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At least 235 records · Page 13

Fluid and electrolyte homeostasis in space - A primate model to look at mechanisms

To elucidate the physiological mechanisms involved in the cardiovascular and renal responses to spaceflight, a ground-based primate model has been developed which uses lower body positive pressure (LBPP) to simulate the chronic central vascular expansion associated with weightlessnes. Four male squirrel monkeys with chronically implanted arterial and venous catheters and the capacity for continuous urine collection were subjected to LBPP for 4 days. Onset of LBPP resulted in an immediate diuresis, natriuresis and kaliuresis and a significant fall in plasma aldosterone and potassium levels. By day 2 the level of natriuresis had decreased by half, while potassium excretion and plasma aldosterone values had returned to control levels despite the persistence of a significantly reduced plasma potassium concentration. It is concluded that the low plasma potassium level appears not to stimulate a compensatory fall in plasma aldosterone because of the simultaneous presence of body volume contraction acting to raise aldosterone levels.

Moore-Ede, M. C.↗

Extensions of suspension systems to measure effects of hypokinesia/hypodynamia and antiorthostasis in rats

Suspension systems are used to simulate hypokinetic/hypodynamic (H/H) and anitorthostatic (AO) responses seen under conditions of weightlessness. Growing rats in H/H suspension with unloaded hindlimbs for one and two weeks respond with muscle atrophy and increased excretion of nitrogenous end products such as urea, NH3 and 3 methyl histidine. Since muscle is in a dynamic state of synthesis and breakdown of protein, relationships between protein, RNA and DNA contents in the four muscles which reflect weight bearing and non-weight bearing functions were assessed. Protein and RNA progressively decreased over a one and two week period of H/H suspension: soleus gastrocnemius=plantaris EDL. Concommitant analysis of DNA contents showed there were no changes. The interpretation was that protein synthesis was slowed during H/H. As with muscle mass, protein and RNA levels recovered rapidly after removal from H/H. The AO rats (which are also H/H) respond with diuresis, natriuresis and kaliuresis in a manner comparable to responses seen when thoracic blood vessels are volume loaded.

Musacchia, X. J.↗

Current concepts of space flight induced changes in hormonal control of fluid and electrolyte metabolism

A systematic analysis of body fluid and renal dynamics during simulated space flight (head-down bedrest) was undertaken to increase understanding of the physiologic effects of acute cephalad fluid shifts. The earliest effects were increases in central venous pressure and decreases in plasma aldosterone, epinephrine and norepinephrine and glomerular filtration rate, 2 h after the beginning of bedrest. Decreases in plasma angiotensin I at 6 h may have resulted from the increased effective pressure and decreased sympathetic activity seen earlier in bedrest. The early decrease in aldosterone and ADH is thought to contribute to an increase, by 6 h, in urinary excretion of salt and water. Fluid and electrolyte losses occur during space flight, and analysis of body fluids from Space Shuttle crewmembers has indicated that conservation of these substances is begun almost immediately upon cessation of weightlessness. Operational medicine measures to counteract dehydration and electrolyte loss resulted in a less extreme physiologic response to the flight.

Leach, C. S.↗

The validity of an animal model for experiments related to weightlessness

Animal evolution has witnessed morphological and physiological adaptations to gravitational forces. In the rat, hind limb muscles can be used to illustrate a range of load bearing functions: soleus - gastrocnemius = plantaris - extensor digitorum longus (EDL). A harness suspension apparatus is used to induce hypokinesia and hypodynamia (H&H) and to simulate responses comparable to those seen in weightlessness (i.e., COSMOS experiments). After one and two weeks of suspension H&H, there is muscle atrophy with a loss in muscle mass; the result of loss in muscle protein. Concommitantly, there is a decrease in RNA, but not in DNA content. The effects are greatest in the soleus and least in the EDL. These recent findings, in concert with earlier reports of increased nitrogenous excretion, suggest that both decreased protein synthesis and increased protein catabolism are characteristic of muscle atrophy. Recovery is seen in terms of reversal of these effects after removal from suspension.

Musacchia, X. J.↗

Vasopressin release induced by water deprivation - Effects of centrally administered saralasin

Uncertainty exists as to whether endogenous angiotensin activates brain mechanisms controlling vasopressin (AVP) secretion during dehydration. Various doses of saralasin were injected into a lateral cgrebroventricle (IVT) of conscious, male rats deprived of water for 48 h. The rats were killed at different times. The concentration of AVP in the plasma p(AVP), measured by radioimmunoassay, was unaffected by saralasin. IVT pretreatment with 1-Sar-8-Ile-angiotensin II blocked maximal AVP release by IVT angiotensin, but this pretreatment did not reduce p(AVP) after 24, 48 or 72 hr water deprivation. A 3-hour continuous IVT infusion of CSF or saralasin (10 micrograms/hour) into 48-hour water-deprived rats revealed equivalent p(AVP) concentration and urine volumes. When the infusions were continued for 3 h more with water available, control and saralasin-treated rats: (1) drank at similar rates, (2) excreted similar amounts of urine, and (3) reduced their p(AVP) concentration levels to the same extent. IVT saralasin did not affect p(AVP) concentration of rats dehydrated with hypertonic NaCl. Combined IVT saralasin and atropine reduced p(AVP) concentration of 48-hour water deprived rats about 30 percent (p less than 0.05). It is concluded that redundancy exists for sensing, integrating and releasing vasopressin in dehydrated rats.

Keil, L. C.↗

A suspension model for hypokinetic/hypodynamic and antiorthostatic responses in the mouse

Hypokinetic/hypodynamic and antiorthostatic responses to weightlessness and bedrest were simulated in mice using a suspension technique. Animals were suspended for 1 or 2 weeks in an antiorthostatic posture and positioned to permit freedom of movement but eliminate load bearing by the hindlimbs. Suspended mice exhibited reduced food and water intakes and a rapid 10 percent decrease in body weight to a level which was maintained for the remainder of the suspension period. Diuresis was evident in suspended mice, but the natriuresis and kaliuresis previously observed in the suspended rat were not evident. Differential hindlimb muscle atrophy and increased excretion of urea and ammonia were also noted in suspended mice. Postsuspension recovery studies indicated that the recovery process was highly effective. These results document specific responses in the mouse and similarities in the responses of mice and rats to suspension. These studies expand the utility of the suspension model and suggest that the mouse may be useful in future studies simulating both weightlessness and bedrest.

Steffen, J. M.↗

Immersion diuresis without expected suppression of vasopressin

There is a shift of blood from the lower parts of the body to the thoracic circulation during bed rest, water immersion, and presumably during weightlessness. On earth, this central fluid shift is associated with a profound diuresis. However, the mechanism involved is not yet well understood. The present investigation is concerned with measurements regarding the plasma vasopressin, fluid, electrolyte, and plasma renin activity (PRA) responses in subjects with normal preimmersion plasma vasopressin (PVP) concentration. In the conducted experiments, PRA was suppressed significantly at 30 min of immersion and had declined by 74 percent by the end of the experiment. On the basis of previously obtained results, it appears that sodium excretion during immersion may be independent of aldosterone action. Experimental results indicate that PVP is not suppressed by water immersion in normally hydrated subjects and that other factors may be responsible for the diuresis.

Keil, L. C.↗

Blood Pressure Responses and Mineral Ocorticoid Levels in the Suspended Rat Model for Weightlessness

Cardiovascular responses and fluid/electrolyte shifts seen during space flight are attributed to cephalad redistribution of vascular fluid. The antiorthostatic (AO) rat (suspended head down tilted, 15-20 deg) is used to model these responses. Current studies show that elevated blood pressures in A0 rats are sustained for periods up to seven days. Comparisons are made with presuspension rats. Increased blood pressure in head down tilted subjects suggests a specific response to A0 positioning, potentially relatable to cephalad fluid shift. To assess a role for hormonal regulation of sodium excretion, serum aldosterone levels were measured.

Musacchia, X. J.↗

The behavior of renal-regulating hormones during hypogravic stress

The regulation of fluid and electrolyte behavior during space flight is believed to be under control, in large part, of a group of hormones which have their major effects on renal excretion. The hormones studied include renin-angitensin, aldosterone, and antidiuretic hormone (ADH). The regulatory systems of these renal-regulating hormones as they act individually and in concert with each other are analyzed. The analysis is based on simulations of the mathematical model of Guyton. A generalized theory is described which accounts for both short-term and long-term behavior of this set of hormones.

Leonard, J. I.↗

A Brief Description of the Two Primate Experiments to Be Carried Out on SL-4

Two primate experiments to be carried on Spacelab 4 are discussed. One of these investigates thermoregulation of primates during altered gravity. In previous ground-based tests, primate heat distribution was shown to change during centrifugation (a way of subjecting subjects to higher-than-Earth gravity), the inner body cooling off and the skin temperature rising. The adaptive and homeostatic mechanisms triggered by spaceflight are studied. Ways in which to correct any undesirable shifts in the homeostatic capabilities of the thermoregulatory control system are addressed. The other experiment involving primates addressess the changes in fluid distribution and electrolyte content of blood that occur in spaceflight. During previous space missions, fluid shifts from the legs to the chest and head have been noted. Ground-based studies have shown decreases in blood potassium levels and increases in potassium excretion.

Elsea, L.↗

Space-flight simulations of calcium metabolism using a mathematical model of calcium regulation

The results of a series of simulation studies of calcium matabolic changes which have been recorded during human exposure to bed rest and space flight are presented. Space flight and bed rest data demonstrate losses of total body calcium during exposure to hypogravic environments. These losses are evidenced by higher than normal rates of urine calcium excretion and by negative calcium balances. In addition, intestinal absorption rates and bone mineral content are assumed to decrease. The bed rest and space flight simulations were executed on a mathematical model of the calcium metabolic system. The purpose of the simulations is to theoretically test hypotheses and predict system responses which are occurring during given experimental stresses. In this case, hypogravity occurs through the comparison of simulation and experimental data and through the analysis of model structure and system responses. The model reliably simulates the responses of selected bed rest and space flight parameters. When experimental data are available, the simulated skeletal responses and regulatory factors involved in the responses agree with space flight data collected on rodents. In addition, areas within the model that need improvement are identified.

Brand, S. N.↗

Atrophy and growth failure of rat hindlimb muscles in tail-cast suspension

The primary objective of the present study is related to an evaluation of a modified tail-cast suspension model as a means of identifying metabolic factors which control or are associated with muscle atrophy and growth failure. Two different control conditions (normal and tail-casted weight bearing) were studied to determine the appropriate control for tail-cast suspension. A description is presented of a model which is most useful for studying atrophy of hindlimb muscles under certain conditions. Female Sprague-Dawley rats were employed in the experiments. Attention is given to growth rate and urinary excretion of urea and ammonia in different types of rats, the relationship between body weight and skeletal muscle weight, and the relationship between animal body weight and rates of protein synthesis and protein degradation.

Jaspers, S. R.↗

Mechanism for negative water balance during weightlessness An hypothesis

The mechanism for the apparent decrease in body fluid volume in astronauts during spaceflight remains obscure. The widespread postulate that the hypohydration is the result of the Henry-Gauer reflex, a diuresis caused by inhibition of vasopressin secretion resulting from increased left and perhaps right atrial (central) venous pressure, has not been established with direct measurements on astronauts. An hypothesis is proposed to account for fluid-electrolyte shifts during weightlessness. A moderate but transient increase in central venous pressure occurs when orbit is entered that is insufficient to activate the Henry-Gauer reflex but sufficient to stimulate the release of atrial natriuretic peptides. Increased sodium excretion would facilitate some increased urinary water loss. The resulting relatively dilute plasma and interstitial fluids would cause fluid to shift into the cellular space, resulting in edema in the head and trunk and inhibition of thirst and drinking. Thus, the negative water balance in astronauts would be caused by a gradual natriuresis and diuresis coupled with reduced fluid intake.

Greenleaf, J. E.↗

Plasma aldosterone and sweat sodium concentrations after exercise and heat acclimation

The relationship between plasma aldosterone levels and sweat sodium excretion after chronic exercise and heat acclimation was investigated, using subjects exercised, at 40 C and 45 percent humidity, for 2 h/day on ten consecutive days at 45 percent of their maximal oxygen uptake. The data indicate that, following heat acclimation, plasma aldosterone concentrations decrease, and that the eccrine gland responsiveness to aldosterone, as represented by sweat sodium reabsorption, may be augmented through exercise and heat acclimation.

Kirby, C. R.↗

Regulation of calcium metabolism during prolonged antiorthostatic hypokinesia

Characteristics of the regulation of calcium exchange in healthy persons exposed to 182 days of antiorthostatic hypokinesia are investigated. Total calcium concentrations, ionized calcium activities and parathyroid hormone concentrations in blood serum were determined, before, during, and up to 15 days after a 182-day period of strict bed rest at a head down tilt of 4 deg; and tests of blood urine responses to a calcium lactate stress were performed to study the role of the kidneys. An increase in calcium ion activity is observed during the period of hypokinesia, while total calcium concentrations changed to a lesser degree. Plasma parathyroid hormone levels are found to significantly exceed background levels during hypokinesia and in the recovery period immediately following. Finally, the increase in calcium excretion in the urine during prolonged limitations of muscular activity is found to be connected with both an enhancement of calcium filtration and a decrease in its reabsorption in the kidneys, possibly due to changes in hormonal regulation.

Grigoryev, A. I.↗

Fluid control mechanisms in weightlessness

Experiments performed on Space Shuttle flights have emphasized study of the earliest effects of the cephalad fluid shift resulting from microgravity. Analysis of one subject's urine collected during flight showed that a sharp increase in antidiuretic hormone occurred within 2 h of launch, followed by an increase in cortisol excretion. Although this subject had symptoms of the space adaptation syndrome (SAS), inflight data from Spacelab missions suggested that these transient changes were not caused by SAS. Unpaired t-tests and Mann-Whitney tests showed that before and after flight, plasma thyroxine and urine osmolality were significantly higher in Shuttle crewmembers who exhibited more severe symptoms of SAS than in asymptomatic crewmembers.

Leach, Carolyn S.↗

The endocrine system in space flight

A trial natriuretic factor (ANF), a hormone recently shown to regulate sodium and water excretion, has been measured in blood specimens obtained during flight. After 30 or 42 h of weightlessness, mean ANF was elevated. After 175 or 180 h, ANF has increased by 59 percent, and it changed little between that time and soon after landing. There is probably an increase in ANF early inflight associated with the fluid shift, followed by a compensatory decrease in blood volume. Increased renal blood flow may cause the later ANF decrease. Erythropoietin (Ep), a hormone involved in the control of red blood cell proudction, was measured in blood samples taken during the first Spacelab mission and was significantly decreased on the second day of flight, suggesting also an increase in renal blood flow. Spacelab-2 investigators report that the active vitamin D metabolite 1 alpha, 25-dihydroxyvitamin D-3 increased early in the flight, indicating that a stimulus for increased bone resorption occurs by 30 h after launch.

Leach, C. S.↗

Maladjustment of kidneys to microgravity: Design of measures to reduce the loss of calcium

Losses of skeletal calcium and body fluids occur during prolonged exposure to microgravity. The kidney plays a major role in regulating the physiological functions involved. Relative to this regulatory function, the kidney performs three operations: filtration of blood plasma through the glomeruli, reabsorption, and secretion of fluid and electrolytes so that needed components are retained and only waste is eliminated in the urine. Using data published in Biomedical Results from Skylab, researchers performed new calculations that reflect more directly the operations of the kidney in the handling of calcium, sodium, chloride, potassium and phosphate during space flight. These calculations revealed that the fraction of filtered calcium that was rejected by renal tubules and excreted in the urine increased by 71 percent, from 1.77 percent (preflight) to 3.02 percent (inflight) of the filtered load. This represents a large absolute increase because the total filtered amount is huge. Because the tubular rejection fraction of other ions increased relatively less than that of calcium, researchers postulate the inflight development of a specific renal defect that causes an excessive loss of calcium in urine and thereby contributes to the weakening of bones.

Nechay, Bohdan R.↗