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Musacchia, X. J.

Publications and source records attributed to Musacchia, X. J..

At least 37 records · Page 2

The use of suspension models and comparison with true weightlessness

A resume is presented of various papers concerning the effect of weightlessness on particular physiological and biochemical phenomena in animal model systems. Findings from weightlessness experiments on earth using suspension models are compared with results of experiments in orbit. The biological phenomena considered include muscle atrophy, changes in the endocrine system, reduction in bone formation, and changes in the cardiovascular system.

Musacchia, X. J.↗

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.↗

Fatigue and contraction of slow and fast muscles in hypokinetic/hypodynamic rats

The effects of hypokinesia/hypodynamia (H/H) on the fatigability and contractile properties of the rat soleus (S) and gastrocnemius (G) muscles have been investigated experimentally. Whole body suspension for one week was used to induce H/H, and fatigue was brought on by train stimulation for periods of 45 and 16 minutes. Following stimulation, rapid rates of fatigue were observed in the G-muscles of the suspended rats, while minimal fatigue was observed in the S-muscles. The twitch and tetanic contractile properties of the muscles were measured before and after train stimulation. It is found that H/H suspension increased twitch tension in the G-muscles, but did not change any contractile properties in the S-muscles. The peak twitch, train, tetanic tensions and time to peak were unchanged in the S-muscles of the suspended rats. On the basis of the experimental results, it is concluded that 1 wk of muscle atropy induced by H/H significantly increases fatigability in G-muscles, but does not affect the contractile properties of fast-twitch and slow-twitch muscles.

Fell, R. D.↗

Thymic involution in the suspended rat model for weightlessness - Decreased glucocorticoid receptor concentration

Hindlimb muscle atrophy, thymic involution and adrenal hypertrophy in rats during spaceflight can be simulated using suspension models. Skeletal muscle and thymus are sensitive to gluco-corticoids (GC), and previous studies have demonstrated that muscle atrophy in suspended rats is associated with increased GC receptor concentration. The objectives were to confirm thymic involution during suspension, and determine if involution correlated with increased GC receptor concentration. Seven days of antiorthostatic (AO) suspension of rats produced a significant (P less than 0.001) reduction in thymic wet weight not associated with an alteration of percent water content. GC receptor concentration (pmol/mg protein) decreased 20 percent (P less than 0.025) in thymus glands from 7 day AO suspended rats. Suspension, therefore, is associated with involution of the thymus, but this is not dependent upon AO positioning. Thymus GC receptor concentrations were depressed in 7-day suspended rats, in contrast with previous observations on skeletal muscle, suggesting that different mechanisms may underlie these responses.

Steffen, J. M.↗

Cardiovascular and hormonal (aldosterone) responses in a rat model which mimics responses to weightlessness

Cardiovascular responses and fluid/electrolyte shifts seen during spaceflight have been attributed to cephalad redistribution of vascular fluid. The antiorthostatic (AO) rat (suspended, head-down tilt of 15-20 deg) is used to model these responses. This study documents that elevated blood pressures in AO rats are sustained for periods of up to seven days, compared with presuspension values. Increased blood pressures in AO rats suggests a specific response to AO positioning, potentially relatable to a cephalad fluid shift. To assess a role for hormonal regulation of sodium excretion, serum aldosterone levels were measured. Circulating aldosterone concentrations were seen to increase approximately 100 percent during seven days of AO suspension, concurrently with a pronounced natriuresis. These results suggest that aldosterone may not be involved in the long term regulation of increased Na(+) excretion in AO animals. These studies continue to show the usefulness of models for the development of animal protocols for space flight.

Musacchia, X. J.↗

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.↗

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.↗

Effect of antiorthostatic suspension on interferon-alpha/beta production by the mouse (41939)

Mice were suspended in a model that simulates the weightlessness that occurs during prolonged space flight. After one and two weeks of suspension in an antiorthostatic (head-down tilt) position, the mice were challenged with polyriboinosinic-polyribocytidylic acid to induce interferon-alpha/beta. Interferon production was severely reduced in mice that had been suspended. When mice were allowed to recover in cages for a week following removal from suspension, they recovered their full interferon-production capacity. Mice suspended in an orthostatic (horizontal) position did not have their interferon production capabilities affected, which indicates that stress per se was not a major component in the effects of antiorthostatic suspension on interferon induction.

Rose, Andrea↗

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.↗

Rat hindlimb muscle responses to suspension hypokinesia/hypodynamia

Hypokinetic/hyupodynamic (H/H) whole body suspension of rats eliminates hindlimb load bearing functions while permitting continued use of the forelimbs. Responses of hindlimb muscles were assessed in terms of absolute and relative weights during 1 and 2 weeks of H/H suspension. Muscle mass loss was in the order soleus greater than gastrocnemius equal to plantaris greater than extensor digitorum longus (EDL). The soleus, a postural antigravity muscle composed mainly of slow twitch fibers, was most sensitive, losing 35 and 45 percent of its weight during the first and second weeks, respectively. The gastrocnemius and plantaris showed losses during the first week but no significant loss during the second wee. The EDL showed little or no weight loss. During post suspension recovery all muscles showed a weight gain. H/H suspended rats failed to grow; following removal from suspension they gained weight linearly, comparable to controls. Products of muscle metabolism including urea, ammonia, and 3-methylhistidine increased in the urine during H/H suspension and were significantly reduced approaching control levels during recovery. This suspension model offers considerable promise for comparison with H/H responses during weightlessness.

Musacchia, X. J.↗

Effect of suspension hypokinesia/hypodynamia on glucocorticoid receptor levels in rat hindlimb muscles

Ilyina-Kakueva et. al. (1976) conducted an investigation in which rats were exposed to weightlessness during the Cosmos program. An examination of the rats revealed a marked atrophy of hindlimb muscles. A suspension model has been developed to simulate these weightlessness-induced alterations. In agreement with the Cosmos studies, suspension hypokinesia/hypodynamia (H/H) results in differential atrophy of hindlimb muscles in rats. Recent studies have demonstrated elevated glucocorticoid receptor numbers in the gastrocnemius muscle following immobilization and denervation. One of the objectives of the present investigation was to evaluate the effect of suspension H/H on glucocorticoid receptor levels in rat hindlimb muscles. Another objective was to ascertain whether altered receptor levels reflect the differential nature of hindlimb muscle atrophy during suspension H/H. The obtained findings suggest that differential muscle atrophy resulting from H/H may result from differential alterations of glucocorticoid receptor levels.

Steffen, J. M.↗

Short term /1 and 3 day/ cardiovascular adjustments to suspension antiorthostasis in rats

Antiorthostasis (AO) results in responses reflective of thoracic vessel loading. Initial findings included fluid and electrolyte shifts (diuresis and natriuresis) in AO but not in orthostatic (O) rats. This study aims at obtaining supportive evidence for cardiovascular responses, E.g., blood pressure and related parameters, in light of the original hypothesis. Tilting rats rapidly head-up from either horizontal (O) or head-down (AO) positions was used to assess cardiovascular sensitivities. O and AO rats were used after 1 or 3 days of suspension. Rats were controls (C), pre-tilted O and AO, tilted O and AO (rapid head-up 70-80 deg); post-tilted (to original postures). MAP in C rats was 108 +2 mmHg, in O, (117 + or - 1.02) and AO, (120 + or - 0.58). MAP, diastolic pressure (DP) and pulse pressure were consistently elevated in AO rats on day 3. With rapid head-up tilt, only MAP and DP showed significant increases. These changes were seen as cardiovascular responses to AO and support further use of this rat model for AO studies.

Musacchia, X. J.↗

A new rat model for studies of hypokinesia and antiorthostasis

A new rat model (suspension and immobilization) is described for induction of hypokinesia and orthostatic manipulations. Hypokinetic responses were comparable to those in prolonged bed rest and weightlessness in humans, body or limb casted and small cage restrained animals. Responses to antiorthostasis (15 to 20 deg head down tilt) in rats were similar to those in neutral bouyancy tests in humans and animals and to those in prolonged bed rest in humans. During seven days of hypokinesia there was an atrophy of the gastrocnemius and increased excretion of urinary nitrogeneous end products. The antiorthostatic (AOH) 15 to 20 deg head down tilt resulted in diuresis, natriuresis and kaliuresis. No comparable responses were observed in orthostatic hypokinetic (OH) rats. Readaptation from AOH and OH occurred during one week recovery in metabolic cage conditions.

Musacchia, X. J.↗

Suspension restraint - Induced hypokinesia and antiorthostasis as a simulation of weightlessness

Muscle, renal, fluid and electrolyte responses were measured in suspended rats; the hind limbs are non-load bearing and the front limbs can be used for feeding and grooming. Hind limb hypokinesia reverses after removal from the suspension harness. This suspension system is adjustable for a head-down tilt to produce antiorthostatic responses which are also reversible. Responses to hypokinesia or antiorthostatic hypokinesia for up to 14 days were measured, e.g., muscle atrophy: soleus greater than gastrocnemius equals plantaris greater than extensor digitorum longus, kaliuresis, and increased excretion of urea, NH3, and 3 methylhistidine. Muscle protein loss, a response to a reduction in RNA, is also reversible. A head-down tilt for 7-14 days results in diuresis and natriuresis. These changes are reversed within 24 hours after removal from the restraint harness. Physiological effects of suspension restraint can be used to simulate and predict responses to microgravity exposure.

Musacchia, X. J.↗

Model for antiorthostatic hypokinesia - Head-down tilt effects on water and salt excretion

Water and electrolyte excretion was investigated in antiorthostatic hypokinetic and orthostatic hypokinetic and control rats in metabolic cages. Significant (t test, P less than 0.05) diuresis, natriuresis, and kaliuresis occurred in the antiorthostatic hypokinetic subjects but did not occur in either the orthostatic hypokinetic or controls. Recovery from antiorthostatic hypokinesia was characterized by retention of water, sodium, and potassium. Patterns of changes in body weight and food and water consumption were virtually identical in antiorthostatic and orthostatic hypokinetic rats and thus could not account for the differences in renal handling of water and electrolytes. Also, differences in ingestion of food and water in controls could not account for differences in excretion of water and electrolytes between these and antiorthostatic hypokinetic rats. It was concluded that the antiorthostatic position was responsible for the diuresis and natriuresis and that the antiorthostatic hypokinetic rat appears to be a good model for the study of water and elecrolyte excretion during conditions such as bed rest, water immersion, and exposure to weightlessness.

Deavers, D. R.↗

A model for hypokinesia: Effects on muscle atrophy in the rat

Hypokinesia in the hindlimbs of rats was induced by suspension; a newly developed harness system was used. The animal was able to use its forelimbs to maneuver, within a 140 deg arc, to obtain food and water and to permit limited grooming of the forequarters. The hindlimbs were nonload bearing for 7 days; following a 7-day period of hypodynamia, selected animals were placed in metabolic cages for 7 days to study recovery from hypokinesia. During the 7-day period of hypokinesia there was evidence of muscle atrophy. Gastrocnemius weight decreased, renal papillary urea content increased, and daily urinary losses of NH3 and 3-methylhistidine increased. During the 7-day recovery period muscle mass and excretion rate of urea, NH3 and 3-methylhistidine returned to control levels. Calcium balance was positive throughout the 7-day period of hypokinesia. Hypertrophy of the adrenals suggested the occurrence of some level of stress despite the apparent behavioral adjustment to the suspension harness. It was concluded that significant muscle atrophy and parallel changes in nitrogen metabolism occur in suspended rats and these changes are readily reversible.

Musacchia, X. J.↗

Intestinal transport of hexoses in the rat following chronic heat exposure

The study examines intestinal transport of sugars (D-glucose and D-galactose) in vitro and assesses organ maintenance in chronically heat-exposed rats. The results suggest that the response of intestinal absorption to heat exposure in the rat involves changes in intestinal weight and in glucose utilization. Despite the reduction in total intestinal weight, the ability of intestinal tissue to transport hexose per unit weight remains stable. Differences in intestinal weight and glucose utilization between pair-fed and heat-exposed animals suggest that the intestinal response to chronic heat exposure is not solely a function of the amount of food consumed. Alterations of hexose transport appear to be related to altered glucose metabolism and not altered transport capacity.

Carpenter, M.↗

Mechanisms responsible for decreased glomerular filtration in hibernation and hypothermia

Measurements of blood pressure, heart rate, red blood cell and plasma volumes, and relative distribution of cardiac output were made on hibernating and hypothermic adult male and female golden hamsters weighing 120-140 g to study the mechanisms underlying the elimination or marked depression of renal function in hibernation and hypothermia. The results suggest that the elimination or marked depression in renal function reported in hibernation and hypothermia may partly be explained by alterations in cardiovascular system function. Renal perfusion pressure which decreases nearly 60% in both hibernation and hypothermia and a decrease in plasma volume of roughly 35% in the hypothermic animal might both be expected to markedly alter glomerular function.

Tempel, G. E.↗