Intermittent acceleration as a countermeasure to soleus muscle atrophy DOMINICK DONALD Department

S. D’AUNNO, B. THOMASON,

RONALD R. ROBINSON, GREGORY AND FRANK W. BOOTH

S. SMITH,

of Physiology and Cell Biology, University of Texas Medical School, Houston, Texas 77225

D'AUNNO,DOMINICKS.,RONALDR. ROBINSON,GREGORYS. ments be conducted so that a sufficient level of data and SMITH, DONALDB. THOMASON,ANDFRANKW. BOOTH.Interexpertise can be obtained in preparation for the expenmittent

acceleration

as a countermeasure

to soleus muscle atro-

phy. J. Appl. Bhysiol. 72(2): 428-433, 1992.-The centrifuge proposedfor the SpaceStation will most likely be used,in part, for countermeasurestudies. At present, there is a paucity of information concerningthe duration and frequency of acceleration necessaryto counteract the atrophy process associated with microgravity. The present study was designedto investigateintermittent acceleration during non-weight bearing of the soleusmuscle and its resultant effects on muscular atrophy. Each day rats were removed from hindlimbs suspensionand acceleratedto 1.2g for four 15-min periodsevenly spacedover a 12-h interval. The soleusmuscleexperienced non-weight bearing the remaining 23 h each day. This paradigm, when repeated for 7 days, did not completely maintain the massof soleusmuscle, which was 84% of control. Interestingly, the identical protocol utilizing ground support in lieu of acceleration successfully maintained the soleusmuscle mass. The failure of the centrifugation protocol to adequately maintain soleusmuscle massmight be dueto an undefined stressplaced on the animals inherent in centrifugation itself. This stress may also explain the transient declinein food intake of the intermittent acceleration group on the 2nd and 3rd days of treatment. Also, these data support the concept that the frequency of exposure, as opposedto the duration of exposure, to weight bearing during hindlimb unweighting seemsto be the more important determinant of maintaining postural musclemass. skeletal muscle;prevention of muscle atrophy; hindlimb nonweight bearing; centrifugation THE RAT SOLEUSMUSCLE has been extensively

used as a model of postural or antigravity (type I) muscle (20). Ninety-six percent of its myosin heavy-chain protein is of the slow isoform type (22). It is well known that on exposure to either weightlessness or Earth-based nonweight bearing there is a preferential atrophy of type I muscle (17, 18, 20). This atrophy represents a serious health risk for long-duration space missions. Consequent to the muscle-type loss, there is a decrease in the amount of endurance capability (11,12). It is feared that the effectiveness and safety of extravehicular activities may be compromised as well as the strength and ability to maintain and operate spacecraft. The concern generated from these data, in part, have lead to the addition of a smallanimal centrifuge to the Space Station so that the effectiveness of countermeasure studies and other gravity related experiments can be determined (3). Therefore, it is imperative that ground-based centrifugation experi428

0161-7567192

$2.00 Copyright

0

sive and realistically infrequent space-based animal-centrifugation experiments. Recently, it has been shown that the mass of non-weight-bearing soleus muscle can be maintained if the rats are removed from non-weight bearing and subjected to ground support (4 times a day, lasting 10 min each, over a 7-day period) (4,810). It is unknown whether intermittent acceleration would substitute for ground support in this paradigm. Our goal was to ascertain the effectiveness of intermittent acceleration at 1.2 g in maintaining the mass of the non-weightbearing soleus muscle. We hypothesized that centrifugation would serve as an effective countermeasure and successfully maintain the soleus muscle mass at pretreatment values. MATERIALS AND METHODS Animals. Pathogen-free Sprague-Dawley female rats were obtained from Sasco (Houston, TX). They were acclimatized to the animal quarters for 3 wk and then randomly assigned to one of the following five groups at 8 wk of age. 1) Day 0 or precontrol rats (n = 8) received no treatments and were killed at the start of the experiment. 2) The postcontrol group (n = 7) was placed into individual cages during the treatment period but otherwise received no additional treatment and was killed with the treatment groups. 3) The non-weight-bearing group (n = 6) was exposed to continuous hindlimb unweighting for 24 h each day for 1 wk. 4) The non-weight-bearing with intermittent acceleration group (n = 9) underwent centrifugation to produce 1.2 g during four 15-min bouts at the starting times of 0700,1100,1500, and 1830 each day for the period of 1 wk. Before acceleration, rats were removed from hindlimb non-weight bearing and placed into centrifuge cages. The remaining 23 h of the day were spent in hindlimb non-weight bearing. 5) The nonweight-bearing with intermittent ground support group (n = 5) received four 15min bouts of ground support at the starting times of 0715, l115i 1515, and 1845 each day for 1 wk. Each 15-min period, these rats were removed from hindlimb non-weight bearing and placed into the centrifuge cages on the centrifuge but were not accelerated. The small-animal centrifuge was in a separate lighted room maintained at 20-22OC. The remaining 23 h of the day were spent in hindlimb non-weight bearing in a room shared with the other rats in the experiment. This room was kept at 20-22OC with light cycle from 0700-

1992 the

AmericanPhysiologicalSociety

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. 4

A net

B------RR A: acceleration vectors. g, acceleration due to gravity (9.81 m/s2); Anet, net acceleration; W,angular velocity of centrifuge (in rad/s). B: centrifuge. r,,, radius of centrifuge at rest; r, length of dependent arm of centrifuge; 8, angle between r, and r; R, derived length that represents radius of centrifuge in any state. See APPENDIX for derivation. FIG.

1.

1900 followed by a 12-h dark cycle. Food and water were provided ad libitum while the rats were in this room. Food intake was recorded. Treatments. The rats underwent non-weight bearing using the model described earlier (22). In brief, the tail of the rat was cleaned with 70% isopropyl alcohol and was air dried . A thin coating of 25% benzoin-75% isopropyl alcohol was applied to the tail and dried with warm air. This gave a tacky surface to the tail. Two strips of adhesive firm X foam (Protek-Toe Products, Hackensack, NJ) were applied to the cephalic half of the tail and secured with elastic adhesive bandage (Elastoplast). The tail cast, now in place, was attached via a snap to a swivel suspended from a clamp placed above the cage. The swivel allowed free 360° rotation by the rat. Clamp height was adjusted so that the rat could support itself on its forelimbs while the hindlimbs were elevated to prevent contact with the cage floor and was adjusted to minimize lordosis. The groups for acceleration and ground support were removed from non-weight bearing by unclasping a snap from the swivel. Rats were placed by sets of four in a 30.7 cm X 32 cm X 17.9 cm (depth X width X height) Plexiglas holding unit with a nontransparent top. Holding units were then placed into an arm of the centrifuge. The ground support group did not receive acceleration. The acceleration group underwent 1.2 g determined as described in the APPENDIX and illustrated in Fig. 1. During acceleration, rats were observed to move about sporadically, but physical activity was not quantified. After the 7 days of treatment, rats were given pento-

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baritol sodium (50 mg/kg body wt ip) immediately after the final bout of centrifugation or ground support. Rats that were non-weight bearing only were anesthesized while non-weight bearing. Soleus muscles and plantaris muscles were excised, frozen in liquid-nitrogen-cooled Wollenberger tongs, and stored at -8OOC until assay for protein by the biuret procedure (7). Adrenal glands were also removed and weighed. The quantity of soleus muscle in the experimental groups is expressed five ways (Table 1). In addition to soleus muscle wet weight, protein content, and wet weight-to-body weight ratio, soleus muscles in the experimental groups are expressed as two percentages: 1) percentage of control = soleus muscle wet weight in a treatment group/soleus muscle wet weight for combined controls; 2) percent less atrophy = (soleus muscle wet weight of experimental group - soleus muscle wet weight of non-weight-bearing with no treatment group)/ (soleus muscle wet weight of combined controls - soleus muscle wet weight of non-weight-bearing with no treatment group). To determine whether experimental procedures produced sufficient stress to cause ulceration of the stomach, each stomach was removed immediately after exsanguination, briefly rinsed in water to remove particulate matter, and then immersed in phosphate-buffered 10% Formalin (Baxter Scientific Products) for a period of at least 24 h. After fixation, the stomach was opened along the lesser curvature and two 2 mm X lo-mm segments of the glandular epithelium were excised from the same positions in each stomach. These tissue blocks were embedded in paraffin, sectioned, stained with eosin and hematoxylin, and processed for routine light microscopy using standard techniques. All slides were coded so that the scorer was unaware of the experimental group. Using a graded micrometer eyepiece on a Zeiss photomicroscope (Carl Zeiss), tissue sections were evaluated histologically as previously described (13-15). The criteria for evaluating damage are given in Fig. 2. Measurements of the length of surface mucosa injured were made in two separate segments of each stomach, and they were averaged to obtain a single score for each stomach. All values are reported as means t SD. Differences between the various groups were evaluated using the Student-Newman-Keul’s test after a one-way analysis of variance (ANOVA). Remaining data were analyzed with ANOVA. If a significant F value was obtained among the groups, a least significant differences test for unequal replications was employed (16). A value of P < 0.05 was designated as significant. RESULTS

The group receiving ground support for 15 min, four times per day, during non-weight bearing maintained the mass of its soleus muscle (Table 1). However, the group that underwent acceleration for 15 min, four times per day, had a significantly (P < 0.05) reduced wet weight of its soleus muscle compared with the control group (Table 1). Thus intermittent acceleration during non-weight bearing did not maintain the mass of the soleus muscle. The non-weight-bearing with no additional treatment

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1. Soleus weights

TABLE

Soleus Muscle (Pair) Wet Weight Groups

mg

Precontrol Postcontrol Non-weight bearing with No treatments Intermittent ground support Intermittent acceleration

293t36 (8) 281t33 (7)

287t34 (15)

Protein concentration, w/g

Protein content, mg/muscle

Ratio of soleus wet weight to body weight,

% of control

% Less atrophy

100

100

175t47 (4)

53t16 (4)

933t94 (15)

0 67 42

190t49 (6) 220t32 (4) 176H9 (8)

41t14 (6) 56t19 (4) 42t4 (8)

824t118* (6) 953+89t (5) 910t77 (9)

212t25* (6) 258+23t (5) 241t19” (9)

74 90 84

x1o-3

Values are means t SD. Nos. in parentheses are no. of animals. * P < 0.05 from combined controls. 7 P < 0.05 from non-weight bearing with no treatment groups. (See METHODS for percentage equations.)

group also had a significantly (P < 0.05) lower wet weight of the soleus muscle than did the control group (Table 1). The protein concentration in soleus muscle did not differ significantly among the four tested groups (control, nonweight bearing with no additional treatment, non-weight bearing with intermittent centrifugation, and nonweight bearing with intermittent ground support) (Table 1). The protein content per whole soleus muscle did not differ significantly among the four groups, likely as a result of its being a calculated product of two other measurements. The ratio of soleus muscle weight to body weight is significantly (P < 0.05) less than the control group for only one group, the non-weight-bearing with no additional treatment group (Table 1). When the wet weight of the soleus muscle is adju&ted for body weight by a ratio, both non-weight-bearing g&ups receiving intermittent ground support or intermittent acceleration were not different form the combined control group. Thus in one comparison (absolute) intermittent acceleration did not maintain the mass of the soleus muscle while intermittent ground support did maintain mass of soleus muscle. In a second comparison (ratio of muscle to body weight), both groups were not different from control. In an additional set of comparisons, the wet weight of the soleus muscle and the ratio of soleus wet weight to body 100

T I,

Non-weightbearing

.

Non-weightbearing with intermittent acceleration

0 : Type 0 Norma!

Luminal Surface Mucus C& e-1.. unly

Type 1 plus upper gastric pit I. .-. .- C~IIS -,I,mucus

Type 2 plus gastric gland ,,I,, CUIS

Type 3 plus most of glandular ,,:rL,I:. .-

Category of Injury FIG. 2. Microscopic analysis of effect of non-weight bearing and centrifugation on mean percent depth of mucosal injury. Values are means t SD for 6 animals/group. Percent of mucosa b-axis) is identified as a certain histological status (x-axis) of normal or with increasing depths of injury. 0, no histologic?al evidence of injury. No statistical differences exist among grouns within histolotical cateEorization.

weight were signifitintly higher in the non-weight-bearing group receiving intermittent ground support than the non-weight-bearing group with no treatments (Table 1). Body weights before the experimental treatment (pretreatment) were not significantly different among the groups (Table 2). However, ANOVA indicated that a significant difference (P < 0.05) existed among the groups at the end of the treatment period (posttreatment body weights; Table 2). All groups receiving the treatment of hindlimb non-weight bearing had significantly lower (P < 0.05) posttreatment body weights than the control group according to analysis with the least-significant differences for unequal replication (16). The fact that both body weights and soleus muscle wet weights of the control group did not significantly change during the ‘7-day treatment indicates that the difference in soleus muscle weight between the control groups and the non-weightbearing groups is not due to growth of the controls during the 7-day treatment. This is relevant because the hypothesis is that the acceleration countermeasure will maintain the mass of the soleus muscle during its nonweight bearing. All groups with the non-weight bearing treatment have 15-23% significantly (P < 0.05) lower wet weights of the plantaris muscle than does the control group, but no significant differences exist among the groups for the ratio of plantaris to body weight (Table 2). The failure of the countermeasures to prevent atrophy of the fast-twitch plantaris muscle may be related to the absence of nearmaximal tetanic contractions in the countermeasure. Absolute adrenal weights do not differ among groups (Table 2). These results indicate that stress was insufficient to enlarge significantly the absolute adrenal mass on the 7th day of non-weight-bearing over control values. Daily food intakes were affected by the treatment periods. The non-weight-bearing with intermittent ground support group ate significantly (P < 0.05) less than the control group only on the 1st day of non-weight bearing (Table 3). On the other hand, the non-weight-bearing with intermittent centrifugation group ate significantly less for the first 3 days of non-weight bearing. This difference in food intake could be a contributory factor in the failure of intermittent centrifugation to maintain mass of the soleus muscle. No evidence of gastrointestinal injury was found after 7 treatment days (Fig. 2). All groups exhibited similar histolorrv of the stomach mucosa. These observations

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TABLE 2. Body, plantaris muscle, and adrenal weights Plantaris Body Weights, Groups

Precontrol Postcontrol Non-weight bearing with No treatments Intermittent ground support Intermittent acceleration

Pretreatment

Posttreatment

304t148 303221

(7)

313t21

302k12 3Oik9 298t21

(6) (5) (9)

259t16* 272t21” 267t15*

Values are means t SD. * P < 0.05 from

Muscle

(Pair)

Adrenal

Weight

(Pair)

g Wet weight, w

(7) (6) (5) (9)

Ratio of wet weight to body weight, X103

Wet weight, w

Ratio of wet weight to body weight, [email protected]

667t74

2.13t0.17

60.6-tlO.5

194t29

513t37* 570t64* 523t51*

1.99tO. 16 2.10t0.13 1.96t0.17

65.9k8.8 75.2t15.6 73.1t10.8

256t45’ 276t51* 275t46*

control.

imply that the amount of stress was insufficient duce lasting damage to the stomach’s mucosa.

to pro-

propriate experimental designs for future costly animal countermeasure investigation on the Space Station and costly human countermeasure studies on Earth. DISCUSSION In an earlier study (4, 21), 2 continuous h of ground support for either 1 or 4 wk did not maintain the mass of The information generated in this study demonstrates the non-weight-bearing soleus muscle. However, in the that intermittent ground support is sufficient in mainpresent study, when 1 h of ground support is divided into taining the non-weight-bearing soleus muscle mass while intermittent acceleration at 1.2 g is judged not equally as four 15-min sequences evenly distributed throughout a 12-h period, the mass of the non-weight-bearing soleus effective by some, but not all, measurements. This findmuscle is maintained after 7 days of non-weight bearing, ing was unexpected. The implication is that some undeconfirming earlier reports on intermittent weight bearfined stress associated with acceleration may be responsiing (8-10). The limitation of these findings is that the ble for the result and may interfere with soleus muscle duration of non-weight bearing was only 7 days and docuprotein metabolism. The stress may reduce the protein mentation of the prophylactic effect of intermittent nonsynthesis rate and/or increase the protein degradation weight bearing for 28 days is unknown. Nevertheless, rate, thereby resulting in an overall decrease in muscle present observations show that with one-half the daily mass compared with pretreatment values. rather than conThe failure to adequately maintain the absolute mass duration of weight bearing, intermittent tinuous weight bearing is the more powerful factor in of soleus muscle in the intermittent acceleration group maintaining mass of postural muscle. These results may also be related to the reduction in food intake comimply that the distribution or frequency of weight bearpared with the intermittent ground support group. Both groups had decreased food intakes on the 1st day of ing during a given time frame is a more important detertreatment while the acceleration group continued to eat minant of postural muscle mass than is the total daily time of weight bearing, as given by Bodenheimer’s timeless on the 2nd and 3rd days of the experiment. When animals are placed into hindlimb suspension, there is a intensity summation principle (see Ref. 3 for references). transient decrease in food consumption on the 1st day of The advantage of this finding is that less time needs to be devoted to daily exercise, allowing more time form misunweighting. Then as the animals get accustomed to the sion-oriented tasks. situation, the food intake reaches proportions consistent with that of the control group. Perhaps the added stress We speculate that the efficacy of intermittent, as opof acceleration delays the acclimatization process and re- posed to continuous, exposuve to gravity in maintaining sults in lower food consumption. This could, in part, ex- mass of the non-weight bearing soleus muscle is related plain the decrease in muscle mass. This information sug- to the intermittent weight bearing lessening the decrease gests that animals that are to be accelerated in the Space in the cumulative protein synthesis rate during a 24-h Station centrifuge need to be preacclimatized to acceleraperiod, lessening the increase in protein degradation, or tion before microgravity. This study also reemphasizes both (19). Concerning the potential lessening of the dethe necessity of relatively inexpensive animal expericrease in protein synthesis, the following is known. Durmentation that will enable prudent development of ap- ing the first 5 h of non-weight bearing by the soleus musTABLE 3. Food intakes Food Eaten, g Groups

n

Day

Control Non-weight bearing with No treatments Intermittent ground support Intermittent acceleration

7

26t5

21t4

21t4

1924

20t2

20t2

6 5

18t5* 17t5” 14t4*

171t6 19,t4 14t4*

17rt5 21t6 15t5*

14zt3” 22t3 1724

13t4” 21+4 18t5

15t4 20t4 17t6

9

Values are means t SD. n, No. of observations/day control group.

1

Day

2

for all days except for intermittent

Day

3

Day

4

Day

5

Day

6

acceleration group on day 1 when n = 5. * P < 0.05 from

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cle, mixed and myofibrillar protein synthesis decrease by 16 and 22%, respectively (19). In a similar manner, rates of mixed protein synthesis decline quickly in muscles fixed at less than their resting lengths in immobilized limbs. After only 6 h of immobilization, a 20% decrease in mixed protein synthesis rate occurs in the soleus muscle (6). Also, a 37% decrease in the rates of mixed protein synthesis transpires in the fast-twitch gastrocnemius muscle during the first 6 h of immobilization (2). From these observations, we speculate that intermittent bouts of ground support repeatedly reverse the rapid decline in protein synthesis rate that occurs immediately on the start of non-weight bearing. However, no data on protein synthesis exist after the return to weight bearing. Previously the increase in protein degradation was calculated to occur after a lag of 3 days of non-weight bearing. Maybe intermittent weight bearing delays the onset of theincrease in protein degradation that occurs in the non-weight-bearing soleus muscle. It is known that intermittent bouts of aerobic exercise during the day, when repeated daily, have the same adaptive effect on maximal oxygen uptake (5) and mitochondria in skeletal muscle (1) that a single daily bout of exercise of equivalent duration to all the intermittent bouts has. Thus the most effective single countermeasure protocol for both the cardiovascular system and postural skeletal muscle in microgravity seems to be intermittent work at one gravity. This information provide a scientific basis for future countermeasure studies. APPENDIX

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tion of 1.20times the acceleration due to earth’s gravity (Anet= 1.20g) as called for in the protocol. From Fig. 1A A2net= (Ru~)~+ g2 A net= v(Ru2j2 + 8

(Al)

From Fig. 1B R = r. + r sin 0

bw

Step 1: find sin $ from Fig. 1 RW2 sin 8 = Anet

(A3) /

Step 2: substitute Eq. A3 into Eq. A2 R=ro+r

rRw2

(A4

net

Step 3: solve Eq. A4 for R

(fm Step 4: substitute Eq. A5 into Eq. Al

(fw

Anet= Step 5: solve Eq. A6 for “=

j//l--J$gi

(fw

net The following is a description of the variables (illustrated in Fig. 1) used in the derivation that follows. R is one-half of the Step 6: substitute the following values into Eq. A7 diameter of the centrifuge. The diameter extends from the Anet= 1.2og g = 9.81 m/s2 center of the cage floor on one sideto the corresponding point on the oppositeside.g is the acceleration due to earth’s gravity r = 0.737 m r. = 0.914 m and w is the angular velocity of the centrifuge in radians per second.A,, is the net acceleration experiencedby the rats dur- The result is o = 2.22 rad/s or 21.20 rpm. ing centrifugation. The angle 8 is the anglebetween the earth’s We thank Drs. Bradford Goodwin and Leslie Yarbrough for suggestgravitational acceleration vector and the net acceleration vector. 0 varies between 0” and 90” depending on the rotational ing that we examine the gastric mucosa, Dr. Yarbrough and Marshall rate of the centrifuge and is equal to the 8 in Fig. 1. In Fig. 1, the Lofton for outstanding support in the animal quarters, Dr. Pauline distance r0 is one-half of the length of the fixed or horizontal Duke for sharing her small-animal centrifuge, andDrs. Frank Sulzman Richard Grindeland for supportive and stimulating conversations. bar of the centrifuge or in other words the length of the fixed andThis research was supported by National Aeronautics and Space portion of one arm of the centrifuge. The distance r is the Administration Grants NAG 2-239 (to F. W. Booth) and NAGW70 (to length of the mobile or dependent portion of one arm of the D. B. Thomason). centrifuge; r extends from the joint between the fixed and moAddress for reprint requests: F. W. Booth, Dept. of Physiology andbile portions of the arm to the center of the cage floor. The Cell Biology, University of Texas Medical School, P.O. Box 20708, vertical arrow designatesthe axis of rotation of the centrifuge. Houston, TX 77225. The following is a list of the numerical valves used in the Received 28 May 1991; accepted in final form 20 August 1991. derivation. g is the acceleration due to earth’s gravity and equals9.81 m/s2,A,, was set by protocol at a value of 1.20 g, r REFERENCES wasmeasuredto be 0.737m, and r. was measuredto be 0.914m. 1. BOOTH, F. W., AND J. 0. HOLLOSZY. Cytochrome c turnover in rat Substituting thesevalues into Eq. 7 from the following derivaskeletal muscles. J. Biol. Chem. 47: 416-419, 1977. tion, one obtains the value of 21.20rpm. While the experiment 2. BOOTH, F. W., AND M. J. SEIDER. Early change in skeletal muscle protein synthesis after limb immobilization of rats. J. Appl. Physwasconducted it was possibleto keep the rotation rate at 21.20 iol. 47: 974-977, 1979. with an error of kO.3 rpm. The accuracy of the centrifuge’s tachometer wascheckedusing a stopwatch at 21.2rpm and was 3. BURTON, R. R. A human-use centrifuge for space stations: proposed ground-based studies. Aviat. Space Environ. Med. 59: 579found to be accurate. 582,1988. The following is a derivation of the subjective acceleration 4. D'AUNNO, D.S.,D.B. THOMASON,AND F.W. BOOTH. Centrifugal experienced by the rats during centrifugation and its expresintensity and duration as countermeasures to soleus muscle atrosion as a function of w. The objective is to determine the rotaphy. J. Appl. Physiol. 69: 1387-1389, 1990. tional rate in revolutions per minute will yield a net accelera- 5. DEBUSK R.F.,U. STENESTRAND, M. SHEEHAN,AND W.L. HAS-

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6. 7. 8. 9. 10.

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KELL. Training effects of long versus short bouts of exercise in healthy subjects. Am. J. Cardiol. 65: 1010-1013, 1990. GOLDSPINK, D. F. The influence of immobilization of stretch on protein turnover of rat skeletal muscle. J. Physiol. Lord. 264: 267282,1977. GORNALL, A. G., C. J. BARDWILL, AND M. M. DAVID. Determination of serum proteins by means of the biuret reagent. J. Biol. Chem. 177: 751-766,1949. HAUSCHKA, E. O., R. R. ROY, AND V. R. EDGERTON. Periodic weight support effects on rat soleus fibers after hindlimb suspension. J. Appl. Physiol. 65: 1231-1237, 1988. HERBERT, M. E., R. R. ROY, AND V. R. EDGERTON. Influence of one-week hindlimb suspension and intermittent high load exercise on rat muscle. Exp. Neural. 102: 190-198, 1988. PIEROTTI, D. J., R. R. ROY, V. FLORES, AND V. R. EDGERTON. Influence of 7 days of hindlimb suspension and intermittent weight support on rat muscle mechanical properties. Aviat. Space Environ. Med. 61: 205-210, 1990. SALTIN, B., G. BLOMQVIST, J. H. MITCHELL, R. L. JOHNSON, K. WILDENTHAL, AND C. B CHAPMAN. Response to submaximal and maximal exercise after bed rest and training. Circulation 38, Suppl. 7: l-78, 1968. SALTIN, B., J. HENRIKSSON, E. NYGAARD, P. ANDERSON, AND E. JANSON. Fiber types and metabolic potentials of skeletal muscles in sedentary man and endurance runners. Ann. NY Acad. Sci. 301: 3-29,1977. SCHMIDT, K. L., R. L. BELLARD, G. S. SMITH, J. M. HENAGAN, AND T. A. MILLER. Influence of prostaglandin on repair of rat stomach damaged by absolute ethanol. J. Surg. Res. 41: 367-377, 1986.

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14. SCHMIDT, K. L., J. M. HENAGAN, G. S. SMITH, P. J. HILBURN, AND T. A. MILLER. Prostaglandin cytoprotection against ethanol-induced gastric injury in the rat. Gastroenterology 88: 649-659,1985. 15. SCHMIDT, K. L., G. S. SMITH, AND T. A. MILLER. Microscopic correlates of adaptive cytoprotection in an ethanol injury model. Histol. Histopathol. 4:105-115,1989. 16. STEEL, R. G. D., AND J. H TORRIE. Principles and Procedures of Statistics. New York: McGraw-Hill, 1960, p. 112-115. 17 STEFFEN, J. M., AND X. J. MUSACCHIA. Effect of hypokinesia and ’ hypodynamia on protein, RNA, and DNA in rat hindlimb muscles. Am. J. Physiol. 247 (Regulatory Integrative Comp. Physiol. 16): R728-R732,1984. 18 . STEFFEN, J. M., AND X. J. MUSCACCHIA. Spaceflight effects on adult rat muscle protein, nucleic acids, and amino acids. Am. J. Physiol. 251 (Regulatory Integrative Comp. Physiol. 20): Rl0591g . Rl063,1986. THOMASON, D. B., R. B. BIGGS, AND F. W. BOOTH. Protein metabolism and P-myosin heavy chain mRNA in unweighted soleus muscle. Am. J. Physiol. 257 (Regulatory Integrative Comp. Physiol. 26): 2. R300-R305,1989. . THOMASON, D. B., AND F. W. BOOTH. Atrophy of the soleus muscle by hindlimb unweighting. J. Appl. Physiol. 68: l-12, 1990. D. B., R. E. HERRICK, AND K. M. BALDWIN. Activity 21. THOMASON, influences on soleus muscle myosin during rodent hindlimb suspension. J. Appl. Physiol. 63: 138-144, 1987. D. B., R. E. HERRICK, D. SURDYKA, AND K. M. BALD22. THOMASON, WIN. Time course of soleus muscle myosin expression during hindlimb suspension and recovery. J. Appl. Physiol. 63: 130-137,1987.

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Intermittent acceleration as a countermeasure to soleus muscle atrophy.

The centrifuge proposed for the Space Station will most likely be used, in part, for countermeasure studies. At present, there is a paucity of informa...
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