[Dynamics of rat's soleus muscle recovery from the suspension-induced atrophy].

Dynamics of the 60-d soleus recovery was studied morphologically and histomorphometrically in female rats exposed to 30-d tail-suspension. Suspension led to soleus atrophy manifested by substantial losses in mass (56% vs. the control) and cross-sectional area of myofibers, and partial transformation of slow fibers into fast. The most intensive recovery processes in the soleus, reverse to the atrophic ones, were observed in the period between days 2 and 8 of readaptation, but then they subsided. Full recovery of the soleus mass and CSA took approximately 60 days of readaptation. Fast myofibers are less susceptible to atrophy and, therefore, recovered sooner than the slow ones. Percentage of slow-to-fast fibers returned to the norm between days 14 and 30. In addition to the persisting atrophy on readaptation day 2, there were some hemodynamic disorders in the soleus fraught with interstitial edema, distortion of muscle trophism, dystrophic developments in muscle fibers, and death of a number of fibers. Edema faded away between days 8 and 14 of readaptation. Recovery of the soleus muscle was considerably compromised by hemodynamic disorders at the beginning of readaptation.

[Muscle atrophy in microgravity and during its simulation].

Summarized are the results of comparative analysis of morphological changes in rat's skeletal muscles after microgravity and its simulation. On completion of space flight, hindlimb muscles of rats exhibited atrophy developed in space microgravity in consequence of the lack of weight-bearing loads and changes solely in the slow anti-g muscles due to the hemodynamic disorders appearing after space flight. Immobilization combined with clinostatting cannot be a veridical laboratory model of microgravity, as horizontally positioned animals still possess weight and, besides, experience severe chronic stress of immobilization. Tail suspension with the head-end permanently down and the hind limbs out of use appeared the most demonstrative model of the space microgravity effects. With this model, the hindlimb muscles underwent changes identical to what had been observed in space flown animals. Data of the simulation studies suggest stabilization of muscle atrophy at a certain level and an earlier and stronger reaction to the hindlimb unloading in young rats as compared to old animals. Skeletal muscles in females and males responded to suspension similarly in spite of difference in the hormonal status.

[The combined effect of retabolile and support loads on the post-traumatic reparation process in suspended rat muscles]. / Sochetannoe deistvie retabolila i opornykh nagruzok na posttravmaticheskii reparativnyi protsess v myshtsakh krys pri vyveshivanii.

Histological and histomorphometric technical were used to determine effects of limited support loads and anabolic steroid retabolite on the time course of the post-traumatic reparation of m. soleus and m. gastrocnemius in tail-suspended rats in the 14-d experiment. One day prior to suspension, the muscles were partly crushed after the rats had been anesthetized with the help of artery clamp. Deprivation of the support loading was shown to cause atrophy of m. soleus and, to a less degree, m. gastrocnemius and inhibit the post-traumatic reparation of m. soleus. Neither retabolite injection (at the total dose of 5 mg per 100 g of the body mass) nor daily limited support loading (the rats were free from suspension and could stand on all four limbs 2 hrs a day) could essentially prevent muscle atrophy and enhance reparation. Nonetheless, combination of the support loads with retabolite injection implicitly slowed atrophy and stimulated healing of m. soleus trauma.

[Hindlimb antigravity muscles' reaction in male and female rats to the deficit of functional loading]. / Reaktsiia antigravitatsionnykh myshts zadnikh konechnostei samtsov i samok krys na defitsit funktsional'nykh nagruzok.

Histological and histomorphometric comparison of the antigravity muscles of rats of both sexes was performed following 30-d unloading of their hind limbs by head-down suspension. It was shown that growth rate of control males was higher as compared to control females. This is attributed to the synergic effects of somatotropin and testosterone on metabolism and growth of males and only somatotropin in females. Load deprivation of the hind limbs inhibited body mass gain in all animals; however, this inhibition was twice as great in males. Increase of the soleus and gastrocnemius in the control males in this experiment was slightly ahead of the muscle mass gain in the females. The histomorphometric investigation of the cross-section area of myofibers did not reveal differences between males and females either in the control or suspension. No difference was found in percent of various types of fibers in the control males and females. In the soleus of the suspended rats, a part of slow fibers had transformed into fast ones without any sex-related particularities. The conclusion was made that despite the significant difference in the hormonal profile, the reaction of males and females to insufficient weight loading of the antigravity muscles was alike.

[The effect of retabolil and support loads on atrophied muscles in suspended rats]. / Vliianie retabolila i opornykh nagruzok na podvergavshiesia atrofii myshtsy u vyveshannykh krys.

In experiments with rats histological and morphometric methods were employed to study effects of anabolic steroid rhetabolil and a combination of rhetabolil with predetermined support loads on development of atrophy in m. soleus and m. gastrocnemius. Muscular atrophy was provoked by tail suspension of rats for a period of 30 days. Rhetabolil was injected once a week I/M at a total dose of 10 mg per 100 g of the body mass. The experiment showed that this dose of rhetabolil had no effect on atrophy development; neither it amplified the favorable effect of support loads observed in earlier experiments with injection of small doses of rhetabolil. A supposition was made that the anti-atrophy effects of rhetabolil combined with the support loads are dose dependent. It was concluded that large doses of rhetabolil do not activate anabolic processes in the load-deprived muscles.

[Peculiarities of development of muscular atrophy in rats of varying age due to suspension]. / Osobennosti razvitiia myshechnykh atrofii u krys razlichnogo vozrasta pri vyveshivanii.

Compared were changes in m. soleus and m. gastrocnemius in rats at the age of 40, 100 and 220 days in a 30-d experiment with tail suspendion. As it was stated, deficient support loading of the hind limbs had a negative effect on the gain in m. soleus mass and, to a less degree, in m. gastrocnemius mass, particularly in younger rats. In tail-suspended young rats m. soleus mass was by 60% and in elder rats by 48% less as compared to their controls. No matter age of the group, type-1 fibers and IIA and IIC in m. soleus were equally affected. In comparison with the controls, cross-section areas of fibers in 40- and 100-d old rats decreased by 62-68% and in 220-d old rats, by 43-50%. Slow type 1 muscular fibers underwent transformation in fast type IIA and IIC fibers in m. soleus. The more aged rats, the less population of slow muscular fibers transformed. The m. gastrocnemius mass in all suspended groups was by 20% lower than in the controls. In 40- and 100-d old rats suspension caused atrophy of each of 5 types of fibers in m. gastrocnemius, whereas in 220-d old rats those were only types IA and IIC of fibers that had been atrophied. There were early signs of transformation of slow type IB fibers in the fast ones. The conclusion was made that muscles of young animals are more sensitive to deficit in functional loading and atrophy more severely that in old rats. Transformation of slow fibers was observed mainly in m. soleus of young animals and was essentially absent in old.

[Characteristics of the post-traumatic reparative process in the M. soleus of rats subjected to extended suspension]. / Osobennosti posttravmaticheskogo reparativnogo protsessa v kambalovidnoi myshtse krys pri dlitel'nom vyveshivanii.

Histological methods were applied to study the course of post-traumatic reparation of m. soleus in rats subjected to a 30-d head-down suspension. Muscles in unconscious animals were traumatized on day 15 of suspension by crushing a small part with the artery clamp. Deprivation of the support loading led to development of muscle atrophy so that mass of the muscle in sacrificed animals was by 53.7% less as compared to the controls. It was shown that reparation phases in the atrophied muscles were not upset; however, the absolute size of the reparation field was significantly less when compared with the control animals. whereas its relative size was similar to the control. This kind of phenomenon is ascribed to the prevalence of catabolic processes in compromised muscles and consequent decline in production of myoblasts and the connective tissue which forms the frame of the reparative field.

[The characteristics of the reparative process in the muscles when deprived of their functional loads]. / Osobennosti reparatsionnogo protsessa v myshtsakh pri lishenii ikh funktsional'nykh nagruzok.

The time course of repair process in the tonic soleus and phasic gastrocnemius muscles of the head-down tail-suspended rats being traumatized directly prior to suspension or immediately after it. During first, suspension, the animals have been studied on the 17th suspension day and in the second 14-day suspension they were tested on the 14th and 17th post-traumatic days. It was indicated that the suspension results in muscle atrophy with a severely affected m. gastrocnemius loosing more than 40% of its mass. Under the effect of atrophy-induced factors in both muscles there equally occurred an inhibition of both the formation of connective stroma of repair field and the isolation of myoblasts from dedifferentiated muscular fibers due to which an extremely small-size repair field with the irregularly oriented muscular fibers and myoblasts has been originated.

[The effect of support loads and CNS stimulants on the development of the atrophic process in the muscles of suspended rats]. / Vliianie opornykh nagruzok i stimuliatorov TsNS na razvitie atroficheskogo protsessa v myshtsakh vyveshennykh krys.

The histomorphometric method there was used to study effects of ephedrine, strychnine, and support loads on the atrophy of m. soleus and m. gastrocnemius in rats with load-deprived lower extremities (14-day tail-suspension). Deficiency of support loads on the lower extremities led to atrophy of the muscles, especially the slow m. soleus. Injections of ephedrine (0.06 mg/kg), strychnine (0.015 mg/kg) as well as ephedrine and strychnine at one and the same time did not affect the development of atrophy. On the contrary, daily 2-hr support loading of the rear extremities had a favourable effect on the muscle atrophy as it was slowed down. Particularly effective were injections of ephedrine on the background of support loads following which the mass of m. soleus in the suspended rats was close to vivarium control. It is suggested that the preventive effect of ephedrine is associated with stimulating the CNS controllers of the somatotropic function of the pituitary body and eventual enhancement of the somatotropic hormone production.

[Dynamics of atrophic processes in the rat's muscles under the deficiency of support loads]. / Dinamika atroficheskogo protsessa v myshtsakh krys pri defitsite opornykh nagruzok.

In the 14, 3 and 90 day-experiments with tail-suspended rats, histochemical determination of myosin ATP-ase activity in m. soleus and m. gastrocnemius preincubated in acid and neutral media was followed by measurement of the cross-sectional areas (CSAs) of muscular fibers (MF) and calculation of the percentage of various types of MF. By day 30 of testing atrophy in m. soleus reached maximum and stabilized. By that time, MF CSAs were less than in the control by 69, 62, and 68% in MF-I, -IIA and -IIC, respectively. Slow MF underwent the transformation into fast and intermediate. In slow MF this process peaked by day 3 when the number of these fibers decreased by 28% as compared to the control, and stabilized. The transformation of intermediate fibers into the fast ones was progressing simultaneously. This process was not finished by day 90. Atrophy of m. gastrocnemius was less pronounced than in m. soleus. On day 14 of experiment, MF CSAs, except for IIB, were by 30% smaller than in the control. Type IIB MF were less affected as their CSAs decreased by only 17% as compared with the control. On day 90, CSAs in both slow and IIC-type fast MFs remained approximately same as in the rats investigated on day 14. Fast MF CSAs either tended to (IIA) or regained (IIB) the norm. Hence, atrophy in m. gastrocnemius stabilized earlier than in m. soleus. Besides, longer suspension led to a partial or complete reconstruction of two out of three types of fast fibers. The percent ratio of MFs was unchanged; however, during the ATP-ase determination slow IB-type MFs assumed th color typical of fast MFs.

[A morphological study of skeletal muscles of rats flown aboard the space laboratory SLS-2]. / Morfologicheskoe issledovanie skeletnykh myshts krys, éksponirovannykh na bortu amerikanskoi kosmicheskoi laboratorii SLS-2.

M. soleus and m. gastrocnemius in rats flown aboard SLS-2 during 14 days have been studied histologically and electron-microscopically. It is found that the stay in a weightless environment causes muscular atrophy which is more pronounced in m. soleus. In rats killed on Day 13 of the flight and in five hours post-flight the morphological picture of the muscles was similar although in rats killed postflight the number of dystrophic changed fibers was greater. The availability of the active satellite cells, myoblasts and muscular tubes was indicative of a preserved regenerative capacity of the muscles. After a lapse of 14 days of readaptation to terrestrial gravity the size of muscular fibers in the rats of flight group has reached the level of control animals although the contractile apparatus of m. soleus did not restore completely. In the rats of this group m. soleus had the foci of small newly forming muscular fibers evidently appeared at the sites of fiber destruction as a result of hemodynamic disorders accompanying the transition from microgravity to terrestrial gravitation. Total number and number of functioning capillaries in the rats of flight groups did not change.

[Effects of ibandronate on the osteopenia process in tail-suspended rats]. / Vliianie ibandronata na razvitie osteopenii u vyveshennykh krys.

Histological and histomorphometric effects of ibandronate on the metaphyseal spongiosis in tibia were studied in tail-suspended rats and their controls in a 30-d experiment. Ten- to twenty-day course of ibandronate at a dose of 6 micrograms/kg of the body mass per diem altered the architectonics of metaphyseal spongiosis and increased materially the total spongiosis volume no matter whether those were suspended rats or controls. Spongiosis growth was a result of a sharp deterioration of resorption and spongy bone remodelling due to ibandronate. The substance also exhibited a strong durable action inferring that it might be used for prevention of osteopenia for lack of loading on the musculoskeletal system.

[Effect of gravitation loading and retabolil on development of atrophy in muscles and bones of rats due to suspension]. / Vliianie opornykh nagruzok i retabolila na razvitie atroficheskikh protsessov v myshtsakh i kostiakh krys pri vyveshivanii.

In a 3-wk experiment with tail-suspended rats histological and histomorphometric methods were used to determine the effects of graded gravitational loading (GGL) and anabolic steroid retabolil (nortestosterone decanoate) on the course of atrophy in soleus m. (SM), gastrocnemius m. (GM), tibia and humerus, and functioning of somatotrophic hormones (STH) of the pituitary and thyrocytes of the thyroid. Suspension was found to produce atrophy in SM and, to a less degree, in GM, partial transformation of SM slow fibers into the fast ones, suppression of the tibial longitudinal growth, demineralization of the tibial and humeral spongious metaphyses; besides, functional activities of STH-cells and thyrocytes were inhibited. Graded gravitational loading of rats by intermittence of suspension for 2 hrs slowed down atrophy in both muscles and osteopenia in tibia, stimulated the synthetic and secretory functions of STH-cells without any marked effect on thyrocytes or humeral osteopenia. GGL failed to influence the slow-to-fast transformation of SM fibers. Two injections of retabolil at the total dose of 3 mg/kg of the body mass somewhat interfered with the SM atrophy and humoral osteopenia, and were favorable to the synthetic but not secretory activity of STH-cells. Neither SM and tibial atrophies nor thyroid activity of the gland were improved. The prophylactic action of GGL upon the SM and humeral atrophies was significantly higher when combined with retabolil, whereas GM and tibia were not noticeably cured by retabolil. Inhibition of the SM atrophy and humeral osteopenia in rats treated with GGL and retabolil concurred with elevated activities of STH-cells and thyrocytes indirectly suggesting their more intensive production of the growth hormone and thyroid hormones, respectively.

[Role of the hypophysis, hormonal growth inducers and physical exercises in the regulation of function of thyrocytes, C-cells and parathyrocytes in rats during simulated weightlessness]. / Rol' gipofiza, gormonal'nykh induktorov rosta i fizicheskikh uprazhnenii v reguliatsii funktsii tirotsitov, C-kletok i paratirotsitov u krys pri modelirovanii nevesomosti.

Immunohistochemistry and histomorphometry were employed to assay thyroid and parathyroid glands in hypophysectomized rats following a10-day tail suspension in head-down position and daily injection of either physiological solution or growth hormone or insulin-like growth factor 1 on the background of physical exercise, i.e. ascent up a 1 m high staircase with a load fastened to the tail. Hypophysectomy was found to cause atrophic/sclerotic changes in the thyroid and parathyroid glands, and dramatically suppress the functional activity of thyrocytes, C-cells (calcitonin producers) and parathyrocytes (parathormone producers). Assumingly, the impairing effect of hypophysectomy on C-cells and parathyrocytes is consequent to the reduced production of thyroid hormones and concomitant moderation of metabolism. The suspension by tail added somewhat to the severity of changes in thyroid and parathyroid glands under the effect of hypophysectomy, whereas the injection of growth hormone or insulin-like growth factor 1 slightly stimulated thyrocytes, C-cells, and parathyrocytes activities; however, it failed to offset the hypophysectomy-provoked developments. Although the activities of thyrocytes, C-cells or parathyrocytes were not affected by physical exercise, there was a mild C-cell proliferation.

[Examination of skeletal muscles of rats after a short-term flight on Cosmos-1667]. / Issledovanie skeletnykh myshts krys posle kratkovremennogo kosmicheskogo poleta na biosputnike "Kosmos-1667".

Using morphological and histochemical methods, skeletal muscles (soleus, gastrocnemius), quadriceps and biceps muscles) of Wistar-SPF rats flown for 7 days on Cosmos-1667 were investigated. The short-term exposure to microgravity led to muscle atrophy which primarily involved myofibers with a high level of oxidative metabolism and a low level of ATPase activity. The percentage composition of myofibers of different types remained unchanged. The soleus muscle showed the greatest changes which included both atrophic and dystrophic shifts. Muscle atrophy developed together with metabolic changes that resulted in glycogen accumulation and decreased SDH activity. After return to Earth's gravity microcirculation disorders were seen only in the soleus muscle.

[Morphological study of the muscle fibers and the microcirculatory bed of the muscles in monkeys during head-down tilt hypokinesia]. / Morfologicheskoe issledovanie myshechnykh volokon i mikrotsirkuliatornogo rusla myshts obez'ian pri antiortostaticheskoi gipokinezii.

Primates were exposed to head-down tilt for 7 and 12 days. As the study continued, the body mass and muscle mass decreased, muscles became atrophic, and the number of functioning capillaries lessened. Out of the three muscles examined (gastrocnemius, soleus, and biceps brachii), the soleus muscle showed the greatest changes. It can be concluded that, in spite of blood redistribution and blood pooling in the upper body (seen during autopsy), no blood displacement occurs in the microcirculatory bed. The decrease in the number of functioning capillaries is normally regarded as a change that is concomitant with muscle atrophy.

[Morphohistochemical study of skeletal muscles in rats after experimental flight on "Kosmos-1887"]. / Morfogistokhimicheskoe issledovanie skeletnykh myshts krys v éksperimente na biosputnike "Kosmos-1887".

Morphometric and histochemical methods were used to examine the soleus, gastrocnemius (medial portion), quadriceps femoris (central portion) and biceps brachii muscles of Wistar SPF rats two days after the 13-day flight on Cosmos-1887. It was found that significant atrophy developed only in the soleus muscle. The space flight did not change the percentage content of slow (type I) and fast (type II) fibers in fast twitch muscles. During two days at 1 g the slow soleus muscle developed substantial circulation disorders, which led to interstitial edema and necrotic changes. The gastrocnemius muscle showed small foci containing necrotic myofibers. Two days after recovery no glycogen aggregates were seen in myofibers, which were previously observed in other rats examined 4--8 hours after flight. An initial stage of muscle readaptation to 1 g occurred, when NAD.H2-dehydrogenase activity was decreased.