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.

[SHIFTS IN URINE PROTEIN PROFILE DURING DRY IMMERSION].

The study was aimed at tracking the proteomic profile of urine in 8 normal volunteers to 5-day dry immersion (DI). The proteome composition was determined by chromatography-mass spectrometry on high-efficient on-line liquid nano chromatograph Agilent 1100; complementary information about the protein spectra was obtained by dint of mass-spectrometer MaXis Impact 4G and hybrid mass-spectrometer LTQ-FT. Functional associations between proteins and biological functions were analyzed using computer system ANDCell (Associative Networks Discovery in Cells). A total of 256 proteins were identified; for 43 proteins difference in the detection rate during the baseline data collection and on DI day 4 exceeded 20%.

The cardiovascular effects of salidroside in the Goto-Kakizaki diabetic rat model.

Many factors, including hyperglycemia, hypertension, obesity, dyslipidemia, and a sedentary lifestyle, contribute to a high prevalence of cardiovascular disease. Specific vascular impairment treatments in the context of diabetes and vascular risk need to be improved. Salidroside is the primary active component of Rhodiola rosea and has documented antioxidative, cardioprotective, and vasculoprotective properties. The aim of this study was to test the hypothesis that salidroside has protective effects against hyperglycemia, hypertension, and vasodilation impairment in the Goto-Kakizaki (GK) rat model of diabetes. We evaluated cardiovascular parameters (e.g., daytime/nighttime systolic and diastolic blood pressure, heart rate, and activity), metabolic parameters (e.g., body weight, food and water consumption, serum fructosamine level, glucose tolerance), eNOS / phospho-eNOS expression level and in vitro vascular reactivity of aorta and second-order mesenteric arteries in Wistar-Kyoto (control) and GK (diabetic) rats treated with salidroside (40 mg/kg) or placebo (water) for 5 weeks. GK rats showed hypertension, marked glucose intolerance, and impaired endothelium-dependent and endothelium-independent vasodilation capacity. Salidroside showed beneficial effects on endothelial and non-endothelial vasodilation and likely acts on the endothelium and smooth muscle cells through the soluble guanylyl cyclase pathway. Despite its vascular effects, salidroside had no effect on blood pressure and heart rate in GK and control rats, it did not improve glucose metabolism or limit hypertension in the GK model of type 2 diabetes.

[MODIFICATION OF URINE PROTEOME IN HEALTHY HUMAN DURING 21-DAY BED REST].

Mass spectromy-based proteomics was employed to analyze urine from 8 normal volunteers for a 21-day bedrest study (BR). The analysis included trypsinolysis in solution prior to liquid chromatography and tandem mass spectrometry (LC-MS/MS), and spectra processing using the bioinformatics tools. Relying on 221 IPI-indices with Score from 24 to 1700, 169 different proteins were identified. Molecular functions, biological processes and cell components as the loci of certain protein functioning were determined with the help of UniProt-GOA. Associative interactions networks were constructed using BiNGO. There were 14 proteins identified that are functional in the cardiovascular system mostly. They were annotated and -dynamics of their occurrence throughout the experiment was considered. Grounding on the biological functions of these proteins, an assumption of eligible activation of different biological processes during BR was made.

[Permanent proteins in healthy human's urine in the experiment with 520-day isolation].

Purpose of the study was to track permanent proteins of urine proteome in the 520-day isolation experiment at the IBMP Ground-Based Test Facility with controlled environmental parameters. Object of the investigation was urine sampled from 6 normal male subjects at the age of 25 to 37 years. Second morning aliquots were gathered during baseline data collection, on days 50, 93, 124, 153, 180, 251, 274, 303, 330, 371, 400 and 427 of isolation, and in 7 days after its completion. Samples were subject to chromatography-mass spectrometry; results were analyzed with the help of bioinformatics resources. The following 7 permanent proteins were observed in urine over the entire length of the investigation: epidermal growth factor, polymer immunoglobulin receptor, plasma serine protease inhibitor, protein AMBP, keratin, type II cytoskeletal 1, collagen alpha-1 (vi) chain, serum albumin.

WISE 2005: responses of women to sublingual nitroglycerin before and after 56 days of 6° head-down bed rest.

This study tested the hypothesis that cardiovascular effects of sublingual nitroglycerin (NG) would be exaggerated after 56 days of 6° head-down bed rest (HDBR) in women, and that an aerobic and resistive exercise countermeasure (EX, n = 8) would reduce the effect compared with HDBR without exercise (CON, n = 7). Middle cerebral artery maximal blood flow velocity (CBFV), cardiac stroke volume (SV), and superficial femoral artery blood flow (Doppler ultrasound) were recorded at baseline rest and for 5 min following 0.3 mg sublingual NG. Post-HDBR, NG caused greater increases in heart rate (HR) in CON compared with EX (+24.9 ± 7.7 and +18.8 ± 6.6 beats/min, respectively, P < 0.0001). The increase in HR combined with reductions in SV to maintain cardiac output. Systolic, mean, and pulse pressures were reduced 5-10 mmHg by NG, but total peripheral resistance was only slightly reduced at 3 min after NG. Reductions in CBFV of -12.5 ± 3.8 cm/s were seen after NG, but a reduction in the Doppler resistance index suggested dilation of the middle cerebral artery with no differences after HDBR. The femoral artery dilated with NG and blood flow was reduced ∼50% with the appearance of large negative waves suggesting a marked increase in downstream resistance, but there were no effects of HDBR. In general, responses of women to NG were not altered by HDBR; the greater increase in HR in CON but not EX was probably a consequence of cardiovascular deconditioning. These results contrast with the hypothesis and a previous investigation of men after HDBR by revealing no change in cardiovascular responses to exogenous nitric oxide.

[Seven-day dry immersion: relations between water-electrolyte and cardiovascular responses].

The paper presents the results of the experiment with 7-day dry immersion. Eight healthy men were studied before, during and after exposure. It is shown that the primary response involves hemodynamic and water-electrolyte changes. The mechanisms of cardiovascular adaptation to immersion conditions are revealed. In particular, some electrophysiological shifts in propagation of myocardial excitation are found, leading to increase in "myocardium" index, estimated by analysis of natural small oscillations in the amplitude of the PQRST complex with dispersion ECG mapping. Revealed significant reduction of functional reserves of the cardiovascular regulatory mechanisms in the process of adaptation to dry immersion is of great practical importance. The results suggest that water-electrolyte shifts induced by dry immersion are the basis and the first phase of the further changes in autonomic regulation and myocardial functional state.

[Renal functioning and human body liquids during 5-day dry immersion].

Renal function and body composition, including liquids, were investigated in 14 essentially healthy male subjects during simulation of some spaceflight effects by 5-d dry immersion (DI). Noninvasive measurement of water spaces of organism was performed with the methods of bio-impedance analysis (BIA). Increase of renal excretion of liquids and appearance of negative water balance were observed. BIA revealed reductions of total body and extracellular liquids and a decrease of circulating plasma volume. This means, that DI induced hypohydration of organism. In the post-DI period, the hydration status regained its baseline level fairly soon. Lean body mass slightly decreased; adipose mass, on the contrary, exceeded baseline values. Moreover, the experiment evidenced technical impossibility to obtain valid impedansimetry data in DI.

What are the future top priority questions in cardiovascular research and what new hardware needs to be developed?

The final discussion that took place at the Cardiovascular Workshop in Strasbourg in November 2008 identified the following priorities for our future research and the need to develop new dedicated cardiovascular devices. Knowledge and treatment of cardiovascular deconditioning remain limited. The prospect of very long duration space flights could lead to the emergence of new cardiovascular risks. We need to maintain our efforts to standardize our experimental protocols and analysis equipment. We continue to rely on animal models for cardiovascular research. To continue our studies we recommend developing specific tools for the space environment so that they can be made available to the scientific and medical community.

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.

Platelet inhibition by low-dose aspirin but not by clopidogrel reduces the axon-reflex current-induced vasodilation in humans.

We previously showed a prolonged inhibition of current-induced vasodilation (CIV) after a single oral high dose of aspirin. In this study, we tested the hypothesis of platelet involvement in CIV. Nine healthy volunteers took 75 mg aspirin/day, 98 mg of clopidogrel bisulfate/day, or placebo for 4 days. CIV was induced by two consecutive 1-min anodal current applications (0.08 mA/cm(2)) through deionized water with a 10-min interval. CIV was measured with laser Doppler flowmetry and expressed as a percentage of baseline cutaneous vascular conductance: %C(b). In a second experiment in 10 volunteers, aspirin and placebo were given as in experiment 1, but a 26-h delay from the last aspirin intake elapsed before ACh iontophoresis and postocclusive hyperemia were studied in parallel to CIV. In experiment 1, the means +/- SE amplitude of CIV was 822 +/- 314, 313 +/- 144, and 746 +/- 397%C(b) with placebo, aspirin (P < 0.05 from placebo and clopidogrel), and clopidogrel (NS from placebo), respectively. In experiment 2, CIV impairment with aspirin was confirmed: CIV amplitudes were 300 +/- 99, and 916 +/- 528%C(b) under aspirin and placebo, respectively (P < 0.05), whereas vasodilation to ACh iontophoresis (322 +/- 74 and 365 +/- 104%C(b)) and peak postocclusive hyperemia (491 +/- 137 and 661 +/- 248%C(b)) were not different between aspirin and placebo, respectively. Low-dose aspirin, even 26 h after oral administration, impairs CIV, while ACh-mediated vasodilation and postocclusive hyperemia are preserved. If platelets are involved in the neurovascular mechanism triggered by galvanic current application in humans, it is likely to occur through the cyclooxygenase but not the ADP pathway.

Metabolism in rats during antiorthostatic hypokinesia.

O2 consumption and CO2 release in 3 groups of awake rats were studied on a MM-100 metabolic monitor system (CWE Inc.). The animals of 2 groups were preadapted to 4-h maintenance in special boxes (2 weeks). The rats could perform rotational movements and limited movements in the rostrocaudal direction (hypokinesia). The animals of one group were daily exposed to 4-h antiorthostatic load (

WISE 2005: flow and nitroglycerin mediated dilation following 56 days of head down tilt bed rest with and without an exercise countermeasure.

This investigation set out to determine the effect of 56 days of head-down tilt bed rest (HDBR) and an exercise countermeasure on endothelial dependent and independent vascular function. 24women took part in this study. 8 subjects completed lower body resistance and aerobic exercise (EX, treadmill running 3-4 days per week for 40-min followed by 10-min of static LBNP, and resistive exercise on a flywheel device every 3rd day) and 16 subjects were considered as non-exercisers in a control group and a protein supplement group. FMD was induced by release of distal limb ischemia and NMD by sublingual administration of 0.3 mg of nitroglycerin before and after HDBR. Preliminary results of this study suggest that HDBR without EX results in a decreased resting diameter of the popliteal while EX increased the diameter. It is also suggested that FMD was elevated without exercise in both brachial and popliteal arteries, while pre-HDBR FMD was preserved by EX in the popliteal, but not the brachial artery. NMD appears to be elevated in the popliteal and femoral in the absence of exercise, but unchanged in the brachial artery or at any site for EX.

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.

[Clinical implications of blood pressure variability]. / Implications cliniques de la variabilité tensionnelle.

There are many variations in blood pressure, ranging from that observed between systole and diastole (pulse pressure) to slower daily or seasonal variations. This variability has many facets, for example the simple concept of variation around the mean blood pressure and the more complex spectral, chaos or fractal analysis... Some of these concepts are still the subject of fundamental research and have no current clinical applications. Others, however, are already part of our evaluation of hypertensive patients or used as prognostic factors in cardiac failure or myocardial infarction. Blood pressure variability, either the pulse pressure or 24 hour variability, is associated with a higher incidence of cardiovascular complications. Although the causality of the relationship is uncertain, patients with the greatest variability seem to be at higher risk. In addition to this prognostic impact, the study of changes in blood pressure by spectral analysis may also provide indices of adrenergic tone or sympathovagal equilibrium which may be useful clinically. Finally, the combined study of blood pressure variability and heart rate lead to the baroreflex, the sensitivity of which integrates major risk factors such as blood pressure, age, heart rate and serum cholesterol. This baroreflex could be a useful parameter for stratification of cardiovascular risk. This has already been demonstrated in patients at high risk, such as those with cardiac failure or myocardial infarction.

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.

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.

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.