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PubMed1998

Comparison of excitability parameters and sodium channel behavior of fast- and slow-twitch rat skeletal muscles for the study of the effects of hindlimb suspension, a model of hypogravity.

When mammals are constrained to hypogravity, their neuromuscular apparatus undergoes modifications which rend difficult postural maintenance and muscular activity upon the return to normal gravitational conditions. Muscle atrophy and differetial gene expression are particularly evident in slow-twitch antigravity muscles such as the soleus. During hypogravity, most of the metabolic and contractile properties characteristic of slow-twitch muscles shift toward to those of fast-twitch muscles. For example, the expression of the fast isoforms of both the myosin heavy-chain and the sarcoplasmic reticulum calcium pump increases in slow-twitch muscle during hypogravity. Thus, modifications of the contractile machinery and calcium handling are likely to be involved in the hypogravity-induced slow-twitch muscle impariment. Fast- and slow-twitch muscles differ also in their electrical properties. Resting membrane potential (RMP) is more negative by about 10 mV in fast muscles compared to slow ones. Differences in action potential (AP) shape as well as in the number of elicitable APs have been also observed between both muscle types, which may reslut from the reported differences in chloride conductance and sodium current. Little is known about the potential modification fo muscle electrical properties during hypogravity, apart a negative shift of the RMP in soleus muscle. Thus this study was performed at the aim to compare the excitability parameters and sodium channel behavior of rat fast-twitch and slow-twitch muscle fibers. The characterization of these properties specific for each muscle-type will give us the basis for the study of the effect of hypogravity.

Action Potentials↗
PubMed1998

Insight into mechanisms of reduced orthostatic performance after exposure to microgravity: comparison of ground-based and space flight data.

Since the beginning of human spaceflight, the value of understanding mechanisms of physiological adaptation to microgravity became apparent to life scientists who were interested in maintining crew health and developing countermeasures agains adverse effects of the mission. However, several characteristics associated the the logistics of spaceflight presented significant limitations to the scientific study of human adaptation to microgravity. Because space missions are so infrequent and involve minimal numbers of crewmembers, meaninful statistical analysis of data are limited. Reproducibility of results from spaceflight experiments is difficult to assess since there are few repeated space missions involving the same crewmembers. Since the emphasis of space missions is placed on operations, experiments are compromised without adequate control over various factors (e.g., time, diet, physical activities, etc.) that can impact measured responses. With the mimimal opportunity to collect spaceflight data, there is a high risk of experiments that simultaneously interfere with other experiments by the increasing demand on the crewmembers to participate in mumerous experiments proposed by multiple investigators. The technology and ability to measure physiological functions necessary to test specific hypotheses can be severely limited by physical space and power constraints of the space enviroment. Finally, technical and logistical aspects of space missions such as launch delays, extended missions, and inflight operational emergencies can significantly compromise the timing and control of experiments. These limitations have stimulated scientists to develop ground-based analogs of microgravity in an effort to investigate the effects of spaceflight on physiological function in a controlled experimental setting. The purpose of this paper is to provide a selected comparison of data collected from ground-based experiments with those obtained from spaceflight in an effort to assess the adequacy of ground analogs of actual flight for the study of human physiological adaptation to microgravity. Specifically, results from ground and spaceflight will be used to provide insight into mechanisms underlying adaptations of blood pressure regulation and reduced orthostatic performance to the microgravity environment.

Adaptation, Physiological↗
PubMed1998

Neuronal responses to vector-averaged gravity: a search for gravisensing and adaptation mechanisms--a preliminary report.

This paper serves as a milepost in our work using the clinostat as a tool for mimicking certain aspects of altered gravity conditions (vector-nulled gravity) in order to gain insights into the adaptation of cells (and hence organisms) to the microgravity environment of space. I review here recent data, limited to cellular adaptation to altered gravity environments, from others in the field, and including some of our work using the clinostat and from spaceflight experiments. Finally, I report here preliminary results of experiments, carried out initially at Nagoya University's RIEM with follow-up experiments at the University of Arizona, to test the applicability of PC12 cells as neuronal models in which to assess adaptation to altered gravity conditions. PC12 (phaeochromocytoma) cells were used to examine two central hypotheses. The first is that the ubiquity of the cytoskeletally tethered nucleus of cells serves as a general gravisensing device which may be incidental to its other, more central genomic control-role. The second hypothesis is that the clinostat is a useful, earthbound platform on which to carry out space-biology relevant experiments in preparation for testing in space flights. PC12 cells were triggered to differentiate, into neuron-like cells, by the addition of Nerve Growth Factor (NGF) to the culture medium within 4-6 hours after cell plating and just before mounting cultures on the clinostat and control devices. Cultures, in 60 mm or 35 mm polylysine-coated dishes, were subjected to clinorotation, centrifugal force, motional controls and shear-turbulence control conditions for varying periods. Experiments were carried out at 37 degrees C. Cell morphology (including neurite characteristics) and gene activation were examined. Cytoskeletal integrity was assessed from the staining of tubulin and actin filaments. Confocal microscopy in combination with fluorescence monitoring was undertaken. At this point of the investigation, only preliminary data can be presented. This is due to various technical problems and the need to carry out rigorous statistical tests. Still, the preliminary data are of interest because they form the foundation for interpretation against the background of cellular gravisensing and adaptation to gravitational perturbations.

Actins↗
PubMed1999

[Changes of blood circulation, muscle and skeletal systems in 30 d tail-suspended [correction of tail-suspented] rats].

OBJECTIVE: To confirm the tail-suspended rat model for the study of countermeasures against weightlessness. METHOD: The changes of blood circulation, muscle and skeletal systems in control group rats (n = 15) and 30 d tail-suspended rats (n = 15) were compared. RESULT: Compared with the control group, the hemorrheology and erythrocyte deformability decreased significantly, muscle-fiber atrophy, muscle contraction function decreased, the type I muscle fibers transformed to the type II muscle fibers, bone-mineral content of L3 and load capacity of femur declined, bone metabolism changed in the suspended rats. CONCLUSION: The tail-suspended rat is a suitable animal model for the study of countermeasures against weightlessness.

Animals↗
PubMed1996

[The suspension device for hindlimb unloading in the rat--results of a video monitoring study].

Several physiological modifications reported in rats after spaceflight have been shown to be mimicked by an experimental procedure which permits skeletal unloading of the animal. Therefore, the model of hindlimb suspension is used by many authors interested in spaceflight and in hypokinesia studies. The aim of our work was to describe this model and propose a new device for headdown suspension and hindlimb unloading purposes. Using a video monitoring system, we observed that animals adapt to their new situation. Indeed, we have verified that the apparatus allows most of animals' functions. The growth curve which was not significantly modified, confirmed the present observations showing that rat feeding activity seems to not be altered. The rat is also able to move in the cage, to rest and sleep, to groom. Moreover, most of problems encountered during previous experiments have been understood and a new device with the same principles, but protected against disfunction, is proposed.

Animals↗
PubMed1999

Can centrifugation at increased G be used to predict results of 0G?

Can physiologic research on the effects of weightlessness be conducted using a centrifuge providing an increased G environment? The answer to this question, if affirmative can have extraordinary implications regarding physiologic research in space that now begs the answer to the more general and basic question, what is the 'best environment' to differentiate the biological effects of mass from weight? In considering the best environment, there are several important factors in support of conducting human and animal physiologic 'gravitational' research on centrifuges here on Earth. Increased G research using a centrifuge can be conducted for a small fraction of the cost of research in space. It can be made available to more scientists as the number of centrifuges for this type of research increases. There are far less-detailed and therefore much easier preparation requirements for animal and human studies on a centrifuge compared with space research.

Acceleration↗
PubMed1999

Angiotensin-(1-7) antagonist [D-Ala7-Ang-(1-7);A-779] attenuates post-suspension hypotension in Sprague-Dawley rats.

Cardiovascular deconditioning manifested by reduction in mean arterial pressure (MAP) and cardioaccleration are usually observed in astronauts during standing postflight. The head-down tilt (HDT) rat model with "unloaded" hindlimbs has been extensively studied because some of the observed responses mimic observations made during exposure to microgravity. Angiotensin-(1-7) is a biologically active component of the renin-angiotensin system that acts to oppose the pressor and proliferative actions of Angiotensin II. It produces a hypotensive response by either stimulating production of vasodilator prostaglandins (i.e., prostacyclin), increasing nitric oxide or both. In the present study, we have evaluated the role of a specific inhibitor of Ang-(1-7), D-Ala7-Ang-(1-7)[A-779], as a countermeasure against post-suspension hypotension.

Angiotensin II↗
PubMed1999

The effect of microgravity on proton permeability of thylakoid membranes and contribution of II and I photosystems in photosynthetic electron transport in pea chloroplasts.

According to a number investigations microgravity conditions affect membrane apparatus of photosynthesis in cells of higher plants and alga [for review, see Kordyum et al., 1994; Kordyum, 1997]. (see for review). Chloroplasts of space-grown pea plants showed disintegration of grana, shrinkage of the membrane constituting the grana stacks and other structural perturbance of the photosynthetic membranes. However there have been no studies on the effect of microgravity on proton permeability of thylakoid membranes and closely connected with this parameter their photochemical characteristics. The aim of the study is investigation of microgravity effects on protonic permeability of photosynthetic membrane and contribution of photosystem II (PSII) and photosystem I (PSI) in electron transfer from water to potassium ferrycianide (FeCy) in isolated pea chloroplasts. Pea.

Chloroplasts↗
PubMed1999

Changes in body fluid distribution during 7 days 6 degrees head-down bed rest.

It is well known that, in a state of weightlessness, body fluids shift toward the head site, but the actual rates of the migration of fluids has never been measured. In order to identify the causes of reduced orthostatic tolerance and the reduction in circulating blood volume after returning from a space mission, it is necessary to measure the changes in body fluid distribution. Although the methods for measuring changes in body fluids include the use of isotopes or pigments, such methods cannot be employed in space due to their invasive properties. Therefore, we directed our attention toward the impedance method, for which we developed a non-invasive apparatus for measuring the distribution of body fluids. We therefore measured the actual distribution of body fluids using the bed-rest method, a model of the zero gravity state.

Abdomen↗
PubMed1999

Gravity-dependent modulation of Ia afferent in human.

Recent work has shown that the H-reflex excitability of the human soleus motoneurones is modulated in reduced gravity and accompanied by a corresponding change in electromyographic (EMG) activity during space flight mission or different gravitational load. Spinal reflexes are often viewed as stereotyped motor patterns with limited scope for modification. However, recent evidence suggests that even short-latency, largely monosynaptic reflexes show a high degree of modulation during simple human motor activities such as walking and standing, and that the pattern of modulation can be specifically altered for the different functional requirements of each activity. Capady and Stein have demonstrated that H-reflex amplitude of the soleus increases progressively during the stance phase and reaches its peak amplitude late in the stance phase during walking. However, during running, the H-reflex is found to be significantly smaller than during walking, suggestion a modified spinal reflex gain for the different functional requirements of the motor behaviors. It is well documented that gravitational loads on the human body, spinal cords are much higher during standing in the water than standing in land. Little is known about the occurrence and influence of neural modulation in spinal cord during different gravitational load, which was not induced by posture but by voluntary background activity. The purpose of the present study was consequently to investigate how to effect is controlled H-reflex modulated during reduced gravity standing in a water in normal subjects.

Adult↗
PubMed1999

Development of the aortic baroreflex system under conditions of microgravity.

The mechanism of autonomic regulation of the cardiovascular system develops postnatally like as various functions of the somatic system in the mammal including human. Normal development of the mechanisms is undoubtedly fundamental for maturation of individual. Therefore it is one of important problems to be urgently solved for the human life in the coming space era to understand the process of development of the regulation mechanism of the blood circulation in the growing animal in space. We have studied ontogenesis of the aortic baroreflex in the rabbit and rat to clarify the development process of the autonomic regulation of the cardiovascular system, and found the following facts. 1) Myelinated fibers of the aortic nerve which is the afferent of the reflex continue to increase in number, thickness of myelin and the diameter of axon after birth. 2) In the rabbit the increase of the number of myelinated fibers correlates lineally with the age related increase of the basal mean arterial pressure which is probably caused by in part increases of cardiac output accompanied with the growth of body. 3) Response of the integrated activity of the aortic nerve to increases in arterial pressure is smaller in the young rat and rabbit than in the mature animals. 4) Bradycardia response of the aortic baroreflex is less or slower in the young rabbit than in the mature animal. 5) The composition of the aortic nerve in both animals and bradycardia response in the rabbit become the mature type around eight weeks of age. On the basis of the background of these evidences we have investigated the effect of microgravity on the development of the aortic baroreflex system. The following is the outlines of our investigation.

Animals↗
PubMed1999

Plasma myostatin-immunoreactive protein is increased after prolonged bed rest with low-dose T3 administration.

It has been hypothesized that myostatin, a newly identified member of the transforming growth factor-beta (TGF-beta) family of proteins, acts as a negative regulator of skeletal muscle growth. Because bed rest induced muscle atrophy results from a decreased rate of muscle protein synthesis, we hypothesized that circulating levels of myostatin would be increased following prolonged bed rest. Twelve men (age, 35.8 +/- 4.6 yr; height, 175.7 +/- 2.3 cm; weight, 74.8 +/- 3.5 kg; mean +/- SE) were confined to bed for 25 days at 6 degrees head-down tilt while receiving triiodothyronine (T3; 50 micrograms/day) to accelerate protein loss. Total lean body and appendicular skeletal muscle mass were determined by dual energy x-ray absorptiometry (DEXA) before and after the bed rest period. Plasma myostatin-immunoreactive protein was measured in blood samples obtained after an overnight fast 5 days prior to, and on the 25th day of bed rest. Lean body mass decreased an average 2.2 kg (p < 0.0001). Appendicular skeletal muscle accounted for a majority of the lean body mass loss. On day 25 of bed rest, plasma myostatin-immunoreactive protein was 12% higher (p = 0.01) than measured at baseline. These data support the idea that myostatin regulates muscle growth in humans and that it may be a novel target for interventions aiming to reduce space flight induced muscle atrophy.

Adult↗
PubMed1998

[Effect of -6 degrees bed-rest on T-lymphocyte proliferation and cytokines production in human].

In this study, the effect of -6 degrees head-down bed-rest on proliferation of T lymphocyte stimulated by phytohemagglutinin, a kind of polyclone T cell activators and cytokines production were observed. The results showed: after 2 d bed-rest, proliferation of T lymphocyte stimulated by phytohemagglutinin decreased significantly; the activity of interleukin-2 trended to decrease; the expression of interleukin-2 receptor tended to increase; the production of interleukin-6 decreased significantly. After 6 d bed-rest, T lymphocyte proliferation restored to normal; the activity of interleukin-2 and expression of interleukin-2 receptor had no change; the production of interleukin-6 decreased significantly. This result demonstrated that -6 degrees bed-rest can decrease T lymphocyte proliferation function, and this decrease may be caused by the reduction of cytokines secretion.

Adult↗
PubMed1998

[Changes in cerebral circulation function during head down bed rest for 7 days].

To further understand the effects and regulation of brain circulation before, during and after short-term -6 degrees head down bed rest (HDT), 6 healthy young men aged 19-21 years, were subjected to HDT for 7 d. Cerebral blood flow velocity in the middle cerebral arteries of both sides was measured with a TC2000TCD instrument in 6 young adults before, during, and after 7d HDT. The results showed that cerebral blood flow velocity in the middle cerebral arteries increased throughout HDT, the increase was obvious in 24 h. They reached the highest value at the 4th hour and the lowest value on the 5 th day, and then, there were a tendency to rise on the 6th day and 7th day. The changes were about the same on both sides.

Adult↗
PubMed1998

[Changes of bone cytokines and compensating regulation in tail suspended rats].

The aim of the study was to determine the relationship between the changes in bone metabolism and insulin-like growth factor--I(IGF-I) as well as epidermal growth factor (EGF). 10 Male S.D. rats were tail-suspended for 28 d with another 10 free active rats as control. The results showed that mineral content increased significantly, osteocalcin and albumin content had no significant change, but IGF-I and EGF content increased significantly in L3 in the suspended rats. The results suggest that although there are no change in osteocalcin and albumin content, the phenomenon of bone mineral loss still exists in the suspended rats. The increase in IGF-I and EGF content may be one of the compensation responses of the bone in the suspended rats.

Animals↗
PubMed1998

[Noninvasive evaluation of cardiovascular autonomic regulation and its application in physiological studies under weightlessness].

Recent progress in the noninvasive evaluation methods of cardiovascular autonomic regulation, including autonomic function tests, baroreflex function assessment, and heart rate, blood pressure variability analysis were discussed, and the results of applying these methods in physiological studies on head-down bed rest, head-up tilt, lower body negative pressure and aerobic training were reported. It suggests that noninvasive evaluation methods of cardiovascular autonomic regulation are effective means in weightlessness physiology study.

Aerospace Medicine↗