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At least 1,603 records · Page 89

Development and testing of a mouse simulated space flight model

The development and testing of a mouse model for simulating some aspects of weightlessness that occurs during space flight, and the carrying out of immunological experiments on animals undergoing space flight is examined. The mouse model developed was an antiorthostatic, hypokinetic, hypodynamic suspension model similar to one used with rats. The study was divided into two parts. The first involved determination of which immunological parameters should be observed on animals flown during space flight or studied in the suspension model. The second involved suspending mice and determining which of those immunological parameters were altered by the suspension. Rats that were actually flown in Space Shuttle SL-3 were used to test the hypotheses.

Sonnenfeld, Gerald↗

Microcirculatory fluid dynamics in weightlessness and simulated weightlessness

The method of Smith et al. (1985), which makes it possible to simultaneously measure the macrocirculation and microcirculation in an unanesthetized rat, was used to study the effect of acute hypokinesia on the rat microvascular system. The measurements yielded values of the length, diameter, and number of arteriolar and venular vessels; vascular patterns; branching ratios; and the amplitude and frequency of vasomotion. Early effects (30-60 min after the start of the head-down tilt) include a 10 percent increase in the diameter of arterioles, a slight increase of heart rate and mean arterial blood pressure, and an increase in the heart rate-pulse pressure product, with most of the changes returning to normal after 2-3 h. The baroreceptor reflex index was reduced by almost 50 percent for the first 2 h, but rebounded to almost 3 times the control value after 3 h. This indicates that, in spite of relatively small changes in gross hemodynamic parameters, the cardiovascular function is altered significantly during the acute phase of hypokinesia.

Hutchins, P. M.↗

Effect of anabolic steroids on overloaded and overloaded suspended skeletal muscle

The effect of treatment with an anabolic steroid (nandrolone decanoate) on the muscle mass, the subcellular protein content, and the myosin patterns of normal overloaded and suspended overloaded plantaris muscle in female rat was investigated, dividing rats into six groups: normal control (NC), overload (OV), OV steroid (OV-S), normal suspended (N-sus), OV suspended (OV-sus), and OV suspended steroid (OV-sus-S). Relative to control values, overload produced a sparing effect on the muscle weight of the OV-sus group as well as increases of muscle weight of the OV group; increased protein content; and an increased expression of slow myosin in both OV and OV-sus groups. Steroid treatment of OV animals did not after the response of any parameter analyzed for the OV group, but in the OV-sus group steroid treatment induced increases in muscle weight and in protein content of the OV-sus-S group. The treatment did not alter the pattern of isomyosin expression observed in the OV or the OV-sus groups. These result suggest that the steroid acts synergistically with functional overload only under conditions in which the effect of overload is minimized by suspension.

Tsika, R. W.↗

The effect of altered 5-hydroxytryptamine levels on beta-endorphin

The purpose of the present study was to examine the effect of altering the concentration of 5-hydroxytryptamine (5-HT) on beta-endorphin (beta-Ep) content in the hypothalamus, thalamus, and periaqueductal gray (PAG)-rostral pons regions of the rat brain. The selective 5-HT reuptake inhibitor, fluoxetine (10 mg/kg), significantly lowered beta-Ep content in the hypothalamus and the PAG. Parachlorophenylalanine, which inhibits 5-HT synthesis, significantly elevated beta-Ep in all brain parts studied. Intracisternal injections of the neurotoxin 5-prime, 7-prime-dihydroxytryptamine with desmethylimipramine pretreatment significantly increased beta-Ep content in the hypothalamus and the PAG. In adrenalectomized rats, fluoxetine significantly decreased beta-Ep levels in the hypothalamus and increased the levels in the PAG. The results indicate that 5-HT may modulate the levels of brain beta-Ep.

Soliman, Karam F. A.↗

Continuous flow electrophoretic separation of proteins and cells from mammalian tissues

This paper describes an apparatus for continuous flow electrophoresis (CFE), designed to separate macromolecules and cells at conditions of microgravity. In this CFE, buffer flows upward in a 120-cm long flow chamber, which is 16-cm wide x 3.0-mm thick in the microgravity version (and 6-cm wide x 1.5-mm thick in the unit-gravity laboratory version). Ovalbumin and rat serum albumin were separated in space (flight STS-4) with the same resolution of the two proteins achieved at 25 percent total w/v concentration that was obtained in the laboratory at 0.2 percent w/v concentration. Rat anterior pituitary cells, cultured human embryonic kidney cells, and canine Langerhans cells were separated into subpopulations (flight STS-8) more effectively than in unit gravity, with comparable resolution having been achieved at 100 times the concentration possible on earth.

Hymer, W. C.↗

Cleaning Animals' Cages With Little Water

Proposed freeze/thaw method for cleaning animals' cages requires little extra weight and consumes little power and water. Cleaning concept developed for maintaining experimental rat cages on extended space missions. Adaptable as well to similar use on Earth. Reduces cleaning time. Makes use of already available facilities such as refrigerator, glove box, and autoclave. Rat waste adheres to steel-wire-mesh floor of cage. Feces removed by loosening action of freezing-and-thawing process, followed by blast of air.

Harman, Benjamin J.↗

Clenbuterol, a beta(2)-agonist, retards atrophy in denervated muscles

The effects of a beta(2) agonist, clenbuterol, on the protein content as well as on the contractile strength and the muscle fiber cross-sectional area of various denervated muscles from rats were investigated. It was found that denervated soleus, anterior tibialis, and gastrocnemius muscles, but not the extensor digitorum longus, of rats treated for 2-3 weeks with clenbuterol contained 95-110 percent more protein than denervated controls. The twofold difference in the protein content of denervated solei was paralleled by similar changes in contractile strength and muscle fiber cross-sectional area.

Zeman, Richard J.↗

Slow to fast alterations in skeletal muscle fibers caused by clenbuterol, a beta(2)-receptor agonist

The effects of a beta(2)-receptor agonist, clenbuterol, and a beta(2) antagonist, butoxamine, on the skeletal muscle fibers of rats were investigated. It was found that chronic treatment of rats with clenbuterol caused hypertrophy of histochemically identified fast-twitch, but not slow-twitch, fibers within the soleus, while in the extensor digitorum longus the mean areas of both fiber types were increased; in both muscles, the ratio of the number of fast-twitch to slow-twitch fibers was increased. In contrast, a treatment with butoxamine caused a reduction of the fast-twitch fiber size in both muscles, and the ratio of the fast-twitch to slow-twitch fibers was decreased.

Zeman, Richard J.↗

The pituitary growth hormone cell in space

Growth hormone (GH), produced and secreted from specialized cells in the pituitary gland, controls the metabolism of protein, fat, and carbohydrate. It is also probably involved in the regulation of proper function of bone, muscle and immune systems. The behavior of the GH cell system was studied by flying either isolated pituitary cells or live rats. In the latter case, pituitary GH cells are prepared on return to earth and then either transplanted into hypophysectomized rats or placed into cell culture so that function of GH cells in-vivo vs. in-vitro can be compared. The results from three flights to date (STS-8, 1983; SL-3, 1985; Cosmos 1887, 1987) established that the ability of GH cells to release hormone, on return to earth, is compromised. The mechanism(s) responsible for this attenuation response is unknown. However, the data are sufficiently positive to indicate that the nature of the secretory defect resides directly within the GH cells.

Hymer, Wesley C.↗

Experiment K-6-09. Morphological and biochemical investigation of microgravity-induced nerve and muscle breakdown. Part 1: Investigation of nerve and muscle breakdown during spaceflight; Part 2: Biochemical analysis of EDL and PLT muscles

The present findings on rat hindlimb muscles suggest that skeletal muscle weakness induced by prolonged spaceflight can result from a combination of muscle fiber atrophy, muscle fiber segmental necrosis, degeneration of motor nerve terminals and destruction of microcirculatory vessels. Damage was confined to the red adductor longus (AL) and soleus muscles. The midbelly region of the AL muscle had more segmental necrosis and edema than the ends. Macrophages and neutrophils were the major mononucleated cells infiltrating and phagocytosing the cellular debris. Toluidine blue-positive mast cells were significantly decreased in Flight AL muscles compared to controls; this indicated that degranulation of mast cells contributed to tissue edema. Increased ubiquitination of disrupted myofibrils may have promoted myofilament degradation. Overall, mitochondria content and SDH activity were normal, except for a decrease in the subsarcolemmal region. The myofibrillar ATPase activity shifted toward the fast type in the Flight AL muscles. Some of the pathological changes may have occurred or been exacerbated during the 2 day postflight period of readaptation to terrestrial gravity. While simple atrophy should be reversible by exercise, restoration of pathological changes depends upon complex processes of regeneration by stem cells. Initial signs of muscle and nerve fiber regeneration were detected. Even though regeneration proceeds on Earth, the space environment may inhibit repair and cause progressive irreversible deterioration during long term missions. Muscles obtained from Flight rats sacrificed immediately (within a few hours) after landing are needed to distinguish inflight changes from postflight readaptation.

Riley, D. A.↗

Effect of hindlimb suspension on cardiovascular responses to sympathomimetics and lower body negative pressure

To determine whether hindlimb suspension is associated with the development of cardiovascular deconditioning, male rats were studied before and after undergoing one of three treatment conditions for 9 days: (1) cage control (n = 15, CON), (2) horizontal suspension (n = 15, HOZ), and (3) head-down suspension (n = 18, HDS). Testing included lower body negative pressure administered during chloralose-urethan anesthesia and graded doses of sympathomimetic agents (norepinephrine, phenylephrine, and tyramine) administered to conscious unrestrained animals. Both HDS and HOZ were associated with a small decrease in the hypotensive response to lower body negative pressure. The HOZ group, but not the HDS group, exhibited augmented reflex tachycardia. Furthermore, both HDS and HOZ groups manifested reduced pressor responses to phenylephrine after treatment. These reductions were associated with significantly attenuated increases in mesenteric vascular resistance. However, baroreflex control of heart rate was not altered by the treatment conditions. Collectively, these results indicate that 9 days of HDS in rats does not elicit hemodynamic response patterns generally associated with cardiovascular deconditioning induced by hypogravic conditions.

Overton, J. Michael↗

Effect of body weight gain on insulin sensitivity after retirement from exercise training

The effect of the body-weight gain after retirement from an exercise-training program on the retained increase in insulin sensitivity elicited by the training was investigated in exercise-trained (ET) rats. Insulin sensitivity was assessed by oral glucose tolerance and insulin suppression tests immediately after training and during retirement. Results show that, compared with sedentary controls, exercise training enhanced insulin-induced glucose uptake, but the enhanced sensitivity was gradually lost with the end of running activity until after seven days of retirement, when it became equal to that of controls. This loss of enhanced sensitivity to insulin was associated with an accelerated gain in body weight beginning one day after the start of retirement. However, those animals that gained weight only at rates similar to those of control rats, retained their enhanced sensitivity to insulin.

Dolkas, Constantine B.↗

Cosmos 1887 - Science overview

Twenty two groups of U.S. investigators participated in joint studies of ten male rats flown on the Cosmos 1887 biosatellite. A summary of these studies embracing skeletal muscle, bone, endocrine, neural, intestinal, metabolic, immunology, cardiac, and gonadal investigations is presented. Three general objectives of the rat experiments are outlined - verification of previous observations of the biological responses to microgravity; clarification of the effects of microgravity on both the tissues investigated and the measurements performed; and relation of biological responses to flight duration. It is concluded that the first objective is met fully and the second with a varying degree of success. The confounding effects of overshooting the designated landing site and delayed recovery of the animals largely precluded meeting the last objective. It is also noted that investigations were performed for the first time on brain and spinal cord enzymes, a neurotransmitter, transmitter receptors, hypothalamic regulatory factors, pineal metabolites, atrial granules, liver histology, and jejunal mitotic rate in spaceflight animals.

Grindeland, R. E.↗

Cosmos: 1989 immunology studies

The effects of flight on Cosmos mission 2044 on leukocyte subset distribution and the sensitivity of bone marrow cells to colony stimulating factor-GM were determined. A parallel study with antiorthostatic suspension was also carried out. The study involved repetition and expansion of studies performed on Cosmos 1887. Spleen and bone marrow cells were obtained from flown, vivarium control, synchronous control, and suspended rats. The cells were stained with a series of monoclonal antibodies directed against rat leukocyte cell surface antigens. Control cells were stained with a monoclonal antibody directed against an irrelevant species or were unstained. Cells were then analyzed for fluorescence using a FACSCAN flow cytometer. Bone marrow cells were placed in culture with GM-CSF in McCoy's 5a medium and incubated for 5 days. Cultures were then evaluated for the number of colonies of 50 cells or greater.

Sonnenfeld, Gerald↗

Three Hierarchies in Skeletal Muscle Fibre Classification Allotype, Isotype and Phenotype

Immunocytochemical analyses using specific anti-myosin antibodies of mammalian muscle fibers during regeneration, development, and after denervation have revealed two distinct myogenic components determining fiber phenotype. The jaw-closing muscles of the cat contain superfast fibers which express a unique myosin not found in limb muscles. When superfast muscle is transplanted into a limb muscle bed, regenerating myotubes synthesize superfast myosin independent of innervation. Reinnervation by the nerve to a fast muscle leads to the expression of superfast and not fast myosin, while reinnervation by the nerve to a slow muscle leads to the expression of a slow myosin. When limb muscle is transplanted into the jaw muscle bed, only limb myosins are synthesized. Thus jaw and limb muscles belong to distinct allotypes, each with a unique range of phenotype options, the expressions of which may be modulated by the nerve. Primary and secondary myotubes in developing jaw and limb muscles are observed to belong to different categories characterized by different patterns of myosin gene expression. By taking into consideration the pattern of myosins synthesized and the changes in fiber size after denervation, 3 types of primary (fast, slow, and intermediate) fibers can be distinguished in rat fast limb muscles. All primaries synthesize slow myosin soon after their formation, but this is withdrawn in fast and intermediate primaries at different times. After neonatal denervation, slow and intermediate primaries express slow primaries hypertrophy with other fibers atrophy. In the mature rat, the number of slow fibers in the EDL is less than the number of slow primaries. Upon denervation, hypertrophic slow fibers matching the number and topographic distribution of slow primaries appear, suggesting that a subpopulation of the slow primaries acquire the fast phenotype during adult life, but reveal their original identity as slow primaries in response to denervation by hypertrophying and synthesizing slow myosin. It is proposed that within each muscle allotype, the various isotypes of primary and secondary fibers are myogenically determined, and are derived from different lineage of myoblasts.

Hoh, Joseph F. Y.↗

COSMOS 2044: Lung morphology study, experiment K-7-28

Researchers examined the effect of microgravity during spaceflight on lung tissue. The ultrastructure of the left lungs of 5 Czechoslovakian Wister rats flown on the 13 day, 19+ hour Cosmos 2044 mission was examined and compared to 5 vivarium and 5 synchronous controls at 1-g conditions, and 5 rats exposed to 14 days of tail suspension. Pulmonary hemorrage and alveolar adema of unknown origin occurred to a greater extent in the flight, tail-suspended, and synchronous control animals, and in the dorsal regions of the lung when compared with the vivarium controls. The cause of these changes, which are possibly due to an increase in pulmonary vascular pressure, requires further investigation.

Elliott, Ann R.↗

Atrial natriuretic factor increases vascular permeability

An increase in central blood volume in microgravity may result in increased plasma levels of atrial natriuretic factor (ANF). In this study, it was determined whether ANF increases capillary permeability to plasma protein. Conscious, bilaterally nephrectomized male rats were infused with either saline, ANF + saline, or hexamethonium + saline over 2 h following bolus injections of (I-125)-albumin and (C-14)-dextran of similar molecular size. Blood pressure was monitored, and serial determinations of hematocrits were made. Animals infused with 1.0 microg/kg per min ANF had significantly higher hematocrits than animals infused with saline vehicle. Infusion of ANF increased the extravasation of (I-125)-albumin, but not (C-14)-dextran from the intravascular compartment. ANF also induced a depressor response in rats, but the change in blood pressure did not account for changes in capillary permeability to albumin; similar depressor responses induced by hexamethonium were not accompanied by increased extravasation of albumin from the intravascular compartment. ANF may decrease plasma volume by increasing permeability to albumin, and this effect of ANF may account for some of the signs and symptoms of space motion sickness.

Lockette, Warren↗

International Union of Physiological Sciences Commission on Gravitational Physiology, Annual Meeting, 11th, Lyons, France, Sept. 25-27, 1989, Proceedings

Topics discussed include recent space flight results in gravitational physiology, cardiovascular changes, current concepts in gravitational physiology, musculoskeletal changes, gravity and the cardiovascular system, hypergravic conditions, and head-down tilt. Papers are presented on the effect of space flight on the ultrastructure of the rat cerebellar and hemisphere cortex, a comparative study of cardiovascular responses in primates exposed to tilt test and lower body positive pressure, catecholamines during short- and long-term head-down bedrest, and effects of a 40-day tail-suspension on rat weight-bearing bones. Attention is also given to otolith versus vertical semicircular canal input in the inhibition of horizontal postrotatory nystagmus, cardiovascular responses to sustained acceleration, effects of high sustained hypergravity on plasma catecholamines, and the carotid baroreceptor cardiac-vagal reflex responses during 10 days of head-down tilt.

Reynolds, Orr E.↗