[Cerebral vasoreactivity: Concordance of breath holding test and acetazolamide injection in current practice: 20 cases of asymptomatic carotid artery stenosis]. / Étude de la vasoréactivité cérébrale en Doppler transcrânien : évaluation du test d'apnée comparé à l'injection d'acetazolamide en soins courants. Exploration de 20 sténoses carotidiennes asymptomatiques.

INTRODUCTION: Cerebral vasoreactivity (CVR) is the ability of the brain's vascular system to keep cerebral blood inflow stable. Impaired CVR is a risk marker of stroke in patients with asymptomatic carotid stenosis. The gold standard to assess CVR with transcranial ultrasound is acetazolamide (ACTZ) injection. The breath holding test (BHT) might be easier to perform. CVR proved to be efficient in laboratory conditions but not in routine practice. OBJECTIVES: To study the validity of BHT versus ACTZ in routine practice in a vascular exploration unit in patients with asymptomatic carotid stenosis. METHODS: Study of concordance of BHT and ACTZ, to assess CVR in patients consecutively explored on the same day. RESULTS: Eighteen patients with 20 carotid stenosis were included. The temporal window was missing in 20% of cases. Only 11 out of the 20 procedures were analyzed. Concordance was low between BHT and ACTZ to assess CVR (k=0.3714). CONCLUSION: BHT cannot replace ACTZ injection. It might be a first-step test so that ACTZ injection might be avoided if CVR is normal. Our present results must be confirmed by further study enrolling many more patients.

A novel Osmium-based compound targets the mitochondria and triggers ROS-dependent apoptosis in colon carcinoma.

Engagement of the mitochondrial-death amplification pathway is an essential component in chemotherapeutic execution of cancer cells. Therefore, identification of mitochondria-targeting agents has become an attractive avenue for novel drug discovery. Here, we report the anticancer activity of a novel Osmium-based organometallic compound (hereafter named Os) on different colorectal carcinoma cell lines. HCT116 cell line was highly sensitive to Os and displayed characteristic features of autophagy and apoptosis; however, inhibition of autophagy did not rescue cell death unlike the pan-caspase inhibitor z-VAD-fmk. Furthermore, Os significantly altered mitochondrial morphology, disrupted electron transport flux, decreased mitochondrial transmembrane potential and ATP levels, and triggered a significant increase in reactive oxygen species (ROS) production. Interestingly, the sensitivity of cell lines to Os was linked to its ability to induce mitochondrial ROS production (HCT116 and RKO) as HT29 and SW620 cell lines that failed to show an increase in ROS were resistant to the death-inducing activity of Os. Finally, intra-peritoneal injections of Os significantly inhibited tumor formation in a murine model of HCT116 carcinogenesis, and pretreatment with Os significantly enhanced tumor cell sensitivity to cisplatin and doxorubicin. These data highlight the mitochondria-targeting activity of this novel compound with potent anticancer effect in vitro and in vivo, which could have potential implications for strategic therapeutic drug design.

[Evaluation of a proximity training program of nuchal translucency measurements and of self-scoring]. / Evaluation d'une formation de proximité à la mesure de la clarté nucale et à l'autoévaluation des clichés.

OBJECTIVE: Improvement in prenatal diagnosis of Down syndrome imposes to sonographers to realize good quality nuchal translucency measurements, which can be used for assessment of combined risk. The aim of our study was to evaluate a training program of 109 sonographers for measuring nuchal translucency and scoring their own image. STUDY DESIGN: After a proximity training program, trainees submitted 20 images scored by themselves with Herman image-scoring method. All images were reviewed by two experts. RESULTS: One hundred and nine sonographers have accomplished the training program (87.3%), collecting 2162 images. After reviewing, the mean score was 6.8+/-1.8. The rate of inacceptable scan (score< or =3) was in 6.0%. On the other hand, 48.1% of scans were excellent (score> or =8). Only 6.5% of scores were discordant for at least three points between self-scoring and reviewing. After the fourth scan, there was no significant scoring difference between self-scoring and reviewing. Finally, 84% of trainees were very satisfied of this program. CONCLUSION: As part of HAS evaluation of practitioners practices, it is possible to realize proximity training program for measuring nuchal translucency. Learning curve seems to be fast. Good handling of Herman scoring method by sonographers allows their accreditation after this kind of training program.

HUMEX, a study on the survivability and adaptation of humans to long-duration exploratory missions, part I: lunar missions.

The European Space Agency has recently initiated a study of the human responses, limits and needs with regard to the stress environments of interplanetary and planetary missions. Emphasis has been laid on human health and performance care as well as advanced life support developments including bioregenerative life support systems and environmental monitoring. The overall study goals were as follows: (i) to define reference scenarios for a European participation in human exploration and to estimate their influence on the life sciences and life support requirements; (ii) for selected mission scenarios, to critically assess the limiting factors for human health, wellbeing, and performance and to recommend relevant countermeasures; (iii) for selected mission scenarios, to critically assess the potential of advanced life support developments and to propose a European strategy including terrestrial applications; (iv) to critically assess the feasibility of existing facilities and technologies on ground and in space as testbeds in preparation for human exploratory missions and to develop a test plan for ground and space campaigns; (v) to develop a roadmap for a future European strategy towards human exploratory missions, including preparatory activities and terrestrial applications and benefits. This paper covers the part of the HUMEX study dealing with lunar missions. A lunar base at the south pole where long-time sunlight and potential water ice deposits could be assumed was selected as the Moon reference scenario. The impact on human health, performance and well being has been investigated from the view point of the effects of microgravity (during space travel), reduced gravity (on the Moon) and abrupt gravity changes (during launch and landing), of the effects of cosmic radiation including solar particle events, of psychological issues as well as general health care. Countermeasures as well as necessary research using ground-based test beds and/or the International Space Station have been defined. Likewise advanced life support systems with a high degree of autonomy and regenerative capacity and synergy effects were considered where bioregenerative life support systems and biodiagnostic systems become essential. Finally, a European strategy leading to a potential European participation in future human exploratory missions has been recommended.

Renal and hormonal responses to isotonic saline infusion after 3 days' head-down tilt vs. supine and seated positions.

AIM: The study aimed to determine whether prolonged exposure to simulated microgravity produces a level of thoracic volume receptor loading similar to that seen in the upright position or immediately after lying down. METHODS: We used a cross-over design to compare responses to a saline infusion in eight healthy subjects during a 4-day, -6 degree head-down tilt (HDT) and in the acute seated and acute supine positions. RESULTS: The first 24 h of HDT were associated with greater urinary excretion of water and sodium (UV, UNaV) than seated and acute supine [cumulative UV, 3035 +/- 219, 2311 +/- 156 (P < 0.05), and 2448 +/- 182 mL (P < 0.05), respectively; cumulative UNaV, 256 +/- 19, 180 +/- 11 (P < 0.05), and 189 +/- 15 mmol (P < 0.05), respectively]. Haemoglobin and haematocrit were increased after 24 h and plasma volume decreased after 48 h of HDT (P < 0.05). With prolongation of HDT, UV and UNaV returned near the baseline values, and plasma atrial natriuretic factor (ANF) and renin values returned to acute seated levels; in acute supine, ANF values were higher and renin lower than in the two other positions. After a 30-min infusion of 20 mL kg(-1) isotonic saline on the fourth HDT day or during acute seated or acute supine, sodium excretion within 4 h was similar during HDT and acute seated (83 +/- 6 and 84 +/- 9 mmol, respectively) and greater during supine (104 +/- 8 mmol, P < 0.05). The renin decrease was greater in HDT and seated than in supine. The plasma ANF increase was greater during HDT than during supine; during seated, plasma ANF was unchanged. CONCLUSION: These data suggest that, after 4 days of HDT, thoracic volume receptor loading returns to the same level as in the seated position, leading to blunted responses to volume expansion as compared with the acute supine position.

Clinical effects of thigh cuffs during a 7-day 6 degrees head-down bed rest.

Thigh cuffs are used by Russian cosmonauts to limit the fluid shift induced by space flight. A ground simulation using the head-down bed rest (HDBR) model was performed to assess the effects of thigh cuffs on clinical tolerance and orthostatic adaptation. 8 male healthy volunteers (32.4 +/- 1.9 years) participated twice in a 7-day HDBR--one time with thigh cuffs (worn daily from 9 am to 7 pm) (TC) and one time without (WTC). Orthostatic tolerance was assessed by a 10 minute stand test and by a LBNP test (5 min at -15, -30, -45 mmHg) before (BDC-1) and at the end of the HDBR period (R+1). Plasma volume was measured before and at the end of HDBR by the Evans blue dye dilution technique. Thigh cuffs limits headache due to fluid shift, as well as the loss in plasma volume (TC: -5.85 +/- 0.95%; WTC: -9.09 +/- 0.82%, p<0.05). The mean duration of the stand test (R+1) did not differ in the two group (TC 7.1 +/- 1.3 min; WTC 7.0 +/- 1.0 min). The increase in HR and decrease in diastolic blood pressure were slightly but significantly larger without thigh cuffs. Duration of the LBNP tests did not differ with thigh cuffs. Thigh cuffs limit the symptoms due to fluid shift and the loss in plasma volume. They partly reduced the increase in HR during orthostatic stress but had no effect on duration of orthostatic stress tests.

Enhanced flow-dependent vasodilatation after bed rest, a possible mechanism for orthostatic intolerance in humans.

We investigated the alteration in flow-dependent-dilatation in the orthostatic intolerance occurring after bed-rest deconditioning. Eight men [aged mean (SEM) 32 (2) years] underwent two consecutive periods of 7 days of head-down-tilt (HDT, -6 degrees) during bed rest. A control age and sex matched group [n = 8, 30 (2) years], maintained its usual physical activity. Blood flow velocity (BFV) and diameter (Doppler and echotracking systems) were measured in the brachial artery, under basal conditions and during the post ischaemic hyperaemia following occlusion. The increase in BFV post-ischaemia did not change before, during and after HDT but the relative increase in the diameter was greater on the 7th day of the HDT period than before HDT [+8.8(1.6)% compared to +3.7(1.0)%, P < 0.001]. After HDT, 11 of 16 standing tests (comprising eight subjects in the two HDT periods) had to be stopped because of orthostatic intolerance. The flow-dependent-dilatation measured at the end of HDT was negatively correlated with the post-bed-rest duration of orthostatic tolerance (r = 0.78, P < 0.01). After the sublingual administration of glyceryl trinitrate, there was no change in the increase in diameter. No significant changes were observed in the control group. Bed-rest deconditioning enhances the flow-dependent vasodilatation of large arteries and might contribute to the orthostatic intolerance observed following bed-rest.

Use of thigh pressure cuffs to modulate simulated microgravity-induced changes in the skin measured with high-resolution B-scan ultrasound.

OBJECTIVE: The aim of the present study was to evaluate the fluid shift in a simulated microgravity experiment and to test the use of thigh cuffs to help alleviate the problem. METHODS: The change in skin thickness was assessed by a 20 MHz B-scan ultrasound device. This was performed on eight volunteers who underwent two successive 7-day periods of -6 degrees anti-orthostatic bed-rest, with or without the daytime use of thigh cuffs. The thigh cuffs were used to counteract the development of facial oedema. RESULTS: In the control group (without thigh cuffs), the results showed a steady increase in skin thickness of the combined dermis and hypodermis of the forehead and a reduction of the thickness of this tissue on the tibia. For the countermeasure group, although thigh cuffs were only employed during the daytime - being removed at night - their use reduced the amplitude and kinetics of the fluid shift, resulting in greater beneficial effects at the end of the day than early in the morning. CONCLUSION: These results of objective measurements of skin made using a non-invasive high frequency ultrasonography method confirm reports by cosmonauts of a reduction in facial oedema and a more 'comfortable' adaptation to microgravity by the use of thigh cuffs during space flight. This system is potentially promising for investigating fluid shifts in the skin and may prove useful in the evaluation of some oedematous skin diseases, as well as their therapy.

Weightlessness as an accelerated model of nutritional disturbances.

Food intake and eating patterns, body functions and composition are significantly altered by short-duration space flight. Prolonged missions lasting weeks or months further aggravate these changes, and are responsible for acute or chronic physical impairments at return to ground conditions. Current projects of missions to Mars, resulting in 2 years of microgravity conditions, stress the critical need for the development of optimal nutritional programs and physical countermeasures to prevent body mass and function alterations. This review outlines ground models of microgravity simulation, summarizes the major effects of weightlessness on body composition, protein metabolism, hormonal pattern, and muscle function, and addresses contradictory findings related to the oxidative stress secondary to space flight. Potential countermeasures, such as nutrient intake and physical conditioning, as well as areas of interest for future research both in ground and space medicine, are discussed.

Endocrine responses to 7 days of head-down bed rest and orthostatic tests in men and women.

The objective of this study was to investigate plasma volume (PV), total body water, hormones and hydroelectrolyte responses in eight males (25-40 years) and eight females (25-31 years) during 7 days of exposure to simulated microgravity (-6 degrees head-down bed rest, HDBR). Bed rest is a model that has commonly been used to simulate spaceflight. Heart rate (HR), blood pressure (BP) and vasoactive hormone responses were studied before and after HDBR during a 10-min stand test. No change in total body water and body mass was noted in either sex. The decrease in PV was similar in both men (9.1 +/- 1.4%) and women (9.4 +/- 0.8%). Urinary normetanephrine (NMN) was decreased during HDBR in both sexes. Urinary metanephrine (MN) and plasma catecholamines were unchanged. Daily urinary excretion of urea, an indirect index of protein breakdown, was increased only in the female subjects during HDBR. Plasma active renin (AR) and aldosterone were increased in both sexes, but urinary atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) were unchanged throughout the study. Also, the hormonal responses to 7 days of HDBR were comparable between men and women. Moreover, the results show similar cardiovascular and endocrine responses to standing after HDBR. However, the orthostatic intolerance following HDBR was associated with a blunted increase in noradrenaline (NA) only in the women during the stand test. It is concluded that: (i) 7 days of physical inactivity achieved during HDBR resulted in a reduced sympathetic activity in both sexes and alterations in protein metabolism in women and (ii) standing after HDBR resulted in an attenuated release of noradrenaline in women.

Effect of prolonged head-down bed rest on complex cardiovascular dynamics.

We postulated that a change in complex dynamics of the cardiovascular system could be involved in the orthostatic intolerance observed after simulated weightlessness. Supine recordings of 1024 consecutive pulse intervals and systolic blood pressures were obtained on 7 subjects adapted to a 42 day head-down bed rest (day 22 and 42) but also before and 6 days after head-down bed rest (-6 degrees). Coarse graining spectral analysis was used to extract the non-harmonic (fractal) component from each time series. The power spectral densities of this fractal component are inversely proportional to their frequency (1/f beta). We fitted an inverse power law estimate to the fractal component to determine the spectral exponent beta. The complex dynamics of blood pressure and heart rate variability were also analyzed by correlation dimension and non-linear prediction. Bed rest induced orthostatic intolerance in 4 subjects. There was a significant increase in the spectral exponent beta of RR-interval variability during and after head-down bed rest (before: 1.039 +/- 0.090; during: 1.552 +/- 0.080 and 1.547 +/- 0.100; after: 1.428 +/- 0.040). Analysis of the blood pressure dynamics indicated lower correlation dimensions during head-down bed rest and higher coefficients of predictability after head-down bed rest. Complexity alterations of RR-interval and blood pressure variability were not linked with one another during head-down bed rest. These alterations seemed to be correlated with the orthostatic intolerance observed after bed rest. These results suggest a change of the integration level of cardiovascular autonomic regulation.

No effect of venoconstrictive thigh cuffs on orthostatic hypotension induced by head-down bed rest.

Orthostatic intolerance (OI) is the most serious symptom of cardiovascular deconditioning induced by head-down bed rest or weightlessness. Wearing venoconstrictive thigh cuffs is an empirical countermeasure used by Russian cosmonauts to limit the shift of fluid from the lower part of the body to the cardio-cephalic region. Our aim was to determine whether or not thigh cuffs help to prevent orthostatic hypotension induced by head-down bed rest. We studied the effect of thigh cuffs on eight healthy men. The cuffs were worn during the day for 7 days of head-down bed rest. We measured: orthostatic tolerance (stand tests and lower body negative pressure tests), plasma volume (Evans blue dilution), autonomic influences (plasma noradrenaline) and baroreflex sensitivity (spontaneous baroreflex slope). Thigh cuffs limited the loss of plasma volume (thigh cuffs: -201 +/- 37 mL vs. control: -345 +/- 42 mL, P < 0.05), the degree of tachycardia and reduction in the spontaneous baroreflex sensitivity induced by head-down bed rest. However, the impact of thigh cuffs was not sufficient to prevent OI (thigh cuffs: 7.0 min of standing time vs. control: 7.1 min). Decrease in absolute plasma volume and in baroreflex sensitivity are known to be important factors in the aetiology of OI induced by head-down bed rest. However, dealing with these factors, using thigh cuffs for example, is not sufficient to prevent OI. Other factors such as venous compliance, microcirculatory changes, peripheral arterial vasoconstriction and vestibular afferents must also be considered.

Orthostatic tolerance and hormonal changes in women during 120 days of head-down bed rest.

BACKGROUND: Women will be included as mission specialists in the upcoming International Space Station program. This paper describes the changes in volume-regulating hormones and determines the degree of degradation in orthostatic tolerance in a group of women after 120 d of bed rest. The aim of this study was to test a countermeasure program to be used by women during long-duration spaceflights. METHODS: For 120 d of -6 degrees head-down bed rest (HDBR), eight healthy women were assigned either to a no-countermeasure (No-CM, n = 4), or to a countermeasure (CM, n = 4) group. In the countermeasure group, exercise began after 2 wk, pharmacological agents were given during the 1st and 3rd mo, and the "Centaur" suit was worn on the last day of bed rest and during the day time for several days after bed rest. Diet supplements were taken during the 1st and 4th mo of HDBR. Tilt tests were run before and after HDBR. RESULTS: After the HDBR, none of the CM subjects, had pre-syncopal or syncopal symptoms during tilt tests: BP was well maintained in the CM group, while heart rate and BP changed in the No-CM group. In plasma, atrial natriuretic peptide (ANP) increased in both groups and remained high throughout HDBR, while aldosterone increased and remained elevated in the No-CM group. Natriuresis was decreased during HDBR. CONCLUSION: The CM protocols used during this study were efficient and prevented orthostatic intolerance for the four CM subjects. It would be necessary to obtain more data regarding this set of CM protocols on female subjects to lead to statistical and formal conclusions.

Characterisation of gravity-induced facial skin oedema using biophysical measurement techniques.

BACKGROUND/AIMS: In humans, the microgravity environment can be expected to induce swelling of facial tissues and shrinking of the tissues in the lower limbs, together with a loss in body weight. To evaluate fluid shifts in skin, the head-down bed-rest model was used. The aim of the present study was to evaluate the appearance of facial oedema in subjects undergoing anti-orthostatic bed-rest at an angle of -10 degrees. METHODS: The forehead of each of four subjects was measured before and after 1, 10 and 24 h in this head-down tilt position. At these time points, interstitial fluid migration and facial oedema were assessed using a high resolution B-scan ultrasound and a device for measuring the skin's mechanical properties. RESULTS: The results obtained showed a progressive increase in dermal thickness and initial stress, and a reduction in stiffness and elasticity of the skin during the study period. CONCLUSIONS: This preliminary study has demonstrated the feasibility of the method in measuring fluid displacement and retention in the skin. Furthermore, it highlights the influence of fluids on the mechanical behaviour of the skin. These techniques could be used for studying the redistribution of liquid masses during periods spent in space.

Observations in energy and macronutrient intake during prolonged bed-rest in a head-down tilt position.

OBJECTIVE: to report observations in energy and macronutrient intakes, and body weight during prolonged bed-rest in a head down tilt (HDT) position. DESIGN: open study, each subject was his own control, and was studied during 14 days of baseline, 42 days of -6 degrees HDT bed-rest, and 12 days of recovery. SUBJECTS: eight healthy young man were recruited, one dropped out. METHODS: energy and macronutrient content of the diet were calculated from weighed amounts of food consumed and French food composition tables. RESULTS: body weight declined during HDT (74.0+/-3.2 to 71.8+/-3.2 kg, P<< 0.001) and increased during recovery (72.7+/-3.2 kg, P<< 0. 001). Energy intake decreased during HDT (by 17% after 4-5 weeks) and increased during recovery but remained lower than during baseline (P<< 0.001). During HDT fat intake, expressed by a percentage of energy, decreased (P<< 0.01) while carbohydrate increased (P= 0.04); protein intake did not change (P= 0.08). The reverse trends were observed during recovery. CONCLUSIONS: the present study reports a spontaneous reduction in energy and relative fat intake during prolonged HDT bed rest. We believe that these findings have implications for the clinical setting.

Effects of a three-day head-down tilt on renal and hormonal responses to acute volume expansion.

To clarify whether exposure to 6 degrees head-down tilt (HDT) leads to alterations in body fluid volumes and responses to a saline load similar to those observed during space flight we investigated eight healthy subjects during a 4-day, 6 degrees HDT and during a time-control ambulatory period with cross-over. Compared with the ambulatory period, HDT was associated with greater urinary excretion of water and sodium (UV, U(Na)V) from 0 to 12 h (cumulated UV 1,781 +/- 154 vs. 1,383 +/- 170 ml, P < 0.05; cumulated U(Na)V 156 +/- 14 vs. 117 +/- 9 mmol, P < 0.05), and with higher plasma atrial natriuretic factor (ANF) at 4 h. Hemoglobin and hematocrit increased over the first 24 h, and blood and plasma volumes were decreased after 48 h of HDT (P < 0.05). Plasma renin activity (PRA) and aldosterone did not differ between the two groups. With prolongation of HDT, UV and U(Na)V returned close to baseline values. On the fourth HDT day, a 30-min infusion of 20 ml/kg isotonic saline was performed, while a large oral water load maintained a high urine output. The ambulatory period experiment was done with the subjects in the acute supine posture. Sodium excreted within 4 h of loading was 123 +/- 8 mmol during HDT vs. 168 +/- 16 mmol during the ambulatory period (P < 0.05). The increase in plasma ANF and decrease in PRA were greater during HDT than during the ambulatory period (ANF 30 +/- 5 vs. 13 +/- 4 pg/ml, P < 0.05; PRA -1.4 +/- 0.4 vs. -0.5 +/- 0.2 ng. ml(-1). h(-1), P < 0.05). Our data suggest that after a 3-day HDT period, thoracic volume receptor loading returns to the level seen in the upright position, leading to blunted responses to volume expansion, compared with acute supine control.

Hormonal changes during a 20-week confinement.

BACKGROUND: When the European Space Agency planned the EUROMIR'95 long-duration flight with a European astronaut on board the Russian orbital MIR station, it organized simultaneously a ground simulation, called the Human Behaviour Study, of this manned space mission. The ground simulation was a confinement experiment, and this paper describes the changes in volume-regulating hormones that occurred during and after 20 weeks of confinement. METHODS: In a normobaric diving chamber, 3 subjects were confined for 135 d. Arterial pressure, plasma concentrations of blood volume-regulating hormones (active renin and arginine-vasopressin), and urinary variables (aldosterone, arginine-vasopressin, and metabolites of catecholamines) were measured before, during, and after confinement. RESULTS: Arterial pressure was increased from week 1 until week 15 of confinement, while heart rate was elevated from week 6 until the end of the simulation. Plasma active renin was elevated throughout the confinement (after week 6). Urine volume increased transitively on the first 2 d of confinement. CONCLUSIONS: The results obtained during this long-term confinement experiment have major importance regarding concerns about spaceflight and bed rest data, because we observed hormonal changes during the experiment that normally are assigned to the fluid shift that occurs in weightlessness or in the head-down tilt position (i.e., an increase of renin, an increase of urinary volume during the first two days, and a decreased urinary cyclic guanosine monophosphate.

Changes in the sympathetic nervous system induced by 42 days of head-down bed rest.

Changes in autonomic nervous system activity could be linked to the orthostatic intolerance (OI) that individuals suffer after a spaceflight or head-down bed rest (HDBR). We examined this possibility by assessing the sympathetic nervous system activity during 42 days of HDBR in seven healthy men. Heart rate variability was studied with the use of power spectral analysis, which provided indicators of the sympathetic (SNSi) and parasympathetic (PNSi) nervous system influences on the heart. Urinary catecholamines and the spontaneous baroreflex sensitivity were measured. Urinary catecholamines decreased by 21.3%, showing a decrease in SNSi. Heart rate variability was greatly reduced during 42 days of HDBR with a drop in PNSi but with no significant changes in SNSi. The baroreflex sensitivity was greatly reduced (30.7%) on day 42 of HDBR. These results suggest a dissociation between the catecholamine response and the SNSi of the heart rate. This dissociation could be the consequence of an increase in beta-adrenergic receptor density and/or activity induced by a decrease in catecholamines during HDBR. The subjects who suffered from OI also had a greater sympathetic response and much lower baroreflex sensitivity when supine than those who finished the stand test. However, the mean response of all subjects indicated that the sympathetic activity (catecholamine excretion) was probably slightly inhibited during HDBR and could contribute to OI.

Cardiovascular responses to orthostatic tests after a 42-day head-down bed-rest.

Cardiovascular responses to orthostatic tests were studied before and after a prolonged 42 day-head-down bed-rest (HDBR;-6 degrees) experiment simulating a long duration space flight. Seven men participating in the experiment underwent stand tests (10 min) and lower body negative pressure (LBNP) tests (5 min at -25, -35, -45 mmHg). Heart rate variability and spontaneous baroreflex response slope (SBS) were analysed to assess autonomic nervous system responses. Changes in plasma volume (PV) were assessed at the end of HDBR. At the end of HDBR, four subjects could not complete the stand tests and one could not complete the LBNP test. A higher stressed heart rate with standing (+ 44% before and + 57% after HDBR) and LBNP exposure (+ 19% before and + 34% after HDBR) were observed. A decrease in blood pressure (BP) reflecting a reduced vasomotor response was only observed with standing (mean BP + 21% before and -8% after HDBR); LBNP was less sensitive probably because it was performed 6 h after the stand test. The PV decreased by 10.6%. A decline in spectrum total power reflecting a reduced variance of RR-interval, a decrease in parasympathetic activity and an increase in sympathetic one were observed at the end of HDBR. The reduced parasympathetic indicator and SBS would suggest that the vagal nerve component of the cardiovascular control had been diminished. Except for a lower BP when standing after HDBR, no significant difference was observed between finishers and non-finishers. Autonomic nervous system changes including reduced vasomotor responses constituted important contributors to the orthostatic intolerance observed here and after space flights. Some autonomic and PV changes seemed to be opposite to those observed with training and would suggest a role of reduced physical activity in cardiovascular changes induced by HDBR.