Microgravity and simulated microgravity (SM) lead to important changes in orthostatic tolerance (OT), the autonomic nervous system (ANS), and the volume-regulating systems. After one is exposed to ...microgravity or SM, a period of readaptation to gravity is known to take place, but it is not certain if orthostatic function returns to baseline within the initial recovery and what mechanisms are involved. We hypothesized that after a period of recovery, OT, ANS, and volume-regulating systems would return to pre-SM levels.
To test this hypothesis, 24 healthy men were placed on a constant diet for 3 to 5 days, after which a tilt-stand test (pre-TST) was performed. The TST was repeated after 14 to 16 days of head-down tilt bed rest (HDTB) (post-TST) and a 3-day period of recovery (rec-TST), at which times measurements of renal, cardioendocrine, and cardiovascular systems were conducted.
Presyncope occurred in 46% of subjects pre-TST, in 72% post-TST, and in 23% during rec-TST. OT was significantly better during the recovery period than at baseline (p = .03). There was a significant decrease in urinary sodium and potassium excretion, along with a decrease in plasma renin activity and serum and urine aldosterone compared with baseline. Serum norepinephrine and sympathetic responsiveness remained below baseline values.
In summary, OT improved compared with baseline after a period of readaptation. Retention of electrolytes (sodium, potassium) could be involved. These findings indicate that recovery after SM is not simply a gradual return to baseline values but is instead a dynamic process reflecting interaction of multiple regulatory systems.
The purpose of this study was to determine whether hindlimb suspension (which simulates the effects of microgravity) results in impaired hemodynamic responses to heat stress or alterations in ...mesenteric small artery sympathetic nerve innervation.
Over 28 d, 16 male Sprague-Dawley rats were hindlimb-suspended, and 13 control rats were housed in the same type of cage. After the treatment, mean arterial pressure (MAP), colonic temperature (Tcol), and superior mesenteric and iliac artery resistances (using Doppler flowmetry) were measured during heat stress exposure to 42 degrees C until the endpoint of 80 mm Hg blood pressure was reached (75 +/- 9 min); endpoint Tcore = 43.6 +/- 0.2 while rats were anesthetized (sodium pentobarbital, 50 mg x kg(-1) BW).
Hindlimb-suspended and control rats exhibited similar increases in Tcol, MAP, and superior mesenteric artery resistance, and similar decreases in iliac resistance during heat stress (endpoint was a fall in MAP below 80 mm Hg). Tyrosine hydroxylase immunostaining indicated similar sympathetic nerve innervation in small mesenteric arteries from both groups.
Hindlimb suspension does not alter the hemodynamic or thermoregulatory responses to heat stress in the anesthetized rat or mesenteric sympathetic nerve innervation, suggesting that this sympathetic pathway is intact.
Our objective was to determine the effects of a clenbuterol (CB) treatment orally administered (2 mg per kg) to rats submitted to 14 days of hindlimb unloading (HU). The morphological and the ...contractile properties as well as the myosin heavy chain isoforms contained in each fiber type were determined in whole soleus muscles. As classically described after HU, a decrease in muscle wet weight and in body mass associated with a loss of muscular force, an evolution of the contractile parameters towards those of a fast muscle type, and the emergence of fast myosin heavy chain isoforms were observed. The CB treatment in the HU rats helped reduce the decrease in 1) muscle and body weights, 2) force and 3) the proportion of slow fibers, without preventing the emergence of fast myosin isoforms. Clenbuterol induced a complex remodelling of the muscle typing promoting the combination of both slow and fast myosin isoforms within one fiber. To conclude, our data demonstrate that CB administration partially counteracts the effects produced by HU, and they allow us to anticipate advances in the treatment of muscular atrophy.Key words: β
2
agonist, clenbuterol, soleus, contractile parameters, myosin, immunohistochemistry, simulated microgravity, countermeasure.
Measures to attenuate muscle atrophy in rats in response to stimulated microgravity hindlimb suspension (HS) have been only partially successful. In the present study, hypophysectomized rats were in ...HS for 7 days, and the effects of recombinant human growth hormone (GH), exercise (Ex), or GH+Ex on the weights, protein concentrations, and fiber cross-sectional areas (CSAs) of hindlimb muscles were determined. The weights of four extensor muscles, i.e., the soleus (Sol), medial (MG) and lateral (LG) gastrocnemius, and plantaris (Plt), and one adductor, i.e., the adductor longus (AL), were decreased by 10-22% after HS. Fiber CSAs were decreased by 34% in the Sol and by 17% in the MG after HS. In contrast, two flexors, i.e., the tibialis anterior (TA) and extensor digitorum longus (EDL), did not atrophy. In HS rats, GH treatment alone maintained the weights of the fast extensors (MG, LG, Plt) and flexors (TA, EDL) at or above those of control rats. This effect was not observed in the slow extensor (Sol) or AL. Exercise had no significant effect on the weight of any muscle in HS rats. A combination of GH and Ex treatments yielded a significant increase in the weights of the fast extensors and in the CSA of both fast and slow fibers of the MG and significantly increased Sol weight and CSA of the slow fibers of the Sol. The AL was not responsive to either GH or Ex treatments. Protein concentrations of the Sol and MG were higher only in the Sol of Ex and GH + Ex rats.
Although a wealth of evidence supports the hypothesis that some functions of the nervous system may be altered during exposure to microgravity, the possible changes in basic neuronal physiology are ...not easy to assess. Indeed, few studies have examined whether microgravity affects the development of neurons in culture. In the present study, a suspension of dissociated cortical cells from rat embryos were exposed to 24 h of simulated microgravity before plating in a normal adherent culture system. Both preexposed and control cells were used after a period of 7–10 d in vitro. The vitality and the level of reactive oxygen species of cultures previously exposed did not differ from those of normal cultures. Cellular characterization by immunostaining with a specific antibody displayed normal neuronal phenotype in control cells, whereas pretreatment in simulated microgravity revealed an increase of glial fibrillary acidic protein fluorescence in the elongated stellate glial cells. Electrophysiological recording indicated that the electrical properties of neurons preexposed were comparable with those of controls. Overall, our results indicate that a short time of simulated microgravity preexposure does not affect dramatically the ability of dissociated neural cells to develop and differentiate in an adherent culture system.
To observe the effects of simulated microgravity on beta islet cell culture, we have compared the survival rates and the insulin levels of the isolated rat islet cells cultured at the micro- and ...normal gravity conditions. The survival rates of the cells cultured were determined by acridine orange-propidium iodide double-staining on day 3, 7 and 14. The morphology of the cells was observed by electron microscopy. Insulin levels were measured by radioimmune assays. Our results show that the cell number cultured under the microgravity condition is significantly higher than that under the routine condition (P<0.01). Some tubular structure, possibly for the transport of nutrients, were formed intercellularly in the microgravity cultured group on day 7 after the cultivation shown by transmission electron microscopy. There were also abundant secretion particles and mitochondria in the cytoplasma of the cells. Scanning electron microscopy showed there were holes formed between each islets, possibly the connecting points with the nutrients transport tubules. The microgravity cultured group also has the higher insulin levels in the media when compared with the control group (P< 0.01). Our results indicate that microgravity cultivation of islet cells has advantages over the routine culture methods.
To reveal subtle morphological changes in the eye during simulated microgravity for spaceflights, we measured subfoveal choroidal thickness and foveal retinal thickness during 10 degrees head-down ...tilt (HDT). We hypothesized that elevated ophthalmic vein pressure during simulated microgravity increases subfoveal choroidal thickness via enlargement of the choroidal vasculature and greater choroidal blood volume.
The right eyes of nine healthy subjects (seven men, two women) were examined. Subfoveal choroidal thickness and foveal retinal thickness were measured using spectral domain-optical coherence tomography in the sitting position, and after 15 and 30 min of 10 degrees HDT. Intraocular pressure was also measured.
Mean subfoveal choroidal thickness (+/- SEM) increased from 300 +/- 31 microm in the sitting position to 315 +/- 31 microm with 15-min HDT, and 333 +/- 31 microm with 30-min HDT. However, no change in foveal retinal thickness was observed (228 +/- 9 microm in the sitting position, 228 +/- 10 microm with 15-min HDT and 228 +/- 9 microm with 30-min HDT). Intraocular pressure increased from 14 +/- 1 mmHg in the sitting position to 21 +/- 2 mmHg with 30-min HDT (54 +/- 6%, N = 5).
Subfoveal choroidal thickness and intraocular pressure were increased by HDT during simulated microgravity, although no change in foveal retinal thickness was observed.
Rotating bioreactors designed at NASA's Johnson Space Center were used to simulate a microgravity environment in which to study secondary metabolism. The system examined was beta-lactam antibiotic ...production by Streptomyces clavuligerus. Both growth and beta-lactam production occurred in simulated microgravity. Stimulatory effects of phosphate and L-lysine, previously detected in normal gravity, also occurred in simulated microgravity. The degree of beta-lactam antibiotic production was markedly inhibited by simulated microgravity.
The growth and repair of adult skeletal muscle are due in part to activation of muscle precursor cells, commonly known as satellite cells or myoblasts. These cells are responsive to a variety of ...environmental cues, including mechanical stimuli. The overall goal of the research is to examine the role of mechanical signalling mechanisms in muscle growth and plasticity through utilisation of cell culture systems where other potential signalling pathways (i.e. chemical and electrical stimuli) are controlled. To explore the effects of decreased mechanical loading on muscle differentiation, mammalian myoblasts are cultured in a bioreactor (rotating cell culture system), a model that has been utilised to simulate microgravity. C2C12 murine myoblasts are cultured on microcarrier beads in a bioreactor and followed throughout differentiation as they form a network of multinucleated myotubes. In comparison with three-dimensional control cultures that consist of myoblasts cultured on microcarrier beads in teflon bags, myoblasts cultured in the bioreactor exhibit an attenuation in differentiation. This is demonstrated by reduced immunohistochemical staining for myogenin and alpha-actinin. Western analysis shows a decrease, in bioreactor cultures compared with control cultures, in levels of the contractile proteins myosin (47% decrease, p < 0.01) and tropomyosin (63% decrease, p < 0.01). Hydrodynamic measurements indicate that the decrease in differentiation may be due, at least in part, to fluid stresses acting on the myotubes. In addition, constraints on aggregate size imposed by the action of fluid forces in the bioreactor affect differentiation. These results may have implications for muscle growth and repair during spaceflight.
Two prominent theories to explain the physiological effects of microgravity relate to the cascade of changes associated with the cephalic shifts of fluids and the absence of tissue deformation ...forces. One-g experiments for humans used bed rest and the head-down tilt (HDT) method, while animal experiments have been conducted using the tail-suspended, head-down, and hindlimbs non-weightbearing model. Because of the success of the HDT approach with rats to simulate the gravitational effects on the musculoskeletal system exhibited by humans, the same model has been used to study the effects of gravity on the cardiopulmonary systems of humans and other vertebrates. Results to date indicate the model is effective in producing comparable changes associated with blood volume, erythropoiesis, cardiac mass, baroreceptor responsiveness, carbohydrate metabolism, post-flight VO2max, and post-flight cardiac output during exercise. Inherent with these results is the potential of the model to be useful in investigating responsible mechanisms. The suspension model has promise in understanding the capillary blood PO2 changes in space as well as the arterial PO2 changes in subjects participating in a HDT experiment. However, whether the model can provide insights on the up-or-down regulation of adrenoreceptors remains to be determined, and many investigators believe the HDT approach should not be followed to study gravitational influences on pulmonary function in either humans or animals. It was concluded that the tail-suspended animal model had sufficient merit to study in-flight and post-flight human physiological responses and mechanisms.
PDF
