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PubMed1999

Alterations in the volume stimulus-renal response relationship during exposure to simulated microgravity.

We measured central venous pressure (CVP), plasma volume (PV), urine volume rate (UVR), and circulating hormones (renin activity (PRA), vasopressin (AVP), atrial natriuretic peptide (ANP), and cortisol) before and after acute volume infusion (Dextran-40) to test the hypotheses that head-down tilt bedrest (HDT) caused (1) a resetting of the CVP operating point and (2) attenuated urine excretion. Six rhesus monkeys underwent two experimental conditions (HDT and control, each of 48 hour duration) with each condition separated by nine days of ambulatory activities to produce a cross-over counterbalance design. One test condition was continuous exposure to 10 degrees HDT and the second test condition was a control, defined as approximately 12-14 hours per day of 80 degrees head-up tilt and 10-12 hours prone. Following 48 hours of exposure to either test condition, 20-minute continuous infusion of Dextran-40 was administered. CVP in HDT was lower than the control condition. Similar elevations in CVP occurred 30 min post-infusion in both test conditions, and returned to pre-infusion baseline levels between 22 and 46 h post-infusion in both treatments. The UVR response during infusion was attenuated by HDT despite similar elevation in CVP. Elevation in ANP and reduction in PRA at the end of infusion were greater in Control compared to HDT. No differences between control and HDT were detected for AVP and cortisol responses to infusion. Since CVP returned to its pre-infusion levels following volume loading in HDT and control conditions, it appeared that the lower CVP may reflect a new operating point about which vascular volume is regulated. Further, attenuated ANP and PRA responses during vascular volume loading may contribute to depressed UVR in low gravity exposure.

Animals↗
PubMed2004

Knee extensor and plantar flexor muscle size and function following 90 days of bed rest with or without resistance exercise.

Skeletal muscle atrophy and strength loss induced by short-term simulated spaceflight are offset or attenuated by resistance exercise (RE). This study compared the effects of plantar flexor and knee extensor RE on muscle size and function in 17 healthy men (aged 26-41years) subjected to 90 days 6 degrees head-down-tilt bed rest with (BRE; n = 8) or without (BR; n = 9) RE. The RE program consisted of coupled maximal concentric and eccentric actions in the supine squat (4 sets of 7 repetitions) and calf press (4 x 14) every third day employing a gravity-independent flywheel ergometer (FW). Prior to, and following bed rest, muscle volume was assessed using magnetic resonance imaging. Similarly, muscle strength and power and surface electromyographic (EMG) activity were determined during maximal actions using FW or isokinetic dynamometry. In BR, knee extensor and plantar flexor muscle volume decreased (P < 0.05) 18% and 29%, respectively. Torque or force and power decreased (P < 0.05) 31 60% (knee extension) and 37-56% (plantar flexion) while knee extensor and plantar flexor EMG activity decreased 31-38% and 28-35%, respectively following BR. Muscle atrophy in BRE was prevented (P > 0.05; knee extensors) or attenuated (-15%; plantar flexors). BRE maintained task-specific force, power and EMG activity. The decrease in non-task-specific torque was less (P < 0.05) than in BR. The present data imply that the triceps surae and quadriceps muscles show different responsiveness to long-term bed rest with or without resistance exercise. The results also suggest that designing in-flight resistance exercise protocols for space travellers is complex and must extend beyond preserving muscle only.

Adult↗
PubMed1998

Evidence for increased cardiac compliance during exposure to simulated microgravity.

We measured hemodynamic responses during 4 days of head-down tilt (HDT) and during graded lower body negative pressure (LBNP) in invasively instrumented rhesus monkeys to test the hypotheses that exposure to simulated microgravity increases cardiac compliance and that decreased stroke volume, cardiac output, and orthostatic tolerance are associated with reduced left ventricular peak dP/dt. Six monkeys underwent two 4-day (96 h) experimental conditions separated by 9 days of ambulatory activities in a crossover counterbalance design: 1) continuous exposure to 10 degrees HDT and 2) approximately 12-14 h per day of 80 degrees head-up tilt and 10-12 h supine (control condition). Each animal underwent measurements of central venous pressure (CVP), left ventricular and aortic pressures, stroke volume, esophageal pressure (EsP), plasma volume, alpha1- and beta1-adrenergic responsiveness, and tolerance to LBNP. HDT induced a hypovolemic and hypoadrenergic state with reduced LBNP tolerance compared with the control condition. Decreased LBNP tolerance with HDT was associated with reduced stroke volume, cardiac output, and peak dP/dt. Compared with the control condition, a 34% reduction in CVP (P = 0.010) and no change in left ventricular end-diastolic area during HDT was associated with increased ventricular compliance (P = 0.0053). Increased cardiac compliance could not be explained by reduced intrathoracic pressure since EsP was unaltered by HDT. Our data provide the first direct evidence that increased cardiac compliance was associated with headward fluid shifts similar to those induced by exposure to spaceflight and that reduced orthostatic tolerance was associated with lower cardiac contractility.

Animals↗
PubMed2001

Effect of simulated microgravity conditions on poly(ADP-ribose) polymerase activity in primary cultures of adult rat hepatocytes.

The possible involvement of poly(ADP-ribose) polymerase [PARP; E.C. 2.4.2.30] in the adaptive response to low-g conditions was studied in cultured adult rat hepatocytes exposed to simulated microgravity produced by the random positioning machine (RPM-3D-clinostat). Four different poly(ADP-ribose) polymerases (PARPs) have been identified recently. The best-studied member of this family is PARP-1, a highly conserved, multimodular 113 kDa protein. In multicellular organisms PARPs catalyze poly(ADP-ribose) synthesis from NAD+ to a number of structural and catalytic proteins. Moreover, PARP-1 can control its protein and DNA interactions by catalyzing its automodification with poly(ADP-ribose) molecules that can include up to 200 ADP-ribose residues and several branching points; by these polymers, PARP-1 may nocovalently interact with other proteins and alter their functions. PARP-1 binds to DNA and is activated by free ends interacting with several other DNA damage checkpoint proteins. Thus, PARPs may target specific signal network proteins via poly(ADP-ribose) and regulate their domain functions. Poly(ADP-ribosyl)ation plays a central role in genome stability and is involved in DNA replication and repair, gene expression, cell differentiation and transformation. We have shown that a loss of PARP-1 activity is a critical event in the early molecular steps of the hepatocarcinogenesis process. Moreover, a prompt increase in this enzymatic activity is linked not only to the presence of DNA free ends but is linked also to the start of DNA synthesis. More recently, we have reported that PARP-1 is involved in hormone-mediated gene expression in vitro and in vivo during rat liver regeneration.

Adaptation, Physiological↗
PubMedDate not supplied

Effect of simulated microgravity on testosterone and sperm motility in mice.

We examined changes in the serum testosterone level and in sperm in the testis and epididymis by using tail-suspended mice, which are a simulation model of the body fluid shift in space, to evaluate the possibility of spermatogenesis failure in space environment. We also studied pathological disorders of the testis in the tail-suspended mice. Tail suspension was imposed with a tail harness to a degree at which the hindlegs of mice did not touch the floor of the housing unit. In control mice, the tail was similarly fixed with a tail harness to impose the same stress, except that a hindleg remained on the floor. Body weight was not significantly different between the 2 groups during 7 days, and testicular weight was significantly different. The testosterone level was significantly lower in the tail-suspended group (0.71 +/- 1.24 ng/mL) than in the control group (2.38 +/- 3.50 ng/mL; P <.05). Microscopy with hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) staining showed a small proportion of seminiferous tubules with impairment of spermatogenic function in the tail-suspended group, and multinucleated giant cells were occasionally noted. Terminal deoxynucleotidyl tranferase-mediated nick end-labeling staining revealed positive cells even in animals in which impairment was considered to be mild based on HE and PAS staining. Many cells showed intense p53 immunostaining compared to the control group, with more intense staining of the nucleus in the tail-suspended group. The proportion of motile sperm was slightly but not significantly reduced in the tail-suspended group. However, the mean movement velocity of the motile spermatozoa was significantly decreased.

Animals↗
PubMed1997

Dynamics of a microcarrier particle in the simulated microgravity environment of a rotating-wall vessel.

Rotating-wall vessel (RWV), a low-shear, low turbulence microcarrier culture system provides a simulated microgravity environment suitable for 3-dimensional tissue culture. In this paper, the motion of a microcarrier particle in the rotating fluid has been analytically/numerically studied. If the microcarrier is less dense than the surrounding liquid medium, it eventually migrates towards an equilibrium state in the fluid. This state corresponds to a stationary location in the inertial frame of reference or equivalently, a circular orbit about the rotational axis in a rotating frame. If the particle is denser, it may move away indefinitely to reach or collide with the outer wall of the rotating vessel (outer boundary of the rotating fluid). Such a collision may damage the cells and could be undesirable for tissue culture. We have calculated migration times for a denser microcarrier to reach the outer wall of the vessel. Several factors--rotational speed, fluid viscosity, density difference between that of the microcarrier and the fluid, microcarrier radius, and the initial position of the microcarrier--were found to affect this migration time. We have also evaluated the variation of the fluid shear stress on the microcarrier surface. Decreasing the density difference between the microcarrier and the fluid, and decreasing the size of the microcarrier, can both decrease the maximum shear stress. The results for a solid, a hollow, and a hollow-porous microcarrier show that with a denser microcarrier material, the hollow or hollow-porous spherical microcarriers are preferable in order to increase the suspension time and decrease the maximum shear stress. The results of this study are thought to be useful for the development of optimal conditions for cell growth and metabolism in RWVs.

Cell Culture Techniques↗
PubMed2002

"DRY" immersion induces neural and contractile adaptations in the human triceps surae muscle.

The effects of 7-days of simulated spaceflight, achieved with the technique of "dry" water immersion, on human triceps surae muscle function have been investigated in six subjects. After immersion, the maximal voluntary contraction (MVC) was reduced by 19% (p<0.01), and the electrically evoked (150 Hz) maximal tetanic contraction (Po) was reduced by 8% (p>0.05). The difference between Po and MVC expressed as a percentage of Po and referred to as force deficiency has also been calculated. The force deficiency increased by 44% (p<0.01) after immersion. The decrease in Po was associated with increased maximal rates of tension development (7.2%) and of tension relaxation. The twitch time-to-peak was not significantly changed, and half relaxation and total contraction time were decreased by 5% and 3%, respectively, but the twitch tension (Pt) was not significantly changed and the Pt/Po ratio was decreased by 9%. The 60-s intermittent contractions (50 Hz) decreased tetanic force to 57% (p<0.05) of initial values, but force reduction was not significantly different in the two fatigue tests: fatigue index was 36.2 +/- 5.4% vs. 38.6 +/- 2.8%, respectively (p>0.05). While identical force reduction was present in the two fatigue test it would appear that concomitant electrical failure was considerably different. Comparison of the electrical and mechanical responses alterations recorded during voluntary contractions, and in contractions evoked by electrical stimulation of the motor nerve, suggests that immersion not only modifies the peripheral processes associated with contraction, but also changes central and/or neural command of the contraction. At peripheral sites, it is proposed that the intracellular processes of contraction play a role in the contractile impairment recorded during immersion.

Adaptation, Physiological↗
PubMed2000

Vascular hyporesponsiveness in simulated microgravity: role of nitric oxide-dependent mechanisms.

Simulated microgravity depresses the ability of arteries to constrict to norepinephrine (NE). In the present study the role of nitric oxide-dependent mechanisms on the vascular hyporesponsiveness to NE was investigated in peripheral arteries of the rat after 20 days of hindlimb unweighting (HU). Blood vessels from control rats and rats subjected to HU (HU rats) were cut into 3-mm rings and mounted in tissue baths for the measurement of isometric contraction. Mechanical removal of the endothelium from carotid artery rings, but not from aorta or femoral artery rings, of HU rats restored the contractile response to NE toward control. A 10-fold increase in sensitivity to ACh was observed in phenylephrine-precontracted carotid artery rings from HU rats. In the presence of the nitric oxide synthase (NOS) substrate L-arginine, the inducible NOS inhibitor aminoguanidine (AG) restored the contractile responses to NE to control levels in the femoral, but not carotid, artery rings from HU rats. In vivo blood pressure measurements revealed that the peak blood pressure increase to NE was significantly greater in the control than in the HU rats, but that to AG was less than one-half in control compared with HU rats. These results indicate that the endothelial vasodilator mechanisms may be upregulated in the carotid artery, whereas the inducible NOS expression/activity may be increased in the femoral artery from HU rats. These HU-mediated changes could produce a sustained elevation of vascular nitric oxide levels that, in turn, could contribute to the vascular hyporesponsiveness to NE.

Acetylcholine↗
PubMed2000

Effects of three days of dry immersion on muscle sympathetic nerve activity and arterial blood pressure in humans.

The present study was performed to determine how sympathetic function is altered by simulated microgravity, dry immersion for 3 days, and to elucidate the mechanism of post-spaceflight orthostatic intolerance in humans. Six healthy men aged 21-36 years old participated in the study. Before and after the dry immersion, subjects performed head-up tilt (HUT) test to 30 degrees and 60 degrees (5 min each) with recordings of muscle sympathetic nerve activity (MSNA, by microneurography), electrocardiogram, and arterial blood pressure (Finapres). Resting MSNA was increased after dry immersion from 23.7+/-3.2 to 40.9+/-3.0 bursts/min (p<0.005) without significant changes in resting heart rate (HR). MSNA responsiveness to orthostasis showed no significant difference but HR response was significantly augmented after dry immersion (p<0. 005). A significant diastolic blood pressure fall at 5th min of 60 degrees HUT was observed in five orthostatic tolerant subjects despite enough MSNA discharge after dry immersion. A subject suffered from presyncope at 2 min after 60 degrees HUT. He showed gradual blood pressure fall 10 s after 60 degrees HUT with initially well-maintained MSNA response and then with a gradually attenuated MSNA, followed by a sudden MSNA withdrawal and abrupt blood pressure drop. In conclusion, dry immersion increased MSNA without changing MSNA response to orthostasis, and resting HR, while increasing the HR response to orthostasis. Analyses of MSNA and blood pressure changes in orthostatic tolerant subjects and a subject with presyncope suggested that not only insufficient vasoconstriction to sympathetic stimuli, but also a central mechanism to induce a sympathetic withdrawal might play a role in the development of orthostatic intolerance after microgravity exposure.

Adult↗
PubMed1998

Effects of the 120 days of head-down bed rest on cytokine secretion and its in vitro modulation by glucocorticoids.

Antiorthostatic hypokinesia or head-down bed rest (HDBR), is a ground-based model system used to simulate some of the physioloical responses observed during space flight. Several studies involving humans and animals have demonstrated the effects of HDBR on different physioloical systems. HDBR produced a large thoracic fluid shift similar to that reported for space flight. Exposure to the combination of -6 degrees HDBR, emotional stress, and hypergravity led to an elevation of plasma histamine and serotinin and a dramatic decrease in the concentration of prostaglandins E, F2-alpha, and erthropoietin. These responses indicated the HDBR produces significant alterations in the neuroendocrine regulatory pathways. The proliferative response of immune cells in response to activators was significantly enhanced in antiorthostatically suspended mice; plasma corticosterone also was higher but splenic natural killer cell cytotoxicity remained unchanged after suspension. Bone-resporbing activity of supernatatants increased in mitogen-stimulated PBMC cultures of subjects exposed to -5 degrees HDBR for 370 days of HDBR. Proliferative activity of PBMCs had declined at the end of a 320-day HDBR and during the initial days of recovery, but the numbers of active rosette-forming T cells increased. These and other results suggest that most stress-induced immune changes are neuroendocrine modulated, and that corticosteroids play a significant role in this modulation. It is expected that HDBR-induced immune changes could result from similar mechanisms. In this study, we investigated the effect of 120 days of HDBR on Type-1 vs. Type-2 cytokine equilibrium in mitogen-activated PBMC culture, and how these reactions may correlate with changes in the neuroendocrine status.

Adult↗
PubMed2005

Functional alterations in cerebrovascular K(+) and Ca(2+) channels are comparable between simulated microgravity rat and SHR.

Exposure to microgravity leads to a sustained elevation in transmural pressure across the cerebral vasculature due to removal of hydrostatic pressure gradients. We hypothesized that ion channel remodeling in cerebral vascular smooth muscle cells (VSMCs) similar to that associated with hypertension may occur and play a role in upward autoregulation of cerebral vessels during microgravity. Sprague-Dawley rats were subjected to 4-wk tail suspension (Sus) to simulate the cardiovascular effect of microgravity. Large-conductance Ca(2+)-activated K(+) (BK(Ca)), voltage-gated K(+) (K(V)), and L-type voltage-dependent Ca(2+) (Ca(L)) currents of Sus and control (Con) rat cerebral VSMCs were investigated with a whole cell voltage-clamp technique. Under the same experimental conditions, K(V), BK(Ca), and Ca(L) currents of cerebral VSMCs from adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were also investigated. K(V) current density decreased in Sus rats vs. Con rats [1.07 +/- 0.14 (n = 22) vs. 1.31 +/- 0.28 (n = 16) pA/pF at +20 mV (P < 0.05)] and BK(Ca) and Ca(L) current densities increased [BK(Ca): 1.70 +/- 0.37 (n = 23) vs. 0.88 +/- 0.22 (n = 19) pA/pF at +20 mV (P < 0.05); Ca(L): -2.17 +/- 0.21 (n = 35) vs. -1.31 +/- 0.10 (n = 26) pA/pF at +10 mV (P < 0.05)]. Similar changes were also observed in SHR vs. WKY cerebral VSMCs: K(V) current density decreased [1.03 +/- 0.33 (n = 9) vs. 1.62 +/- 0.64 (n = 9) pA/pF at +20 mV (P < 0.05)] and BK(Ca) and Ca(L) current densities increased [BK(Ca): 2.54 +/- 0.47 (n = 11) vs. 1.12 +/- 0.33 (n = 12) pA/pF at +20 mV (P < 0.05); Ca(L): -3.99 +/- 0.53 (n = 12) vs. -2.28 +/- 0.20 (n = 10) pA/pF at +20 mV (P < 0.05)]. These findings support our hypothesis, and their impact on space cardiovascular research is discussed.

Animals↗
PubMedDate not supplied

Tri-dimensional prostate cell cultures in simulated microgravity and induced changes in lipid second messengers and signal transduction.

The high aspect rotating-wall vessel (HARV) was designed to cultivate cells in an environment that simulate microgravity. We studied previously the effects of HARV cultivation on DU-145 human prostate carcinoma cells. We determined that HARV cultivation produced a less aggressive, slower growing, less proliferative, more differentiated and less pliant cell than other cell cultivation methods. The result was a 3-dimensional (3D) growth model of prostate cancer which mimics in vivo tissue growth. This work examines the signal transduction-second messenger pathways existing temporarily in these HARV cells and correlates these features with the special properties in growth and 3D spheroid formation. We found an initial very active ceramide, a diacylglycerol increase together with increases in PI-PLC and PLA(2) a central defect in PLD (no phosphatic acid or phosphatidylethanol at any time during 15 days of HARV cultivation). There is a cross-talk between ceramide and PI3K pathways with activation of PI3K, after 6 days of HARV growth concomitant with down-regulation of ceramide. At this time, there is also an increase of cAMP (seen by increases in arachidonic acid). Taken together these results can explain the 3D organoid-like growth. We therefore developed a model for growth in HARV prostate cancer cells which involve temporal "switches" between second messengers, activation and cross-talk between multiplicity of signaling pathways and a central defect in PLD pathways. Essential to the late slow growth, and 3D organotypic formation are the apoptotic, anti-survival, anti-proliferation and differentiation pathways in the first days of HARV, with growth of "new" different types of prostate cancer cells which set-up for later "switch" in ceramide-PI3K to survival and proliferation.

Cell Culture Techniques↗
PubMed2002

Nutritional interventions related to bone turnover in European space missions and simulation models.

Low energy intake, low calcium intake, low plasma 25-hydroxy-vitamin D or low calcitriol levels, and high salt intake might support the development of space osteoporosis. Therefore, my colleagues and I monitored the daily energy and calcium intakes in eight astronauts during their respective space missions (Spacelab D2, Euromir 94, Euromir 95). In most of these astronauts, energy intake was reduced by more than 20% compared with their calculated energy expenditure. In all three missions, the average daily calcium intake of the eight astronauts was 25% lower than the German recommended daily allowances of 900 mg/d for healthy people without osteoporosis risk. In some astronauts, the calcium intake was extremely low at 53 and 74 mg/d. Sodium intake in these astronauts varied from 39 mEq/d to a very high intake of 462 mEq/d. As a consequence of these results, we examined in the 21-d Mir 97 mission a preventative dietary approach of high calcium intake of at least 1000 mg/d with vitamin D supplementation (650 IU/d of Ergocalciferol) and constant sodium intake (180 mEq/d). Total serum calcium concentration and urinary calcium excretion significantly increased during this mission. Synthesis of 25-OH-cholecalciferol synthesis was markedly reduced because of inadequate ultraviolet light, whereas total 25-OH-Vitamin D levels were unchanged. However, parathyroid hormone and calcitriol levels decreased significantly. Sodium excretion decreased significantly, resulting in positive sodium balances. Based on these results, dietary calcium and vitamin D do not stabilize bone turnover because markers of bone formation were reduced and markers of bone resorption were increased. We concluded that, in contrast to terrestrial conditions, adequate or even high calcium and vitamin D intakes during microgravity do not efficiently counteract the development of space osteoporosis. Conversely, vitamin K (Konakion) seemed to counteract microgravity-induced reduction of bone formation markers. In the 179-d Euromir 95 mission, investigators administered 10 mg of vitamin K from inflight day 86 to day 136 in one astronaut. During and after supplementation, bone formation markers increased significantly during this part of the mission. Therefore, vitamin K seems to play a significant role in bone turnover during space flight.

Aerospace Medicine↗
PubMed2004

Effects of support stimulation on human soleus fiber characteristics during exposure to "dry" immersion.

In this study the model of 7-day dry immersion (DI) was used. 17 male volunteers (23-29 years old) were divided in 2 groups: (i) 7-day DI without support (DI, n=9), (ii) 7-day DI using support stimulation (DIS, n=8). Support stimulator device exerted pressure of 0.2 +/- 0.15 kg/cm2 upon the plantar support zones simulating the walking pattern 6 times a day for 20 minutes of every hour: 10 minutes at a speed of 75 steps/min and 10 minutes at a speed of 120 steps/min. M. soleus biopsy was performed before and immediately after DI. The m. soleus fiber myosin heavy chain (MHC) profile, myofiber cross-sectional area (CSA) and total protein concentration were analyzed in frozen serial sections. In addition, NO-synthase 1 (NOS1) levels indicative of normal muscle cell signaling were analyzed by western blotting in 4 persons in each group. After dry immersion, percentage of muscle fibers containing type I MHC decreased by 6% (p<0.05) in group DI, but was not changed significantly in group DIS. Percentage of the type IIa fibers was significantly altered in none of the groups. Type I fiber CSA decreased by 24.4% (p<0.05) in group DI. No significant changes of type I fiber CSA were found in group DIS. CSA of the type IIa fibers significantly altered in none of the groups. The total protein concentration was found increased by 17.6% in group DI and by 21% in group DIS. The increased total protein content in group DI suggests a diminution of fiber CSA attributed to the loss of non-protein component of fibers. NOS1 decreased by 35.6% in group DI and increased by 58.1% in group DIS. We conclude that 7 days in dry immersion lead to reduction in the type I muscle fiber percentage, loss of the non-protein component and decline in NOS1. These changes were clearly prevented by the support stimulation protocol applied during the DI period.

Adult↗
PubMed2003

Staying in bed to benefit ESA's astronauts and Europe's citizens.

Since Yuri Gagarin's historic first flight into space in April 1961, it has quickly become evident that the space environment influences the human body in many different ways and causes it to adapt in ways that can lead to problems when returning to Earth's gravity. Much research has been performed in the meantime and our understanding of what happens to our bodies in space improved considerably during the Mir space station and Space Shuttle/Spacelab era. However, many questions, particularly regarding how to counteract those changes that we now know take place, still need to be addressed through studies on the International Space Station (ISS) and through simulations on the ground. As we enter an era in which crews will spend longer periods in space on the ISS and of longer term plans by almost every space-faring nation for missions to Mars, it is clear that much more knowledge is needed, and quickly. Although a few hundred men and women have already travelled into space, the operating environment severely limits the amount of systematic research that can be performed--a situation that is unlikely to change. Other avenues for addressing specific scientific questions in a controlled research environment must therefore be found. One of these complementary alternatives is head-down-tilt bed-rest studies in which volunteers are confined to beds that are tilted -6 deg below the horizontal at the head end. Every activity, including eating, reading, showering, etc., is performed in this position for the duration of the study. This leads to changes in the human body that are very similar to those seen during spaceflight, such as bone-mass and muscle-mass loss, cardiovascular and neuro-sensory deconditioning. The controlled bed-rest setting therefore allows meaningful research into the bodily consequences of spaceflight and possible countermeasures. It also gives the scientific community interested in space-related medical research more ready access to a clinical model. The benefits of these studies go far beyond their space application. Patients bed-ridden because of illness or accidents suffer the same symptoms and can thus also profit from the studies. As a clear indication of this link, the clinicians and researchers involved in the bed-rest campaigns typically spend the majority of their time exploring "terrestrial" problems.

Adaptation, Physiological↗
PubMed2005

[Reactivity of pulmonary arteries and thoracic aortae in rats under tail-suspension and the effects of NOS inhibitor].

OBJECTIVE: To further disclose mechanisms in adaptation of pulmonary and systemic arteries to simulated microgravity (SM), so as to elucidate the mechanisms accounting for orthostatic intolerance after SM, and to explore a new kind of countermeasure for orthostatic intolerance. METHOD: 300 tail suspended (TS) rats were used as the model to simulate the physiological effects of microgravity. Vasoreactivity changes of rings sectioned from pulmonary artery (PA) and thoracic aorta (TA) to 68 mmoles/L KCl, plus phenylephrine (PE) and acetylcholine (ACh) were observed after 7 d and 14 d tail-suspension. After preconditioning with 10(-5) moles/L N-nitro-L-arginine methyl ester (L-NAME) for 20 min, vasoreactivity changes of PA and TA to PE and ACh were respectively repeated. RESULT: The contractile responsiveness of PA and TA to KCl and PE decreased significantly or very significantly after TS7 d and TSI4 d. The dilatory reactivity of PA and TA to ACh after TS7 d had a significant or very significant increase, but reactivity of PA showed no change and TA showed only a tendency to increase after TS14 d. After preconditioning with 10(-5) moles/L L-NAME, responsiveness of PA to PE after TS7 d and TS14 d had no difference among the three groups, but responsiveness of TA to PE after TS7 d and TS14 d had a significant decrease. The dilatory reactivity of PA after TS7 d decreased significantly or very significantly, and the remains showed no significant change. CONCLUSION: The decrease of contractile responsiveness of PA and TA might be due to the increased dilatory function of the endothelial cells. The fact that 10(-5) moles/L L-NAME reversed the decrease of contractile responsiveness of PA and partly of TA after tail suspension implicates that there might be an inhibitory action on the dilatory function of the endothelial cells. The NOS inhibitors may be helpful in preventing orthostatic intolerance.

Acetylcholine↗
PubMed2002

Changes in organ perfusion and weight ratios in post-simulated microgravity recovery.

Head-down tilt models have been used as ground-based simulations of microgravity. Our previous animal research has demonstrated that there are significant changes in fluid distribution within 2 h after placement in a 45 degrees head-down tilt (45HDT) position and these changes in fluid distribution were still present after 14 days of 45HDT. Consequently, we investigated changes in fluid distribution during recovery from 16 days of 45HDT. Changes in radioactive tracer distribution and organ/body weight ratio were examined in rats randomly assigned to a 45HDT or prone control group. The 45HDT rats were suspended for 16 days and then allowed to recover at the prone position 0, 77, 101, or 125 h post-suspension. Animals were injected with technetium-labeled diethylenetriamine pentaacetate (99mTcDTPA, MW=492 amu, physical half-life of 6.02 h) and then killed 30 min post-injection. Lungs, heart, liver, spleen, kidneys, and brain were harvested, weighed, and measured for radioactive counts. Statistical analyses included two-way analysis of variance (ANOVA) that compared 45HDT versus controls at the four experimental time points. The organ weight divided by the body weight ratio for the brain, heart, kidneys and liver in the 45HDT rats was significantly different than the control rats, regardless of time (treatment). There was no difference between the different time points (time). The average 99mTcDTPA count divided by the organ weight ratio values for the heart, liver, and spleen were significantly higher in the 45HDT group than the control group. The average counts for the heart and spleen were significantly higher at 77, 101, and 125 h than at time zero. We conclude that the major organs have different recovery patterns after 45HDT for 16 days in the rat.

Adaptation, Physiological↗
PubMed2004

Differential expression of nitric oxide synthases (NOS 1-3) in human skeletal muscle following exercise countermeasure during 12 weeks of bed rest.

Adaptive changes of major body systems in astronauts during spaceflight can be simulated by strict anti-orthostatic head-down tilt (HDT) bed rest (BR), a ground-based microgravity (microG) model that provides a meaningful opportunity to study atrophy mechanisms and possible countermeasures under controlled experimental conditions. As nitric oxide (NO) signaling is linked to muscle activity, we investigated altered expression of the three major isoforms of nitric oxide synthase (NOS 1-3) at cellular compartments during prolonged HDT BR without (control group) and with resistance exercise interventions (exercise group) using a flywheel ergometer (FWE). Atrophy detected in mixed (fast-slow) m. vastus lateralis (VL) and slow-type m. soleus (SOL) myofiber Types I and II (minus 35-40% of myofiber cross-sectional area) was prevented by FWE training. Concomitant to muscle atrophy, reduced NOS 1 protein and immunostaining was found in VL not in SOL biopsies. In trained VL, NOS 1 protein and immunostaining at myofibers II were significantly increased at the end of BR. Exercise altered NOS 2/caveolin 3 co-immunostaining patterns of subsarcolemmal focal accumulations in VL or SOL myofibers, which suggests reorganization of sarcolemmal microdomains. In trained VL, increased capillary-to-fiber (C/F) ratio and NOS 3 protein content were documented. Activity-linked NO signaling may be widespread in skeletal muscle cellular compartments that may be directly or indirectly impacted by adequate exercise countermeasure protocols to offset the negative effects induced by disuse, immobilization, or extended exposure to microgravity.

Adult↗