Pain and Vertebral Dysfunction in Dry Immersion: A Model of Microgravity Simulation Different from Bed Rest Studies.

BACKGROUND: Astronauts frequently experience back pain during and after spaceflight. The aim of this study was to utilize clinical methods to identify potential vertebral somatic dysfunction (VD) in subjects exposed to dry immersion (DI), a model of microgravity simulation. METHOD: The experiment was performed in a space research clinic, respecting all the ethical rules, with subjects completing three days of dry immersion (n = 11). Assessments of VD, spine height, and back pain were made before and after simulated microgravity. RESULTS: Back pain was present in DI with great global discomfort during the entire protocol. A low positive correlation was found (Pearson r = 0.44; P < 0.001) between VD before DI and pain developed in the DI experiment. CONCLUSIONS: There is a specific location of pain in both models of simulation. Our analysis leads to relativizing constraints on musculoskeletal system in function of simulation models. This study was the first to examine manual palpation of the spine in a space experience. Additionally, osteopathic view may be used to select those individuals who have less risk of developing back pain.

Involvement of nitric oxide in corticosterone release and glucose metabolism in food deprived rats.

This study was performed to investigate the involvement of nitric oxide (NO) in corticosterone, endpoint product of hypothalamo-pituitary-adrenal (HPA) axis activation, and metabolic responses to 3 days of food deprivation. To investigate this aim, we used a nonspecific inhibitor of nitric oxide synthases, N-nitro- L-arginine methyl ester (L-NAME). In food deprived group we have noted a significant increase in plasma corticosterone concentration accompanied by a significant depletion in hepatic glycogen content with concomitant increase in glycogen phosphorylase (GP) activity by 63.72%, key enzyme of glycogenolysis and decrease in hexokinase (HK) activity by 25.16%, leading to significant decrease in glucose concentration. However, L-NAME administration in food deprived rats decreased slightly corticosterone level and GP activity (16.39%) and increased HK activity (11.26%) as compared to food deprived group. Considering these results, we can deduce that in food deprivation nitric oxide is involved in the regulation of corticosterone release and in glucose metabolic responses via glycogenolysis activation by the stimulation of GP activity and the inhibition of HK activity. However, more studies are necessary to further clarify the mechanisms by which NO induces these responses.

Assessing erectile neurogenic dysfunction from heart rate variability through a Generalized Linear Mixed Model framework.

BACKGROUND: The low (LF) vs. high (HF) frequency energy ratio, computed from the spectral decomposition of heart beat intervals, has become a major tool in cardiac autonomic system control and sympatho-vagal balance studies. The (statistical) distributions of response variables designed from ratios of two quantities, such as the LF/HF ratio, are likely to non-normal, hence preventing e.g., from a relevant use of the t-test. Even using a non-parametric formulation, the solution may be not appropriate as the test statistics do not account for correlation and heteroskedasticity, such as those that can be observed when several measures are taken from the same patient. OBJECTIVES: The analyses for such type of data require the application of statistical models which do not assume a priori independence. In this spirit, the present contribution proposes the use of the Generalized Linear Mixed Models (GLMMs) framework to assess differences between groups of measures performed over classes of patients. METHODS: Statistical linear mixed models allow the inclusion of at least one random effect, besides the error term, which induces correlation between observations from the same subject. Moreover, by using GLMM, practitioners could assume any probability distribution, within the exponential family, for the data, and naturally model heteroskedasticity. Here, the sympatho-vagal balance expressed as LF/HF ratio of patients suffering neurogenic erectile dysfunction under three different body positions was analyzed in a case-control protocol by means of a GLMM under gamma and Gaussian distributed responses assumptions. RESULTS: The gamma GLMM model was compared with the normal linear mixed model (LMM) approach conducted using raw and log transformed data. Both raw GLMM gamma and log transformed LMM allow better inference for factor effects, including correlations between observations from the same patient under different body position compared to the raw LMM. The gamma GLMM provides a more natural distribution assumption of a response expressed as a ratio. CONCLUSIONS: A gamma distribution assumption intrinsically models quadratic relationships between the expected value and the variance of the data avoiding prior data transformation. SAS and R source code are available on request.

Cardiovascular deconditioning: From autonomic nervous system to microvascular dysfunctions.

Weightlessness induces an acute syndrome called the cardiovascular deconditioning, associating orthostatic intolerance with syncope, increase in resting heart rate and decrease in physical capability. Orthostatic intolerance occurs after short term and long term head down bed rest and after long term space flight. Both head down bed rest and space flight induce a significant decrease of the spontaneous baroreflex sensitivity. However, spontaneous baroreflex sensitivity only characterizes the cardiac baroreflex loop. To go further with the analysis of cardiovascular deconditioning we were interested in the microcirculation. As the endothelium plays a crucial role in the regulation of vascular homeostasis and local blood flow, we hypothesized that endothelial dysfunction is associated with bed rest induced changes. We investigated endothelial properties before and after 56 days of bed rest in 8 women of control group and in 8 women who regularly performed physical exercise as countermeasure. Our study shows that prolonged bed rest causes impairment of endothelium-dependent functions at the microcirculation level, along with an increase in circulating endothelial cells. Endothelium should be a target for countermeasures during periods of prolonged bed rest or exposure to weightlessness.

Intracerebroventricular capsaicin influences the body weight increasing of rats.

Adult rats were treated for ten days with capsaicin or with NaCl 0.9% directly injected into the lateral cerebral ventricles through a surgically implanted cannula. A third group of rats was implanted with the same cannula but did not receive any treatment. The food intake and the body weight were recorded for at least six weeks after stopping the treatment. The animals were always kept at constant ambient temperature of 22 °C. The body weight of the capsaicin-treated group was reduced by the treatment, and showed a regular but lower degree of recovery trend than the control groups after the treatment period. In fact the capsaicin treated animals never reached the body weight of the controls. Nevertheless, food intake did not significantly vary after the capsaicin treatment. On the basis of these and previous findings, we can assume that capsaicin injected into the cerebral ventricles to rats kept at constant ambient temperature can acts on hypothalamic neurons, but a permanent action on metabolic pathways can not be excluded.

[Uterine electromyogram: principle and interest in the diagnosis of preterm labour]. / L'électromyogramme utérin: principes et intérêt pour le diagnostic de travail prématuré.

Preterm labour diagnosis rely on clinical arguments exhibiting low positive predictive values. Discrimination between uterine contractions leading to preterm delivery and physiologic uterine activity increase throughout pregnancy and remains difficult. Uterine electrical activity can be recorded non-invasively from the abdominal wall and could help in the diagnosis of preterm labour. Electrical signal characteristics are reflecting myometrial cells electrical properties which are varying throughout pregnancy and labour. During pregnancy, uterine electrical activity is very low. During term and preterm labour, uterine electrical activity increases as well as mechanical activity. Bursts become regular with high amplitude. Spectral analysis demonstrates an increase in the frequency content, as represented by the shift of the burst power density spectrum peak frequency from low to high frequencies. Consequently, the electromyogram signal reflects myometrial excitability and allows differentiating powerful uterine contractions leading to delivery from uterine physiologic activity. Moreover, electromyogram signal modifications occur before any increase in mechanical activity in the pregnant rats, allowing identification of preterm labour earlier than uterine mechanical activity measured by intrauterine pressure. Two studies performed in women present with preterm contractions are supporting the potential interest of the uterine electromyogram recording to help in the diagnosis of preterm labour; but further investigations are necessary.

Vasopressin and nitric oxide synthesis after three days of water or food deprivation.

Nitric oxide has been suggested to be involved in the regulation of fluid and nutrient homeostasis. In the present investigation, vasopressin and nitric oxide metabolite (nitrite and nitrate) levels were determined in plasma of male Wistar rats submitted to water or food deprivation for three days. Hematocrit and plasma sodium showed marked increase in dehydrated and starved rats. Potassium levels and plasma volume decreased in both treated groups. Plasma osmolality and vasopressin levels were significantly elevated in water deprived (362.8 +/- 7.1 mOsm/kg H2O, 17.3 +/- 2.7 pg/ml, respectively, p < 0.001) rats, but not in food deprived (339.9 +/- 5.0, 1.34 +/- 0.28) rats, compared to the controls (326.1 +/- 4.1, 1.47 +/- 0.32). The alterations observed in plasma vasopressin levels were related to plasma osmolality rather than plasma volume. Plasma levels of nitrite and nitrate were markedly increased in both water and food deprived rats (respectively, 2.19 +/- 0.29 mg/l and 2.22 +/- 0.17 mg/l versus 1.33 +/- 0.19 mg/l, both p < 0.01). There was a significant negative correlation between plasma nitrite and nitrate concentration and plasma volume. These results suggest that both dehydration and starvation increase plasma nitric oxide, probably by activation of nitric oxide synthases. The release of nitric oxide may participate in the regulation of the alteration in blood flow, fluid and nutrient metabolism caused by water deprivation or starvation.

Rats desensitized by capsaicin alter their food intake regulation especially at cold ambient temperature.

Adult rats were treated subcutaneously for 10 days with capsaicin, and their food intake and body weight were recorded for almost 6 weeks after stopping the treatment. The animals were exposed to different ambient temperatures: Ta (22, 32, 35, 10 and 22 degrees C). In the capsaicin-treated group a persistent increase in food intake and a reduction of body weight were observed when the animals were exposed to the lowest Ta of 10 degrees C. Starting from this temperature, food intake remained significantly higher than in controls until the end of the experiment at a Ta of 22 degrees C. The discrepancy between body weight increase and food intake especially at low temperature (10 degrees C) suggests that capsaicin could prevent suppression of food intake through the mediation of capsaicin-sensitive vagal afferent fibers by activation of cold-temperature-sensitive receptors.

Assessment of cardiovascular autonomic control by the empirical mode decomposition.

OBJECTIVES: Heart-rate variability (HRV) is an interesting tool for assessing cardiac autonomic system control, but nonstationarities raise problematic issues. The objective of this paper is to show that adapted signal processing tools may cope with nonstationary situations and improve the analysis of HRV. METHODS: We propose to use the recent method of Empirical Mode Decomposition (EMD), so as to analyze the cardiac sympatho-vagal balance on automatically extracted modes. The method, which is fully data-adaptive, consists in an iterative decomposition based on the idea that any signal can be locally represented as an oscillation superimposed to a more regular trend. When a signal is composed of distinct nonstationary components, EMD therefore achieves a time-varying filtering which effectively separates them. RESULTS: The method has been applied to situations where postural changes occur, provoking instantaneous changes in heart rate as a result of autonomic modifications. In the considered application where the sympatho-vagal balance is quantified by comparing the low-frequency (LF) and high-frequency (HF) components of RR intervals, EMD automatically achieves a separation of these components upon which further processing can be carried. Visualizing the decomposition in the time-frequency plane, we can identify local events due to the postural changes, and we can assess a (time-varying) HF vs. LF discrimination without resorting to some fixed high-pass/low-pass filtering. CONCLUSION: Assessing cardiovascular autonomic control by resorting to LF/HF measurements may prove difficult in nonstationary situations where the use of a priori fixed filters can be questioned. Because it is both local and fully data-adaptive, EMD appears as an appealing and versatile pre-processing technique for overcoming some of the limitations that conventional spectral methods are faced with in nonstationary situations.

Hormonal changes during long-term isolation.

Confinement and inactivity induce considerable psychological and physiological modifications through social and sensory deprivation. The aim of the SFINCSS-99 experiment was to determine the cardiovascular and hormonal pattern of blood volume regulation during long-term isolation and confinement. Simulation experiments were performed in pressurized chambers similar in size to the volumes of modern space vehicles. Group I consisted of four Russian male volunteers, who spent 240 days in a 100-m(3 )chamber. Group II included four males (one German and three Russians) who spent 110 days in isolation (200-m(3) module). The blood samples, taken before, during and after the isolation period, were used to determine haematocrit (Ht), growth hormone (GH), active renin, aldosterone, and osmolality levels. From the urine samples, electrolytes, osmolality, nitrites, nitrates, cortisol, antidiuretic hormone (ADH), aldosterone, normetanephrine and metanephrine levels were determined. The increase in plasma volume (PV) that is associated with a tendency for a decrease in plasma active renin is likely to be due to decreased sympathetic activity, and concords with the changes in urinary catecholamine levels during confinement. Urinary catecholamine levels were significantly higher during the recovery period than during confinement. This suggests that the sympathoadrenal system was activated, and concords with the increase in heart rate. Vascular resistance is determined by not only the vasoconstrictor but also vasodilator systems. The ratio of nitrite/nitrate in urine, as an indicator of nitric oxide release, did not reveal any significant changes. Analysis of data suggests that the duration of the isolation was a main factor involved in the regulation of hormones.

Vasopressin and galanin expression in the hypothalamus of two African rodents, Taterillus gracilis and Steatomys caurinus, subjected to water-restriction.

The expression of arginine-vasopressin (AVP) and galanin (GAL) was studied by immunohistochemistry and in situ hybridization in the hypothalamus of two species of African rodents. In the wild, these animals experience successive arid and wet seasons that alternately stimulate their antidiuretic and diuretic systems. In this study, animals were subjected to both standardized laboratory conditions and to eight days of water-restriction. Under both sets of conditions, AVP and GAL were detected in the supraoptic nucleus (SON), paraventricular nucleus (PVN), and median eminence (ME). AVP and GAL responses to water-restriction differed in the two species, as did behavioral adaptations to the hot-dry season. In Taterillus gracilis, AVP- and GAL-LI (like immunoreactivity) peptide and mRNA levels increased in the SON. AVP-LI peptide and mRNA levels increased in the PVN, whereas only AVP-LI peptide levels increased in the ME. Pituitary gland AVP pools were unchanged by water deprivation, whereas urinary AVP levels and osmolality increased. The AVP response is typical of that of desert rodents, favoring survival under conditions of water-restriction. In Steatomys caurinus, which estivates, AVP and GAL-LI peptide levels decreased in the hypothalamus, as they did in the laboratory rat. In the SON, AVP, and GAL mRNA levels increased, whereas, in the PVN, only AVP mRNA levels increased. Pituitary gland AVP levels decreased, whereas urinary AVP levels and osmolality increased. In both species, the changes in the amount of GAL-LI peptide appeared to be closely linked to changes in AVP levels, suggesting that this peptide is involved in the osmoregulatory response to water-restriction.

Influence of hypergravity on hypothalamic vasopressin and oxytocin neurons in rats.

This study was aimed to evaluate the reaction of the vasopressin (VP) and oxytocin (OT) neurons of the supraoptic nucleus (SON) in rats to single or repeated hypergravity (HG). Special attention was paid to the tyrosine hydroxylase (TH) expression in VP neurons as a marker of the neuron activation. Rats were revolved in a centrifuge with overloading 2G for 5 days or 34 days as well as for 34 days plus 5 days with an interval of 39 days between two rotations. Control rats were kept in a centrifuge room. Radioimmununoassay, quantitative and semi-quantitative immunocytochemistry and in situ hybridization were used to evaluate: a) VP concentration in the pituitary posterior lobe (PL) and in plasma; b) the number of VP-, OT- and TH-immunoreactive neurons in the SON; c) the optic density of VP-, OT- and TH-immunoreactive materials in cell bodies (SON) and distal axons (PL), d) the optic density of VP and OT mRNAs signals (S35) in the whole SON on microfilms. According to our data, VP neurons were strongly activated during HG (5 days or 34 days) that was manifested in the functional hypertrophy of the neurons, greatly increased concentrations of VP mRNA in the SON and VP in plasma, the onset of the TH expression. The neurons showed initially (5 days) the functional insufficiency (VP release > VP synthesis) followed by their adaptation (subsequent 29 days) to the increased need in VP (VP release < VP synthesis). No reaction of VP neurons was observed to repeated HG. In contrast to VP neurons, OT neurons did not react to short-term HG or showed functional depression after the long-term treatment.

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.

Comparison of passive heat or exercise-induced dehydration on renal water and electrolyte excretion: the hormonal involvement.

The effects of hydromineral hormones and catecholamines on renal water and electrolyte excretion were examined during and after dehydration induced by either passive heat or exercise. Eight healthy young Caucasian subjects participated in three separate trials, each including three consecutive phases. Phases 1 and 3 involved a 90-min period at rest in a thermoneutral environment, while phase 2 involved a 120-min period designed to provide: (1) euhydration (control trial), (2) passive heat-induced dehydration of 2.8% body mass, or (3) exercise-induced dehydration of 2.8% body mass. During the two dehydration procedures, the decreases in urine flow and sodium excretion were more marked during exercise (P < 0.05). An increase in plasma catecholamines occurred only during exercise, together with a reduction in creatinine clearance and more marked increases in plasma renin and aldosterone than during passive heat exposure (P < 0.05). Although plasma vasopressin was elevated during the two dehydration procedures, urine osmolality did not change and, moreover, free water clearance increased during exercise (P < 0.05). Plasma levels of atrial natriuretic peptide increased markedly only during exercise compared to the other trials (P < 0.05). After the dehydration procedures, urine flow decreased again and urine osmolality increased markedly (P < 0.05), while plasma vasopressin remained elevated. These results suggest that sympathoadrenal activation during exercise plays a major role in the more marked reduction in diuresis and natriuresis than during passive heat exposure. Despite high plasma vasopressin concentrations during the two dehydrating events, the observed antidiuresis was not due to an increased renal concentrating ability, and the vasopressin was more effective after the dehydration procedures.

Influence of head-down bed rest on the circadian rhythms of hormones and electrolytes involved in hydroelectrolytic regulation.

We investigated in six men the impact of a 17-day head-down bed rest (HDBR) on the circadian rhythms of the hormones and electrolytes involved in hydroelectrolytic regulation. This HDBR study was designed to mimic an actual spaceflight. Urine samples were collected at each voiding before, during and after HDBR. Urinary excretion of aldosterone, arginine vasopressin (AVP), cyclic guanosine monophosphate (cGMP), cortisol, electrolytes (Na+ and K+) and creatinine were determined. HDBR resulted in a significant reduction of body mass (P < 0.01) and of caloric intake [mean (SEM) 2,778 (37) kcal.24 h(-1) to 2,450 (36) kcal.24 h(-1), where 1 kcal.h(-1) = 1.163 J.s(-1); P< 0.01]. There was a significant increase in diastolic blood pressure [71.8 (0.7) mmHg vs 75.6 (0.91) mmHg], with no significant changes in either systolic blood pressure or heart rate. The nocturnal hormonal decrease of aldosterone was clearly evident only before and after HDBR, but the day/night difference did not appear during HDBR. The rhythm of K+ excretion was unchanged during HDBR, whereas for Na+ excretion, a large decrease was shown during the night as compared to the day. The circadian rhythm of cortisol persisted. These data suggest that exposure to a 17-day HDBR could induce an exaggeration of the amplitude of the Na+ rhythm and abolition of the aldosterone rhythm.

Smoothed pseudo Wigner-Ville distribution as an alternative to Fourier transform in rats.

Techniques for examining signals in the time and frequency domains are well-established tools. These tools have their limitations; they tell us in a broad sense where the signal component exists in the frequency domain, but they do not tell us how its frequency characteristics change over time. The time-frequency has become a powerful alternative for the analysis of signals. Among various time-frequency distribution methods, one of the most studied is the Wigner-Ville distribution. The aim of this study was to evaluate in conscious rats smoothed pseudo Wigner--Ville distribution (SPWVD) as an alternative to the fast Fourier transform (FFT) in RR intervals and in systolic blood pressure (SBP), before and after adrenergic and cholinergic receptor blockade. Fourteen Wistar rats equipped with telemetry probe were evaluated: (1) under control conditions; (2) after injection of saline (100 microl kg(-1) i.v.); (3) after atenolol (1 mg kg(-1) i.v.); (4) after atropine methyl nitrate (0.5 mg kg(-1) i.v.); and (5) after phentolamine (5 mg kg(-1) i.v.). FFT and SPWVD were applied to RR intervals and SBP time series. Six-minute time series of RR intervals, systolic and diastolic pressures were analysed. The bias and distribution of differences between FFT and SPWVD methods in RR intervals under base conditions were 1.4+/-0.4% (r2=0.94; P<0.01) in LF/LF+HF: 1.5+/-0.5% ( r2=0.92; P<0.01) in HF/LF+HF and 4.8+/-1.9% (r2=0.92; P<0.01) in LF/HF. In SBP the bias and distribution were 1.5+/-0.8% (r2=0.90) P<0.05) in LF/LF+HF and 1.7+/-0.6% (r2=-0.92; P<0.01) in HF/LF+HF. In the frequency domain analysis of RR intervals and SBP there was no difference between FFT and SPWVD. The agreement between the methods demonstrates that in stationary signals both methods can be used interchangeably. SPWVD may be an interesting tool to analyse biomedical signals; it provides a good resolution at high frequency and a good frequency resolution at low frequencies independently if signals remain stationary.

Hyperalgesic effect of intrathecally administered interleukin-1 in rats.

The present study demonstrates that intrathecal injection of interleukin-1 (IL-1) in rats at a dose of 50 pg or 500 pg induced a significant hyperalgesic effect in the hot-plate test. The hyperalgesia or the altered nociceptive responses were not considered to be the result of sensitization to the hot plate, since the nociceptive alteration caused by intrathecal administration of IL-1 stopped after 20 min. The results suggest that IL-1 can affect pain responsiveness in a dose-dependent manner and that it is able to modulate neuronal functions. Taken together, our findings and the data from the literature suggest that IL-1-induced hyperalgesia is related not only to the route of administration but also to the algesia testing method used.

Intracerebroventricular capsaicin and food intake in the rat.

To investigate whether capsaicin affected food intake and body weight and/or interfered with the mechanisms regulating the body temperature, capsaicin was administered intracerebroventricularly to rats at a daily dose of 25 micrograms of 5 microliters of vehicle for 10 consecutive days. The vehicle consisted of 5% ethanol plus 5% Tween 80 in isotonic saline. The ambient temperature (Ta) was 22 degrees C. Two control groups were used: the first group was treated with the vehicle but its concentration was lowered 10 times in order to avoid the wellknown brain toxicity of Tween 80; the second group was injected with NaCl 0.9% alone. The subsequent observation period lasted 38 days and the rats were exposed to a Ta of 22, 32, 35, 10 and 22 degrees C for different times. Food intake and body weight showed a remarkable decrease during the treatment period in both the capsaicin- and vehicle-treated groups. During the observation period, food intake behavior and body weight evolution were different among the three groups of treated rats. The influence of Ta was most apparent in the capsaicin-treated rats that showed a long-lasting deficit in their body weight and a clear inability to regulate their body temperature (Tb) in a warm environment (Ta 35 degrees C). However, the capsaicin-treated rats began to recover from the weight loss when they were finally housed at Ta 22 degrees C. Tween 80-treated rats began to recover from the weight loss earlier, the pretreatment body weight having been reached during Ta 32 degrees C exposure, i.e., 12 days after the end of the treatment. Since capsaicin did not reduce food intake for a long time during the recovery process, the effect of capsaicin on Ta and body weight seems to be related to metabolic processes. Under the conditions of the present study, neither capsaicin nor Tween 80 seem to have permanently impaired the animals' energy balance regulation.

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.