout the study. Average (20-min) waveforms were computed for each subject and each rhythm, at home and in bedrest. In addition, data were partitioned according to self-reported sleep and wake times and were analyzed separately for each state. Average waveform comparisons indicated that about 45% of the range of the circadian heart rate rhythm during normal routine was attributable to the masking effects of activity during wake, which also produced a 16% elevation in mean heart rate during wake and an 11% increase in mean heart rate overall. (Analysis of variance indicated that mean heart rate during sleep at home was not significantly different from the mean during sleep in bedrest.) On average, about 14% of the range of the circadian temperature rhythm during normal routine was attributable to the effects of activity masking. However, the change in range of the temperature rhythm, from home to bedrest, was very variable between subjects (-41% to +13%). This variability was not accounted for by age or by reported frequency of exercise at home. Normal activity during wake increased the mean temperature during wake by an average of 0.16 degrees C and the overall mean by about 0.12 degrees C. (Analysis of variance indicated that mean temperature during sleep at home was not significantly different from the mean during sleep in bedrest.) A 10-hr "night" (lights-off from 2200 to 0800 hr) was provided during bedrest, within which subjects could select their own sleep times. Times of sleep onset and wake onset were not significantly different between home and bedrest.(ABSTRACT TRUNCATED AT 400 WORDS)     

Haemodynamics of leg veins during a 30-days-6 degrees head-down bedrest with and without lower body negative pressure

Venous distensibility of the lower limbs was assessed in six healthy men who were submitted twice successively to 1 month of -6 degrees head-down bedrest, with and without lower body negative pressure (LBNP) (LBNP subjects and control subjects, respectively). Venous capacity (delta Vv,max, in ml.100 ml-1) of the legs was determined by mercury strain gauge plethysmography with venous occlusion. Plethysmographic measurements were made on each subject before (Dc), during (D6 and D20) and after (5th day of recovery, D+5) bedrest. During bedrest, LBNP was applied daily, several times a day to the subjects submitted to this procedure. Results showed a gradual increase in Vv,max (ml.100 ml-1) throughout the bedrest, both in the control group [delta Vv,max = 2.11 SD 0.54 at Dc, 2.69 SD 0.29 at D6, 4.39 SD 2.08 at D20, 2.39 SD 0.69 at D+5, P less than 0.001 (ANOVA)] and in the LBNP group [delta Vv,max = 2.07 SD 0.71 at Dc, 2.85 SD 1.19 at D6, 3.75 SD 1.74 at D20, 2.43 SD 0.94 at D+5, P less than 0.001 (ANOVA)], without significant LBNP effect. These increases were of the same order as those encountered during spaceflight. It is concluded that -6 degrees head-down bedrest is a good model to simulate the haemodynamic changes induced by exposure to weightlessness and that LBNP did not seem to be a good technique to counteract the adverse effects of weightlessness on the capacitance vessels of the lower limbs. This latter conclusion raises the question of the role and magnitude of leg venous capacitance in venous return and cardiac regulation.     

Differential atrophy of the postero-lateral hip musculature during prolonged bedrest and the influence of exercise countermeasures

As part of the 2nd Berlin BedRest Study (BBR2-2), we investigated the pattern of muscle atrophy of the postero-lateral hip and hamstring musculature during prolonged inactivity and the effectiveness of two exercise countermeasures. Twenty-four male subjects underwent 60 days of head-down tilt bedrest and were assigned to an inactive control (CTR), resistive vibration exercise (RVE), or resistive exercise alone (RE) group. Magnetic resonance imaging (MRI) of the hip and thigh was taken before, during, and at end of bedrest. Volume of posterolateral hip and hamstring musculature was calculated, and the rate of muscle atrophy and the effect of countermeasure exercises were examined. After 60 days of bedrest, the CTR group showed differential rates of muscle volume loss (F = 21.44; P ≤ 0.0001) with fastest losses seen in the semi-membranosus, quadratus femoris and biceps femoris long head followed by the gluteal and remaining hamstring musculature. Whole body vibration did not appear to have an additional effect above resistive exercise in preserving muscle volume. RE and RVE prevented and/or reduced muscle atrophy of the gluteal, semi-membranosus, and biceps femoris long head muscles. Some muscle volumes in the countermeasure groups displayed faster recovery times than the CTR group. Differential atrophy occurred in the postero-lateral hip musculature following a prolonged period of unloading. Short-duration high-load resistive exercise during bedrest reduced muscle atrophy in the mono-articular hip extensors and selected hamstring muscles. Future countermeasure design should consider including isolated resistive hamstring curls to target this muscle group and reduce the potential for development of muscle imbalances.     

Erythropoietin in blood volume regulation under real and simulated micro-g conditions

Changes in erythropoietin levels in the blood were measured under several experimental conditions. Subjects were exposed to either bedrest, isolation and confinement, head-down tilt, or space flight. Results indicated that production and release of erythropoietin were decreased following simulated weightlessness and in some space flown subjects. The authors conclude that the responses are much more individual in space than during simulation experiments.     

Neuromuscular adaptations during 30 days of cast-immobilization and head-down bedrest

Prolonged skeletal muscle disuse, during space flights and on Earth, produces distinct adaptive changes in the neuromuscular system of human subjects. There is a significant decline in muscle mass and strength, exercise capacity, fatigue resistance, integrated EMG (IEMG) output and time-dependent alterations in the behavior of Hoffman (H) and deep tendon reflexes. The objective of this study was to examine the changes in excitability of segmental motoneuronal network and its influence upon gastrocnemius-soleus (G-S) function in healthy male and female subjects, who underwent either 6 degrees head-down bedrest (HDB) or unilateral cast-immobilization (CIM) for a period of 30 days.     

Effects of LBNP + specific physical exercises on leg venous hemodynamics during a 28-days -6 degrees head-down bedrest

The mechanisms underlying increased venous distensibility during exposure to microgravity are not well known yet. However, there seems to be evidence indicating that skeletal muscle changes resulting from exposure to microgravity play a very important role. The purpose of this experiment was to test the hypothesis that leg muscles could play an important role in the changes of leg venous distensibility observed in simulated microgravity. Twelve subjects were submitted for 28 days to a -6 degrees head-down bedrest. Changes in leg vein hemodynamics (filling and emptying) have been measured by mercury strain gauge plethysmography with venous occlusion. Six of these subjects trained their lower limbs with isometric and isokinetic exercises during bedrest (group CM), while the other 6 subjects (control group, C) had no training.     

Effects of normobaric hypoxic bed rest on the thermal comfort zone

Future Lunar and Mars habitats will maintain a hypobaric hypoxic environment to minimise the risk of decompression sickness during the preparation for extra-vehicular activity. This study was part of a larger study investigating the separate and combined effects of inactivity associated with reduced gravity and hypoxia, on the cardiovascular, musculoskeletal, neurohumoural, and thermoregulatory systems. Eleven healthy normothermic young male subjects participated in three trials conducted on separate occasions: (1) Normobaric hypoxic ambulatory confinement, (2) Normobaric hypoxic bedrest and (3) Normobaric normoxic bedrest. Normobaric hypoxia was achieved by reduction of the oxygen fraction in the air (F_iO₂=0.141±0.004) within the facility, while the effects of reduced gravity were simulated by confining the subjects to a horizontal position in bed, with all daily routines performed in this position for 21 days. The present study investigated the effect of the interventions on behavioural temperature regulation. The characteristics of the thermal comfort zone (TCZ) were assessed by a water-perfused suit, with the subjects instructed to regulate the sinusoidally varying temperature of the suit within a range considered as thermally comfortable. Measurements were performed 5 days prior to the intervention (D-5), and on days 10 (D10) and 20 (D20) of the intervention. no statistically significant differences were found in any of the characteristics of the TCZ between the interventions (HAMB, HBR and NBR), or between different measurement days (D-5, D10, D20) within each intervention. rectal temperature remained stable, whereas skin temperature (T_sk) increased during all interventions throughout the one hour trial. no difference in T_sk between D-5, D10 and D20, and between HAMB, HBR and NBR were revealed. subjects perceived the regulated temperature as thermally comfortable, and neutral or warm. we conclude that regulation of thermal comfort is not compromised by hypoxic inactivity.     

Leg vein hemodynamics during bedrests simulating lunar trip

When contemplating future trips to the Moon whose gravity is one sixth of Earth gravity, the question is to know what the adaptive changes in the lower limb venous system would be. In fact, one can suppose that the presence of a partial gravity on the Moon would be able to attenuate venous hemodynamics adaptative changes observed in microgravity. In the present experiment changes in the venous hemodynamics of lower limbs have been studied with mercury strain gauge plethysmography during a simulated Moon mission including a 4 day trip to the Moon (-6 degrees bedrest), a stay of 6 days on the Moon (+11 degrees bedrest), and a 4-day trip back to Earth (-6 degrees bedrest). It was previously demonstrated that +11 degrees bedrest was a good model to simulate the effects of lunar gravity on the cardiovascular system (Vernikos-Danellis J 1986, personnal communication).     

Lumbo-pelvic joint protection against antigravity forces: motor control and segmental stiffness assessed with magnetic resonance imaging

The antigravity muscles of the lumbo-pelvic region, especially transversus abdominis (TrA), are important for the protection and support of the weightbearing joints. Measures of TrA function (the response to the postural cue of drawing in the abdominal wall) have been developed and quantified using magnetic resonance imaging (MRI). Cross-sections through the trunk allowed muscle contraction as well as the large fascial attachments of the TrA to be visualized. The cross sectional area (CSA) of the deep musculo-fascial system was measured at rest and in the contracted state, using static images as well as a cine sequence. In this developmental study, MRI measures were undertaken on a small sample of low back pain (LBP) and non LBP subjects. Results demonstrated that, in non LBP subjects, the draw in action produced a symmetrical deep musculo-fascial "corset" which encircles the abdomen. This study demonstrated a difference in this "corset" measure between subjects with and without LBP. These measures may also prove useful to quantify the effect of unloading in bedrest and microgravity exposure.     

Age dependency and correlation of heart rate variability,blood pressure variability and baroreflex sensitivity

Simultaneous analysis of heart rate variability (HRV), blood pressure variability (BPV) and baroreflex sensitivity (BRS) with different types of measures may provide non-duplicative information about autonomic cardiovascular regulation. Therefore, a multiple signal analysis of cardiovascular time series will enhance the physiological understanding of neuro cardiovascular regulation with deconditioning in bedrest or related gravitational physiological studies. It has been shown that age is an important determinant of HRV and BRS in healthy subjects. Whereas in the case of BPV, the effect of aging seems to depend upon the activity status of the subjects. In view of the facts that most of the previous works were dealing with only the variability of one kind of cardiovascular parameters in one study with conventional time-domain and/or frequency-domain analysis, we therefore designed the present work to compare the HRV, BPV and BRS between young and middle-aged male healthy subjects in one study with the same subjects using various techniques, including the approximate entropy (ApEn) measurement, a statistic quantifying HRV "complexity" derived from non-linear dynamics.     

Relations between visceral and behavioral function in men at bedrest

Multiple physiological measurements as well as a self-assessment of arousal was made in eight men on the first, third, and fifth days of bedrest. On the third day, additional measurements of performance on memory and dexterity tasks were made. Univariate analysis did not reveal any physiological variable to either predict subsequent performance well or to co-vary acutely with it; however, self-rating scores did prove to be useful predictors of subsequent performance. Principal components analysis suggested an "alertness" factor comprised of physiological measures as well as self-ratings which helped in predicting better performance. Although the individual patterns of correlations between variable on each of the three test days was variable, even more variability between subjects was found on the performance testing day. We believe this effect of behavioral activation may be due to the injection of common, slow temporal trends into many of the different data sets.     

Anthropological and clinical characteristics in adolescent women with dysmenorrhea

The aim of this study was to examine the prevalence of dysmenorrhea in female adolescents and the influence of anthropological characteristics and lifestyle factors on menstrual pain. Two hundred and ninety seven girls from several elementary and secondary schools were interviewed about the presence of the menstrual pain, their age, height and weight, menarcheal age, menstrual cycles quality, smoking and sexual activity. There were 164 (55%) subjects with and one hundred and thirty three (45%) without dysmenorrhea. The adolescents with dysmenorrhea answered the questions about missing activities and taking pills for pain. No difference was observed between the girls with and the girls without dysmenorrhea in their chronological age, height, weight, menarcheal age, menstrual cycles quality, cigarette smoking and sexual activity. In the group of dysmenorrheic adolescents there was infrequent missing activities and bedrest, but missing school was observed in 22 percent and taking pills for pain was observed in 96 percent of the subjects. Young girls who experienced menstrual pain are good candidates for a prophylactic therapy, such as hormonal contraception. A replication of this study is needed for public health services in the future to improve the quality of life of the dysmenorrheic young women.     

Conditional activation of akt in adult skeletal muscle induces rapid hypertrophy

Skeletal muscle atrophy is a severe morbidity caused by a variety of conditions, including cachexia, cancer, AIDS, prolonged bedrest, and diabetes. One strategy in the treatment of atrophy is to induce the pathways normally leading to skeletal muscle hypertrophy. The pathways that are sufficient to induce hypertrophy in skeletal muscle have been the subject of some controversy. We describe here the use of a novel method to produce a transgenic mouse in which a constitutively active form of Akt can be inducibly expressed in adult skeletal muscle and thereby demonstrate that acute activation of Akt is sufficient to induce rapid and significant skeletal muscle hypertrophy in vivo, accompanied by activation of the downstream Akt/p70S6 kinase protein synthesis pathway. Upon induction of Akt in skeletal muscle, there was also a significant decrease in adipose tissue. These findings suggest that pharmacologic approaches directed toward activating Akt will be useful in inducing skeletal muscle hypertrophy and that an increase in lean muscle mass is sufficient to decrease fat storage.     

Temporal artery flow response during the last minute of a head up tilt test, in relation with orthostatic intolerance after a 60 day head-down bedrest

Objective

Check if the Temporal flow response to Tilt could provide early hemodynamic pattern in the minutes preceding a syncope during the Tilt test performed after a 60-d head down bedrest (HDBR).

Method

Twenty-one men divided into 3 groups [Control (Con), Resistive Vibration (RVE) and Chinese Herb (Herb)] underwent a 60 day HDBR. Pre and Post HDBR a 20 min Tilt identified Finishers (F) and Non Finishers (NF). Cerebral (MCA), Temporal (TEMP), Femoral (FEM) flow velocity, were measured by Doppler during the Tilt. Blood pressure (BP) was measured by arm cuff and cardiopress.

Results and Discussion

Four of the 21 subjects were NF at the post HDBR Tilt test (Con gr:2, RVE gr: 1, Herb gr: 1). At 1 min and 10 s before end of Tilt in NF gr, FEM flow decreased less and MCA decreased more at post HDBR Tilt compared to pre (p<0.05), while in the F gr they changed similarly as pre. In NF gr: TEMP flow decreased more at post HDBR Tilt compared to pre, but only at 10 s before the end of Tilt (P<0.05). During the last 10 s a negative TEMP diastolic component appeared which induced a drop in mean velocity until Tilt arrest.

Conclusion

The sudden drop in TEMP flow with onset of a negative diastolic flow preceding the decrease in MCA flow confirm that the TEMP vascular resistance respond more directly than the cerebral one to the cardiac output redistribution and that this response occur several seconds before syncope.