Journal of Applied Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Appl Physiol 95: 207-218, 2003; doi:10.1152/japplphysiol.00969.2002
8750-7587/03 $5.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (6)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhang, L.-F.
Right arrow Articles by Wu, X.-Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhang, L.-F.
Right arrow Articles by Wu, X.-Y.

Effectiveness of intermittent -Gx gravitation in preventing deconditioning due to simulated microgravity

Li-Fan Zhang,1 Biao Sun,1 Xin-Sheng Cao,2 Chun Liu,1 Zhi-Bin Yu,1 Le-Ning Zhang,1 Jiu-Hua Cheng,1 Yan-Hong Wu,2 and Xing-Yu Wu2

Departments of 1Aerospace Physiology and 2Aerospace Biodynamics, Fourth Military Medical University, Xi'an 710032, People's Republic of China

Submitted 21 October 2002 ; accepted in final form 26 February 2003


   ABSTRACT
TOP
 ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
This study was designed to compare the effectiveness of daily short-duration -Gx gravity exposure in preventing adverse changes in skeletal and cardiac muscles and bone due to simulated microgravity. Tail suspension for 28 days was used to simulate microgravity-induced deconditioning effects. Daily standing (STD) at 1 G for 1, 2, or 4 h/day or centrifugation (CEN) at 1.5 or 2.6 G for 1 h/day was used to provide -Gx gravitation as a countermeasure. The results indicate that the minimum gravity exposure requirements vary greatly in different systems. Cardiac muscle is most responsive to such treatment: 1 h/day of -Gx gravitation by STD was sufficient to prevent adverse changes in myocardial contractility; bone is most resistant: 4 h/day of -Gx gravitation only partially alleviated the adverse changes in physical and mechanical properties of the femur. The responsiveness of skeletal muscle is moderate: 4 h/day of -Gx gravitation prevented mass reduction and histomorphometric changes in the soleus muscle during a 28-day simulation period. Increasing gravitational intensity to 2.6 G showed less benefit or no additional benefit in preventing adverse changes in muscle and bone. The present work suggests that system specificity in responsiveness to intermittent gravity exposure should be considered one of the prerequisites in proposing intermittent artificial gravity as a potential countermeasure.

rat; hindlimb unweighting; intermittent artificial gravity; countermeasure; myocardial contractility; skeletal muscle; atrophy; bone; osteopenia; centrifugation

ALTHOUGH EXERCISE-BASED COUNTERMEASURES have been practiced with some success for years, these countermeasures are insufficient to prevent postflight cardiovascular dysfunction and to preserve muscle mass and bone density (4, 9, 26, 27, 43, 53, 56). This limitation is due to the fact that exercise and longitudinal loading cannot produce an acceleration field and, hence, cannot restore the stress distribution within the tissues of the body to its normal 1-G level (9, 19, 26, 27, 43, 47, 53, 56). For future long-duration, exploration-class spaceflight, such as travel to Mars, it is likely that gravity-based countermeasures will be required (27, 39, 51, 56). Intermittent artificial gravity (IAG), by incorporation of a short-arm centrifuge into the spacecraft, has been suggested as an alternative (4, 26, 40, 43–46, 56) to continuous artificial gravity (CAG), provided by spinning the entire spacecraft or a tethered rotating spacecraft (27, 39, 45, 51). The major advantage of the IAG protocol would be its potential effectiveness without additional energy systems, control complexity, and high cost. However, little is known about the physiological requirements of intermittent exposure to gravity and the ultimate effectiveness of IAG as a multisystem countermeasure.

In the past two decades, two ground-based human studies have provided promising data demonstrating the effects of daily +Gz gravitation in counteracting the deconditioning due to simulated microgravity. Shulzhenko and Vil-Viliams (40, 46) reported the beneficial effects of daily periodic exposures to +0.8 to +1.6 Gz during 3 or 28 days of dry immersion in alleviating the G tolerance reduction. Vernikos et al. (43, 44) reported that standing or walking for 2 or 4 h/day was effective in most cases to counteract the deconditioning effects of 4 days of -6° head-down bed rest. They concluded that various physiological systems benefit differently from daily short-duration +1 Gz gravitation; i.e., the preventive value appears to be system specific (43, 44).

The tail-suspended, hindlimb-unloaded (HU) rat model has also been used to assess the efficacy of daily gravitation alone or in combination with exercise in alleviating the adverse changes of muscles or bones due to simulated microgravity. Edgerton and colleagues (12, 15, 20, 22, 34, 36), D'Aunno and colleagues (10, 11), and Fitts and colleagues (13, 48, 49) provided convincing evidence that daily standing or exercise for short periods is effective in alleviating the effects of HU on hindlimb muscles of rats. For example, during 7 days of HU, periodic daily standing, very slow walking, or moderate running for a total of 40–60 min, or 3–4% of the total non-weight-bearing time, maintained a near-normal soleus (SOL) mass (12, 20, 22, 34). Centrifugation at 1.2 G (11) or 2.6 G (10) did not show additional benefit. Work on bones has been less relevant. Standing for 2 h/day was ineffective in preventing calcium loss and collagen-matrix reduction in the tibia of 15-day HU rats (23) and bone loss in the humerus of 35-day HU rats (38). It has been suggested that gravitational changes affect tibial growth plates according to Hert's curve; too much or too little loading results in lack of differentiation or closure of the epiphyseal plate (29, 30). However, in each of the aforementioned studies, only the changes in bone or muscle were studied. In addition, no information is available on how daily gravitation may affect changes in cardiac muscle and vessels due to simulated microgravity. Moreover, the experimental design of most of these animal studies did not permit dissociation of the effects of intermittent gravitation from the effects of exercise. Finally, the countermeasure effectiveness should be further evaluated over longer simulation periods, instead of over 7 days of HU (12, 13).

Therefore, we designed the present study to compare the effectiveness of daily gravitations, different in G vector (-Gx or +Gz), intensity, and duration, in preventing the deconditioning in a multitude of organ systems of the same animal during a midterm (4 wk) simulated microgravity. The research goal was to determine whether there are greater differences in physiological requirements of gravity among different organ systems. This study reports the effects of daily short-duration -Gx gravitation by standing (STD) at 1 G or centrifugation (CEN) at 1.5 or 2.6 G in preventing the adverse changes in hindlimb skeletal muscles, bone (femur), and cardiac muscle and discusses the problem of system specificity in G requirements.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Animal Model

Tail-suspended, HU rat model. The technique of tail suspension (31, 50), with modification from our laboratory, has been described in detail previously (8). Briefly, the tail was cleaned, air dried, and sprayed with a generous amount of benzoin and resin. A traction tape was preattached to a plastic bar, attached laterally along the proximal portion of the tail, and then secured by three tape strips. The tail was divided into four quadrants, and only an opposite pair of quadrants (lateral or dorsoventral) was used for application of the traction tape. Tape was replaced weekly using the alternate pair of quadrants. The rats were attached via the plastic bar in the tape to a swivel mounted at the top of the cage, allowing free 360° rotation. The rats were maintained in an about -30° head-down tilt position with their hindlimbs unloaded.

Modes of daily short-duration -Gx gravitation. Two modes of -Gx vector gravitation were used to simulate the counteracting effect of IAG. One mode was stationary ground support, or standing (STD). For STD, the HU rat was removed from suspension and placed in an upright standing position. To restrict ambulatory activity, each rat was placed in a 50-cm-long, tubelike metallic mesh cage, which was maintained in a horizontal position. Food and water were provided ad libitum at the front end of the cage. The other mode of -Gx gravitation was centrifugation (CEN). The animal centrifuge radius is 2 m. The centrifugal acceleration reported is the gravito-inertial resultant. The animals were centrifuged at -Gx vector. For CEN, rats removed from suspension were placed in a 15 x 7 x 10-cm metallic multicompartment cage. During CEN, all animals were placed individually in each compartment, and no food or water was given.

Animals and Experimental Design

Animal care and use. All procedures were reviewed and approved by the Animal Care and Use Committee of the Fourth Military Medical University and conform to the American Physiological Society guidelines on care and use of animals. Male Sprague-Dawley rats were obtained from the Animal Center of the Fourth Military Medical University. The rats were allowed to acclimate to the animal room of our department for 7 days before the onset of each experiment. Rats of each group were housed individually in identical 30 x 26 x 26-cm Plexiglas cages in the same room. Food and water were provided ad libitum throughout the course of the experiment. The animal room was maintained at 23°C on a 12:12-h light-dark cycle (lights on at 0600).

Experimental design. Three separate protocols were carried out in this study.

In protocol 1, the counteracting effectiveness of daily STD of various durations in preventing/alleviating muscle and bone atrophy was evaluated over 28 days of HU. Thirty-five adult male Sprague-Dawley rats (250–260 g body wt) were randomly assigned to five groups (n = 7/group): control (CON), tail suspension (SUS), suspension for 23 h/day and STD for 1 h/day (SUS + STD1), suspension for 22 h/day and STD for 2 h/day (SUS + STD2), and suspension for 20 h/day and STD for 4 h/day (SUS + STD4). During the 28-day period, daily gravitation treatments were conducted between 0800 and 1200.

In protocol 2, the effectiveness of daily treatments at 1 G (STD), 1.5 G, or 2.6 G (CEN) for 1 h/day in preventing/alleviating muscle and bone atrophy was evaluated over 28 days of HU. Thirty male Sprague-Dawley rats (150–160 g body wt) were randomly assigned to five groups (n = 6/group): control (CON), tail suspension (SUS), suspension for 23 h/day and STD for 1 h/day (SUS + STD1), suspension for 23 h/day and centrifugation at 1.5 G for 1 h/day (SUS + CEN1.5G), and suspension for 23 h/day and centrifugation at 2.6 G for 1 h/day (SUS + CEN2.6G). During the 28-day period, treatments were conducted between 1500 and 1700.

In protocol 3, the effectiveness of daily STD for 1, 2, or 4 h/day in preventing contractility depression of cardiac muscle and SOL atrophy was determined over 28 days of HU. Fifty male Sprague-Dawley rats (140–150 g body wt) were randomly assigned to five groups (n = 10/group): control (CON), tail suspension (SUS), suspension for 23 h/day and STD for 1 h/day (SUS + STD1), suspension for 22 h/day and STD for 2 h/day (SUS + STD2), and suspension for 20 h/day and STD for 4 h/day (SUS + STD4). During the 28-day period, treatments were conducted between 0800 and 1200.

Qualitative and Quantitative Alterations in Skeletal Muscles

Tissue preparation and histochemistry. At the end of the 28-day suspension period, the rats from protocols 1 and 2 were anesthetized with pentobarbital sodium (40 mg/kg ip) and killed by exsanguination via the abdominal aorta. The left adrenal and testis were removed and weighed. Four muscles of the left hindlimb, SOL, medial gastrocnemius (MG), lateral gastrocnemius (LG), and extensor digitorum longus (EDL), were removed, trimmed of fat and connective tissue, and weighed. All four muscles were quick-frozen in isopentane, cooled by liquid nitrogen, and stored in a freezer at -70°C. This procedure was completed within 20 min after the muscles were removed from the rats. Within 2 wk of muscle excision, a 5-mm-thick cross section from the mid-belly of each muscle was mounted on a piece of cork with optimum cutting temperature compound. Serial 10-µm-thick cross sections of each muscle were cut in a cryostat at -20°C. The sections were then stained for myosin ATPase at an alkaline pH as described by Nwoye et al. (32).

Image processing. Fibers stained lightly and darkly are referred to as types I and II, respectively. The cross-sectional areas (CSAs) of type I and II fibers and the proportion of type I fibers were determined using an image-processing system (model Q500MC, Leica). For each muscle, five cross sections were taken, and in each section, five microscopic fields were analyzed at x100 magnification. For each muscle, the CSAs of a population of ~500 fibers were determined.

Bone Sampling and Mechanical Testing

The right femurs were immediately removed from each animal and stripped of soft tissues, and their wet weight and middiaphysial diameter (mediolateral aspect) and length were measured using an electronic balance (precision = 1 x 10-4 g; model ACA-100, Denver Instrument) and hand-held precision calipers (±0.02 mm) successively. Their volume was determined by water displacement. Then their dry (118°C for 48 h) and ash (800°C for 24 h) weights were determined. The ratio of wet mass to volume produced an estimate of bone density. The left femurs were removed and kept at -70°C for mechanical testing within 3 days. Frozen specimens were thawed in saline solution at room temperature. Femurs were placed in a material testing machine (model 1195, Instron), supported by two steel rods separated by a distance of 16 mm, and loaded to failure in three-point bending at the middiaphysis with a cross-head speed of 2 mm/min. Data for elastic and maximum loads and coefficients for bending rigidity and bending toughness were obtained and calculated from stress-strain curves.

Contractile Performance of Papillary Muscle

Contractile performance of papillary muscle was determined according to Capasso et al. (6). At the end of the 28-day suspension period, the rats of protocol 3 were anesthetized with ether. The heart was rapidly excised and placed in oxygenated Krebs-Henseleit solution. The left soleus, adrenal, and testis were also removed and weighed. Left ventricular papillary muscle was removed and suspended horizontally in a continuous-perfusion myograph. The solution was maintained at 30°C, bubbled with 95% O2-5% CO2, and perfused at 10 ml/min. The nontendinous end of the papillary muscle was inserted into a spring-loaded clip, which was mounted on a micrometer assembly and used to adjust the muscle length. The tendinous end was tied to the stainless steel hook of a force transducer (model TB-651, Nihon Kohden). Papillary muscle was driven by square-wave impulses (10-ms duration, 130% threshold voltage, 0.2 Hz frequency) from an electronic stimulator (model SEN-3301, Nihon Kohden) through platinum wires placed on both sides of the muscle. The length-tension relation was obtained after an equilibration period of 90 min, during which the length associated with maximum developed force (Lmax) was determined. The length-tension curve was generated by reducing muscle length in 2% Lmax decrements to 88% of Lmax. A reproducible sequence of 10 contractions in each step was selected for analysis. At the end of each experiment, the muscle length at Lmax was measured, the muscle was weighed, and the CSA of the papillary muscle was calculated. The isometric parameters at Lmax, i.e., developed tension (DT), resting tension, peak rate of tension rise, peak rate of tension decline, time to peak rate of tension rise, time to peak tension (TPT), and time to half-relaxation, were measured and calculated.

Statistical Analysis

Values are means ± SE, except body weight data, which are means ± SD. A one-way ANOVA was used to determine the overall differences; then a Student-Newman-Keuls post hoc test was used to determine group differences. The 0.05 level of probability was chosen as significant for all analysis.


   RESULTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Body, Adrenal, and Testis Weight

The results from protocols 1 and 2 are shown in Tables 1 and 2, respectively. Initial body weights were similar among different groups. At the end of 28 days of HU, there were no significant differences in final body weight between CON and SUS rats, but the final body weight was significantly less in various treatment groups than in the respective CON group (P < 0.05 or P < 0.01).


View this table:
[in this window]
[in a new window]
  		Table 1. Body weight and testis and adrenal weights in CON, SUS, and SUS plus daily STD rats of protocol 1

 

View this table:
[in this window]
[in a new window]
  		Table 2. Body weight and testis and adrenal weights in CON, SUS, SUS plus daily STD, and SUS plus daily CEN

 

At the end of the two experiments, the mean wet weights of the left testis of the SUS and the treatment groups were ~44% and ~34% of those of the respective CON group (P < 0.01), and the differences among the SUS and various treatment groups were not significant. There were no significant differences in left adrenal weight among CON, SUS, and treatment groups.

Muscle Weights

The data from protocol 1 are listed in Table 3. After 28 days of HU, the absolute wet weights of SOL, MG, LG, and EDL were 49%, 9%, 20%, and 11% less, respectively, than in CON rats (P < 0.05 or P < 0.01). Daily gravitation significantly attenuated atrophy of SOL: the wet weights of SOL were 38%, 28% (both P < 0.01), and 12% (not significant) less in SUS + STD1, SUS + STD2, and SUS + STD4 rats, respectively. However, for MG, LG, and EDL, the effects on reducing muscle atrophy were significant only when relative wet weights were considered (Table 3).


View this table:
[in this window]
[in a new window]
  		Table 3. Counteracting effects of daily STD in preventing muscle weight reduction during 28 days of simulated microgravity in rats

 

The data from protocol 2 are listed in Table 4. After 28 days of HU, the absolute wet weights of SOL, MG, LG, and EDL were 60%, 22%, 26%, and 10% less, respectively, than in CON rats (P < 0.05 or P < 0.01). Although -Gx gravitation for 1 h/day at 1, 1.5, or 2.6 G attenuated the atrophy of SOL, increasing the G level was associated with a lessened counteracting effect. The wet weights of SOL were 33%, 41%, and 55% less in SUS + STD1, SUS + CEN1.5G, and SUS + CEN2.6G rats, respectively (P < 0.01). The effects in reducing muscle atrophy became more apparent when the changes were considered in terms of relative wet weights of muscles (Table 4).


View this table:
[in this window]
[in a new window]
  		Table 4. Counteracting effects of daily STD or CEN in preventing muscle weight reduction during 28 days of simulated microgravity in rats

 

Muscle Fiber Types and Fiber CSA

The results from protocol 1 are depicted with the changes in relative wet weight of muscles in Fig. 1. After 28 days of HU, the mean CSAs of type I fibers of SOL, MG, LG, and EDL were 61%, 25%, 30%, and 35% less, respectively, than in CON rats (P < 0.05 or P < 0.01). The mean CSAs of type II fibers of SOL, MG, and LG were also reduced: 45%, 17%, and 19% less, respectively, than in CON rats (P < 0.05 or P < 0.01). HU for 28 days decreased the percentage of type I fibers in SOL and MG from 70% and 58% to 46% and 41%, respectively, whereas it had no significant effects on the percentage of type I fibers in LG and EDL (Fig. 1). Daily -Gx gravitation by STD resulted in a significant reduction in the shrinkage of type I and II fibers in SOL, MG, and LG and type I fiber in EDL. It also significantly reduced the decrease in the percentage of type I fibers in SOL and MG.



View larger version (38K):
[in this window]
[in a new window]
  		Fig. 1. Effectiveness of daily -Gx exposure of various durations by standing (STD) in preventing adverse changes in mean cross-sectional areas (CSA, µm2) of type I (A) and type II (B) fibers, proportion of type I fibers (C), and percent changes of absolute wet weight of soleus (SOL), medial gastrocnemius (MG), lateral gastrocnemius (LG), and extensor digitorum longus (EDL) muscles (D) of rats during 28 days of simulated microgravity. CON, control; SUS, tail suspension; SUS + STD1, 23 h SUS + 1 h STD; SUS + STD2, 22 h SUS + 2 h STD; SUS + STD4, 20 h SUS + 4 h STD. Values are means ± SE; n = 7. *P < 0.05; **P < 0.01 vs. CON; +P < 0.05; ++P < 0.01 vs. SUS.

 

Figure 2, in which results are presented from protocol 2, shows that after 28 days of HU the mean CSAs of type I fibers of SOL, MG, LG, and EDL were mostly affected, being 69%, 30%, 27%, and 25% less, respectively, than in CON rats (P < 0.05 or P < 0.01), and those of type II fibers were less affected, being 50%, 17%, and 20% less in SOL, MG, and LG, respectively, than in CON rats (P < 0.05 or P < 0.01). HU for 28 days also resulted in a significant decrease in the percentage of type I fibers in SOL and MG from 70% and 60% to 36% and 35%, respectively (P < 0.01). The efficacy of 1 h/day of periodic gravitation at 1 G (STD), 1.5 G (CEN), or 2.6 G (CEN) was related to the kind of muscle and the G level. For SOL and MG, the efficacy in maintaining the fiber size and fiber type composition was, in most cases, significantly decreased as the G level was increased from 1 to 2.6 G (Fig. 2, A–C). In EDL, CEN2.6G seemed to be more effective.



View larger version (37K):
[in this window]
[in a new window]
  		Fig. 2. Effectiveness of daily 1-h -Gx exposure, varying in G magnitude by standing (STD, 1 G) and centrifugation (CEN, >1 G) in preventing adverse changes in mean CSA (µm2) of type I (A) and type II (B) fibers, proportion of type I fibers (C), and percent changes of absolute wet weight of SOL, MG, LG, and EDL (D) of rats during 28 days of simulated microgravity. SUS + CEN1.5G, 23 h SUS + 1 h of 1.5 G CEN; SUS + CEN2.6G, 23 h SUS + 1 h of 2.6 G CEN. Values are means ± SE; n = 6. *P < 0.05; **P < 0.01 vs. CON; +P < 0.05; ++P < 0.01 vs. SUS.

 

Physical and Mechanical Properties of the Femur

Data from protocol 1 are listed in Table 5. After 28 days of HU, the wet, dry, and ash weights, diameter, and density of the femur were significantly decreased in SUS rats compared with CON rats (P < 0.01). Dry weight, ash weight, and diameter of the femur were also significantly lower in all the "SUS plus STD" groups than in the CON group (P < 0.01 or P < 0.05) but were significantly higher than in SUS rats in some cases (P < 0.01 or P < 0.05). The mechanical parameters, i.e., elastic load (Fe), maximum load (Fm), and bending rigidity coefficient (Cr), were significantly lower (P < 0.01) in SUS than in CON rats. Fe, Fm, and Cr were also significantly lower in SUS + STD than in CON rats (P < 0.05 or P < 0.01) but, in most cases, were significantly higher than in SUS rats (P < 0.01 or P < 0.05).


View this table:
[in this window]
[in a new window]
  		Table 5. Counteracting effects of daily STD in preventing adverse changes in femur during 28 days of simulated microgravity in rats

 

Data from protocol 2 are listed in Table 6. Two weight parameters and diameter and density of the femur were significantly lower in the SUS and the three countermeasure groups than in the CON group (P < 0.01); however, length of the femur was significantly greater in SUS and SUS + 1.5 G rats (P < 0.05). In most cases, there were no significant differences in these physical parameters between the SUS group and each of the three countermeasure groups. Fe, Fm, and Cr were significantly lower in the SUS group and the three countermeasure groups than in the CON group (P < 0.01), but, in most cases, these parameters were significantly higher in the countermeasure groups than in the SUS group (P < 0.01 or P < 0.05). However, there were no significant differences in physical and mechanical parameters among the three countermeasure groups of different G magnitude.


View this table:
[in this window]
[in a new window]
  		Table 6. Counteracting effects of daily STD or CEN in preventing adverse changes in femur during 28 days of simulated microgravity in rats

 

Cardiac Muscle Contractility

With respect to the general conditions of the animals from protocol 3, there were no significant differences between the CON and any of the other three experimental groups, except for the final body weight of the SUS + STD4 group, which was significantly less (P < 0.01) than the CON group (Table 7). However, 28 days of HU resulted in a significant weight loss in SOL of SUS rats, and daily STD had an obvious ameliorating effect on weight loss. Table 8 shows isometric myocardial contraction data. No significant differences were noted in resting tension or CSA of papillary muscles among the five groups. SUS for 28 days resulted in significant reductions in DT, peak rate of tension rise, and peak rate of tension decline compared with the CON rats (P < 0.05). The timing parameters, i.e., time to peak rate of tension rise and TPT, were significantly increased in SUS rats (P < 0.05). Daily -Gx gravitation by STD for 1, 2, or 4 h showed a significant effect in preventing the adverse changes in mechanical and timing parameters due to SUS alone (P < 0.01 or P < 0.05).


View this table:
[in this window]
[in a new window]
  		Table 7. Body weight and soleus, testis, and adrenal weights in CON, SUS, and SUS plus daily STD rats of protocol 3

 

View this table:
[in this window]
[in a new window]
  		Table 8. Changes in developed tension, maximal rate of tension change, and timing parameters of isometric contraction at Lmax of papillary muscles

 

Passive and active length-tension relations among the five groups are depicted in Fig. 3. No significant differences in resting length-tension relations were noted among the five groups. However, the curve describing the active length-tension relation of the papillary muscle of the SUS rats shifted significantly downward (P < 0.01) compared with the curves of the other four groups (P < 0.01). Further analysis showed no significant differences in DT at any muscle length among the CON and the three SUS + STD groups.



View larger version (24K):
[in this window]
[in a new window]
  		Fig. 3. Resting and developed tensions plotted as a function of length of papillary muscles of CON, SUS, and SUS + STD rats. Lmax, length associated with maximal force development. Values are means ± SE; n = 5–7. *P < 0.05; **P < 0.01 vs. CON.

 


   DISCUSSION
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
ACKNOWLEDGMENTS
 REFERENCES
 
The present study is an attempt to answer the following question: Do different physiological systems vary greatly in G requirement to maintain systems at normal terrestrial levels? The data indicate that the preventive value of daily short-duration -Gx gravitation is quite system specific. During 28 days of simulated microgravity, STD for 1 and 4 h/day was sufficient to prevent the adverse changes in the myocardium and SOL, respectively, whereas STD for 4 h/day could only ameliorate the adverse changes in the femur. Increase in G intensity to 2.6 G showed lessened prevention in the SOL and no additional prevention in the femur.

To titrate exclusively the effectiveness of periodic passive -Gx vector gravitations of different exposure durations and at different G levels, STD for 1, 2, or 4 h/day was used to provide periodic -1 Gx at 1 G and CEN at 1.5 or 2.6 G for 1 h/day was used to provide periodic -Gx hypergravitation at >1 G to SUS rats. In previous studies (11–13, 36, 41), STD ("stationary ground support" or "weight bearing") has been used because of its effectiveness in preventing muscle atrophy, but rarely osteopenia. CEN is the only choice allowing us to titrate the effectiveness of periodic -Gx hypergravitation at various G levels and has also been used in related studies (10, 11, 29, 30). During 28 days of HU, SUS alone did not affect the body weight gains of the rats, but SUS combined with various periodic gravitation treatments significantly decreased the final body weight gains in most cases. However, decreases in final body weight of treatment groups of protocol 1 were <10%. The reasons remain unclear. Restriction of movements in small tubelike cages during STD and reduced food consumption and more physical activity in treatment groups might be important factors. Although reduced final body weight gains in treatment groups suggest possible stressful influences of periodic gravitations, weights of the adrenals showed no significant differences among different experimental groups. Perhaps this kind of stress is insufficient to enlarge significantly the absolute adrenal mass (11) or induce only transient adrenal hypertrophy (30, 31, 42). The influence of daily short-duration hypergravitation on growth rate seems not to be a surprising result, because chronically centrifuged rats manifest signs and symptoms of stress, such as immobility, anorexia, and impaired thermoregulation, in the first few days and, finally, a decrease in growth rate and body mass (5, 11, 12, 30). Another disadvantage of using centrifugation to mimic IAG in animal studies is that the centrifuged rats usually assume a "rump-high crouching" posture (30), and the G forces imposed might not be transmitted via their limbs in a standing or walking posture (12). Another limitation of the present study is that measures were not taken to prevent cryptorchidism in the HU rats, which prevented collection of reliable data on the effectiveness of daily gravitation in preventing adverse changes in the testis (18). Despite these limitations, the main findings of the present study are most likely to be the consequence of intermittent -Gx gravity exposure on various physiological systems of HU rats.

Effectiveness of Daily Short-Duration -Gx Exposure by STD in Preventing Myocardial Contractility Depression Over 28 Days of HU

In the present study, as has been shown in our previous work (52, 55), 28 days of HU resulted in a significant reduction in DT and a significant prolongation in TPT of isolated papillary muscle. The present study showed for the first time that depression of myocardial contractility can be prevented by STD for 1 h/day over the 28 days of HU (Table 8). In the same study, 62%, 76%, and 89% of the left soleus wet weight was maintained by STD for 1, 2, and 4 h/day, respectively (Table 7).

Conflicting data have been reported for the effects of microgravity on cardiac mass and contractility. In most studies, decreased heart size during spaceflight observed by echocardiography was attributed primarily to reduced cardiac chamber volume and not loss of heart muscle. Also, indexes of cardiac contractility remain unchanged or increased slightly (for review see Refs. 7 and 47). However, evidence showing a loss of ventricular mass and a decrease in contractility of cardiac muscle in astronauts and bed-rest subjects has also been reported (2, 21, 28, 47). In D-2 astronauts and bed-rest subjects, marked reductions of 12% and 7.4%, respectively, in cardiac mass detected by magnetic resonance imaging (MRI) have been demonstrated (28). The atrophic change in cardiac muscle has been suggested as a nonneural mechanism (28, 54) accounting for postflight orthostatic intolerance. Conflicting data have also been reported in animal studies. Goldstein et al. (14) reported that the average cross-sectional area of fibers of left ventricular papillary muscle decreased significantly by 20% in rats flown on COSMOS 2044 for 14 days. Our previous work (52, 55) showed the nature and time course of depression in contractility of papillary muscle of rats subjected to 4 and 13 wk of tail suspension. Koenig et al. (25) demonstrated with invasively instrumented rhesus monkeys that, after 4 days of exposure to head-down tilt, the reduced orthostatic tolerance during graded lower body negative pressure was associated with a lowered cardiac contractility. Ray et al. (35) reported that 7 days of microgravity exposure and 7 or 28 days of HU did not reduce cardiac mass in rats. Additionally, simulated microgravity also had no effect on the peak rate of rise in left ventricular pressure. Reviewing the relevant work, they further indicated that reductions in cardiac mass might be related to relatively large reductions in body mass that occur in conjunction with the HU treatment. They further pointed out that when the reductions in body mass are relatively small (e.g., <10–12%), no change in cardiac mass occurs (35). Reductions in cardiac mass also paralleled the decrease in body mass due to chronic food restriction (17). In protocol 3 of the present study, the final body weights were comparable among CON, SUS, and the two treatment groups; the final body weight was 5.6% less in the SUS + STD4 group than in the CON group. Hence, the possible confounding influence of less gain in final body weight can be ruled out, although cardiac mass was not measured.

Despite the progress that has been made, whether hypovolemia and hypokinesia/hypodynamia during microgravity may lead to a reduction in cardiac mass and a decrement in performance (28, 52, 54) remains to be answered. To address these issues, methods with extremely good precision in measuring cardiac mass, such as MRI, should be considered in human studies (28). In animal studies, load-insensitive, inotropic state-sensitive index of cardiac contractility, such as Emax, the slope of the end-systolic pressure-volume relation (24, 37), and morphometric analysis (1) should be used to measure the cardiac performance and to quantitatively analyze the morphology of the myocardium, respectively. Reliable data and detailed information about central and ventricular hemodynamics during microgravity exposure also appear to be crucially important in understanding cardiac adaptation to microgravity (25, 28, 35, 47, 54). Nevertheless, the present study has provided data suggesting that intermittent gravitation might be a potential countermeasure to prevent myocardial changes if they occur due to microgravity.

Effectiveness of Daily Short-Duration -Gx Exposure by STD or CEN in Preventing Muscle Atrophy Over 28 Days of HU

In this study, as has been shown by others (16, 36), the relative effect of HU on muscle mass (based on wet weight) was as follows: slow extensors (SOL) > fast extensors (MG and LG) > fast flexors (EDL). The HU-induced changes in fiber CSAs of type I and II fibers and percentages of type I fibers in the four kinds of muscles showed a pattern similar, but not identical, to that of the absolute wet weight of respective muscles (Figs. 1 and 2), which corroborates previous studies on fiber-size and fiber-type changes in response to simulated microgravity in rats (12, 13, 36).

One important finding of the present study was that daily STD treatment significantly attenuated the atrophy of SOL, MG, LG, and EDL over 28 days of HU (Table 3, Fig. 1). According to the changes in most of the indexes of muscle atrophy, prolonging the exposure duration from 1 to 2 to 4 h/day showed a further atrophy-alleviating effect, with STD for 4 h/day being sufficient to maintain the muscle fiber CSAs, fiber type composition, and relative wet weight of all four muscles of suspended rats comparable to CON rats. However, with regard to the index of absolute wet weight, only SOL and MG showed complete prevention. Although the efficacy of STD had been reported by several groups (11–13, 36, 41), the present study titrated the efficacy of STD from 1 to 2 to 4 h/day, indicating clearly the duration dependency of the effectiveness of intermittent STD in attenuating HU-induced muscle atrophy. This duration dependency also supports the contention that the countermeasure effectiveness is due to the treatment. In similar work (15, 20, 22), despite a loss of initial body weight or no weight gain, the countermeasure effects were still manifest. It is apparent that this efficacy should also be related to the sustaining period of HU (12, 13). However, most of the pervious studies with a total of 40–60 min/day of STD as countermeasure were conducted over 7 days of HU (11, 15, 20, 22, 34). It has been shown that similar treatment was less effective over 14 days of HU than over 7 days of HU (48). In this context, Thomason et al. (41) showed that 2 or 4 h/day of stationary ground support for 4 wk significantly reduced the atrophic response of SOL, adductor longus, plantaris, and vastus lateralis, resulting in a sparing of myofibril protein and the relative and absolute slow myosin isoform contents of the SOL. The findings of the present study are consistent with those reported by Thomason et al. From the results of 7-day studies (11, 15, 20, 22, 34, 36), it could be speculated that much shorter periods of STD interspersed throughout the day would be more effective than one long daily period of STD of the same total duration. Another surprising finding is that a very short duration of STD with high-resistance intermittent exercise (high-load-bearing climbing) was more effective than STD alone in preventing the HU-induced atrophy of the SOL (22). In addition, the effectiveness of STD for 40 min/day alone (3, 48) or combined with resistance exercise (49) during 14 days of HU has also been examined and shown in single type I SOL fibers on the basis of their force-velocity-power and force-pCa relations.

Another important observation of this study was that as the magnitude of the daily 1-h gravitation increased from 1 G to 1.5 G to 2.6 G, the efficacy of alleviating muscle atrophy was markedly reduced in SOL and MG but increased in EDL (Table 4, Fig. 2). The design of protocol 2 was similar to that of D'Aunno et al. (10), except the latter was a 7-day study that was confined to SOL with muscle weight as the only index of atrophy. Their results are inconsistent with our results, in that they show no significant differences among 1 G (STD), 1.5 G, and 2.6 G (CEN) (10). This discrepancy might be related to the difference in the sustaining period of HU between the two studies.

Effectiveness of Daily Short-Duration -Gx Exposure by STD or CEN in Alleviating Bone Atrophy Over 28 Days of HU

The data in Table 5 clearly indicate that HU in rats for 28 days resulted in adverse changes in physical and mechanical parameters of the femur. The results corroborate previous studies on adverse changes in physical and mechanical properties of bone due to real/simulated microgravity (33). Among the physical parameters, the decreases in wet weight, diameter, and density of the femur were prevented by daily short-duration STD over 28 days of HU, whereas the decreases in dry weight, ash weight, and Fe, Fm, and Cr were only partially alleviated in most cases by daily STD. Two recent reports also favor the limited effectiveness of STD in preventing bone atrophy due to non-weight bearing. Jain et al. (23) showed that STD for 2 h/day resulted in prevention of wet weight loss (water content reduction) of the tibia but no improvement in ash weight and tibia calcium content reductions over 15 days of HU. They showed further that STD for 4 h/day was only partially successful in preventing the bone demineralization (23). In the suspended rats, 50% forelimb weight bearing was associated with bone loss in the humerus, which was not ameliorated by 2 h of full weight bearing daily over 35 days of HU (38).

Data from protocol 2 showed that 1, 1.5, or 2.6 G for 1 h/day significantly improved physical and mechanical parameters of the femur relative to SUS alone; however, all the data were still significantly lower than for CON rats (Table 6). Although there were no significant differences in physical and mechanical parameters examined among the three treatment groups, our unpublished histochemical and immunohistochemical findings further demonstrated that 1 G (STD) or 1.5 G (CEN) for 1 h/day appeared to be more effective than 2.6 G. The latter corroborates the results reported by Montufar-Solis et al. (29, 30), obtained from histomorphometric analysis of tibial growth plates, suggesting the possibility of a range of G that will maintain the normal growth and homeostasis of the bone. Finally, rats used in protocols 1 and 2 were of growing age, and their body weights were <400 g in protocol 1.

Comparison of Countermeasure Effectiveness of Daily -Gx Exposure Among Different Physiological Systems

Although previous work supports IAG as a potential countermeasure (40, 43–46), comprehensive studies over longer simulation periods are needed to further examine the physiological requirements for gravity of various physiological systems. If the requirements varied to a greater extent, it would appear to be inappropriate to consider IAG as an important protocol for future gravity-based countermeasures.

The present findings suggest that the physiological requirements for gravity may vary greatly among different organ systems. It is surprising that STD for 1 h/day was sufficient to prevent myocardial contractility depression and differential vasoreactivity changes in vessels (58) over 28 days of HU. On the other hand, STD for 4 h/day was effective in preventing mass reduction and histomorphometric changes in the SOL. However, the bone mass and mechanics were more resistant to such treatments, being partially alleviated by STD for 4 h/day over 28 days of HU. Further study is needed to determine whether daily short-duration gravitation combines with supplemental countermeasures, such as exercise and dynamic loading (26, 38), would be sufficient to prevent bone atrophy.

In contrast to human studies, our findings on myocardial contractility and vasoreactivity support the results obtained in a 4-day head-down bed-rest study (43, 44) that STD for 2 h/day completely prevented orthostatic intolerance after head-down bed rest. Our results on bone atrophy also support the possibility that STD for 2 or 4 h was only partially effective in alleviating increased calcium excretion. However, in the same study, walking for 2 or 4 h was more effective, indicating the importance of muscle activity and impact loading in maintaining bone density. With respect to the G level appropriate for IAG, Vil-Viliams et al. (46) pointed out that it should be close to 1 G (0.8–1.6 G), which can be well tolerated by most subjects. The present study and related work (10, 11, 29, 30) with rats also showed no additional benefit of increasing G level in preventing muscle and bone atrophy.

In conclusion, we are just starting to understand the physiological requirements of intermittent exposure to gravity in preventing adverse changes during real/simulated microgravity. In the present study, we demonstrated that the responsiveness of cardiac muscle, hindlimb muscle, and bone of HU rats to daily short-duration -Gx gravitation varies greatly. Therefore, comprehensive ground-based human and animal studies involving a multitude of physiological systems should be conducted to further evaluate the countermeasure effectiveness of intermittent gravity exposure on various tissues/organs (particularly bone loss) over longer periods of simulated microgravity.


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
REFERENCES
 
The authors thank Deng Jing-Mao for technical assistance.

This research was supported by National Natural Science Foundation of China Grant 30171032 and Defence Medical Fund Grants 98Z083 and 01Q114.

Preliminary results have been published as meeting proceedings (57).


   FOOTNOTES
 

Address for reprint requests and other correspondence: L.-F. Zhang, Dept. of Aerospace Physiology, Fourth Military Medical University, Xi'an 710032, People's Republic of China (E-mail: zhanglf{at}fmmu.edu.cn).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 

  1. Anversa P, Palackal T, Sonnenblick EH, Olivetti G, Meggs LG, and Capasso JM. Myocyte cell loss and myocyte cellular hyperplasia in the hypertrophied aging rat heart. Circ Res 67: 871-885, 1990.[Abstract/Free Full Text]
  2. Arbeille P and Herault S. Cardiac hemodynamics at rest and during LBNP after 4 days and 6 weeks in HDT. J Gravit Physiol 4: P31-P32, 1997.[Medline]
  3. Bangart JJ, Widrick JJ, and Fitts RH. Effect of intermittent weight bearing on soleus fiber force-velocity-power and force-pCa relationships. J Appl Physiol 82: 1905-1910, 1997.[Abstract/Free Full Text]
  4. Burton RR and Meeker LJ. Taking gravity into space. J Gravit Physiol 4: P17-P20, 1997.[Medline]
  5. Burton RR and Smith AH. Adaptation to acceleration environments. In: Handbook of Physiology. Environmental Physiology. Bethesda, MD: Am. Physiol. Soc., 1996, sect. 4, vol. II, chapt. 40, p. 943-970.
  6. Capasso JM, Strobeck JE, Malhotra A, Scheuer J, and Sonnenblick EH. Contractile behavior of rat myocardium after reversal of hypertensive hypertrophy. Am J Physiol Heart Circ Physiol 242: H882-H888, 1982.[Abstract/Free Full Text]
  7. Charles JB, Frey MA, Fritsch-Yelle JM, and Fortner GW. Cardiovascular and cardiorespiratory function. In: Space Biology and Medicine. Humans in Spaceflight, edited by Huntoon CSL, Antipov VV, and Grigoriev AI. Reston, VA: Am. Inst. Aeronaut. Astronaut., 1996, book 1, p. 63-88.
  8. Chen J, Zhang LF, Han C, Yu GS, and Ma J. Modulation of myocardial {alpha}1- but not {beta}-adrenoceptors after 90-day tail-suspension. J Gravit Physiol 3: 57-62, 1996.[Medline]
  9. Convertino VA. Exercise as a countermeasure for physiological adaptation to prolonged spaceflight. Med Sci Sports Exerc 28: 999-1014, 1996.[ISI][Medline]
  10. D'Aunno DS, Thomason DB, and Booth FW. Centrifugal intensity and duration as countermeasures to soleus muscle atrophy. J Appl Physiol 69: 1387-1389, 1990.[Abstract/Free Full Text]
  11. D'Aunno DS, Robinson RR, Smith GS, Thomason DB, and Booth FW. Intermittent acceleration as a countermeasure to soleus muscle atrophy. J Appl Physiol 72: 428-433, 1992.[Abstract/Free Full Text]
  12. Edgerton R and Roy RR. Neuromuscular adaptations to actual and simulated spaceflight. In: Handbook of Physiology. Enviromental Physiology. Bethesda, MD: Am. Physiol. Soc., 1996, sect. 4, vol. II, chapt. 32, p. 721-763.
  13. Fitts RH, Riley DR, and Widrick JJ. Microgravity and skeletal muscle. J Appl Physiol 89: 823-839, 2000.[Abstract/Free Full Text]
  14. Goldstein MA, Edwards RJ, and Schroeter JP. Cardiac morphology after conditions of microgravity during COSMOS 2044. J Appl Physiol 73 Suppl: 94S-100S, 1992.
  15. Graham SC, Roy RR, Hauschka EO, and Edgerton VR. Effects of periodic weight support on medial gastrocnemius fibers of suspended rats. J Appl Physiol 67: 945-953 1989.[Abstract/Free Full Text]
  16. Grindeland RE, Roy RR, Edgerton VR, Grossman EJ, Mukku VR, Jiang B, Pierotti DJ, and Rudolph I. Interactive effects of growth hormone and exercise on muscle mass in suspended rats. Am J Physiol Regul Integr Comp Physiol 267: R316-R322, 1994.[Abstract/Free Full Text]
  17. Haddad F, Bodell PW, McCue SA, Herrick RE, and Baldwin KM. Food restriction-induced transformations in cardiac functional and biochemical properties in rats. J Appl Physiol 74: 606-612, 1993.[Abstract/Free Full Text]
  18. Hadley JA, Hall JC, O'Brien A, and Ball R. Effects of a simulated microgravity model on cell structure and function in rat testis and epididymis. J Appl Physiol 72: 748-759, 1992.[Abstract/Free Full Text]
  19. Hargens AR and Watenpaugh DE. Cardiovascular adaptation to spaceflight. Med Sci Sports Exerc 28: 977-982, 1996.[ISI][Medline]
  20. Hauschka EO, Roy RR, and Edgerton VR. Periodic weight support effects on rat soleus fibers after hindlimb suspension. J Appl Physiol 65: 1231-1237, 1988.[Abstract/Free Full Text]
  21. Henry WL, Epstein SE, Griffith JM, Goldstein RT, and Redwood DR. Effect of prolonged spaceflight on cardiac function and dimensions. In: Biomedical Results From Skylab, edited by Johnston RS and Dietlein LF. Washington, DC: NASA, 1977, p. 366-371.
  22. Herbert ME, Roy RR, and Edgerton VR. Influence of one-week hindlimb suspension and intermittent high load exercise on rat muscles. Exp Neurol 102: 190-198, 1988.[ISI][Medline]
  23. Jain PK, Iyer EM, Banerjee PK, and Banerjee NS. Modification of bone atrophy by daily 2 hour weight support during simulated weightlessness in rats. Ind J Aerosp Med 41: 22-25, 1997.
  24. Kawada T, Sunagawa K, and Sato T. An implantable multichannel microtelemetry system for small animals (Abstract). Aviat Space Environ Med 72: 280, 2001.
  25. Koenig SC, Convertino VA, Fanton JW, Reister CA, Gaffney FA, Ludwig DA, Krotov VP, Trambovetsky EV, and Latham RD. Evidence for increased cardiac compliance during exposure to simulated microgravity. Am J Physiol Regul Integr Comp Physiol 275: R1343-R1352, 1998.[Abstract/Free Full Text]
  26. Kreitenberg A, Baldwin KM, Bagian JP, Cotten S, Witmer J, and Caiozzo VJ. The "space cycle" self-powered human centrifuge: a proposed countermeasure for prolonged human spaceflight. Aviat Space Environ Med 69: 66-72, 1998.[Medline]
  27. Lacker JR and DiZio P. Artificial gravity as a countermeasure in long-duration spaceflight. J Neurosci Res 62: 169-176, 2000.[ISI][Medline]
  28. Levine BD, Zuckerman JH, and Pawelczyk JA. Cardiac atrophy after bed-rest deconditioning: a nonneural mechanism for orthostatic intolerance. Circulation 96: 517-525, 1997.[Abstract/Free Full Text]
  29. Montufar-Solis D, Duke PJ, and D'Aunno D. In vivo and in vitro studies of cartilage differentiation in altered gravities. Adv Space Res 17: 193-199, 1996.[Medline]
  30. Montufar-Solis D and Duke PJ. Gravitational changes affect tibial growth plates according to Hert's curve. Aviat Space Environ Med 70: 245-249, 1999.[Medline]
  31. Morey-Holton ER and Globus RK. Hindlimb unloading rodent model: technical aspects. J Appl Physiol 92: 1367-1377, 2002.[Abstract/Free Full Text]
  32. Nwoye L, Mommaerts WF, Simpson DR, Seraydarian K, and Marusich M. Evidence for a direct action of thyroid hormone in specifying muscle properties. Am J Physiol Regul Integr Comp Physiol 242: R401-R408, 1982.[Abstract/Free Full Text]
  33. Oganov VS and Schneider VS. Skeletal system. In: Humans in Spaceflight, edited by Huntoon CSL, Antipov VV, and Grigoriev. Reston, VA: Am. Inst. Aeronaut. Astronaut., 1996, book I, p. 247-266.
  34. Pierotti DJ, Roy RR, Flores V, and Edgerton VR. Influence of 7 days of hindlimb suspension and intermittent weight support on rat muscle mechanical properties. Aviat Space Environ Med 61: 205-210, 1990.[Medline]
  35. Ray CA, Vasques M, Miller TA, Wilkerson MK, and Delp MD. Effect of short-term microgravity and long-term hindlimb unloading on rat cardiac mass and function. J Appl Physiol 91: 1207-1213, 2001.[Abstract/Free Full Text]
  36. Roy RR, Baldwin KM, and Edgerton VR. The plasticity of skeletal muscle: effects of neuromuscular activity. Exerc Sport Sci Rev 19: 269-312, 1991.[Medline]
  37. Sagawa K, Suga H, Shoukas AA, and Bakalar KM. Endsystolic pressure/volume ratio: a new index of ventricular contractility. Am J Cardiol 40: 748-753, 1977.[ISI][Medline]
  38. Schultheis L, Ruff CB, Rastogi S, Bloomfield S, Hogan HA, Fedarko N, Thierry-Palmer M, Ruiz J, Bauss F, and Shapiro JR. Disuse bone loss in hindquarter-suspended rats: partial weight-bearing, exercise and ibandronate treatment as countermeasures. J Gravit Physiol 7: P13-P14, 2000.[Medline]
  39. Shipov AA. Artificial gravity. In: Space Biology and Medicine: Humans in Spaceflight. Reston, VA: Am. Inst. Aeronaut. Astronaut., 1996, book 2, p. 349-363.
  40. Shulzhenko EB and Vil-Viliams IF. Short-radius centrifuge as a method in long-term space flights. Physiologist 35: S122-S125, 1992.[Medline]
  41. Thomason DB, Herrick RE, and Baldwin KM. Activity influences on soleus muscle myosin during rodent hindlimb suspension. J Appl Physiol 63: 138-144, 1987.[Abstract/Free Full Text]
  42. Thomason DB, Herrick RE, Surdyka D, and Baldwin KM. Time course of soleus muscle myosin expression during hindlimb suspension and recovery. J Appl Physiol 63: 130-137, 1987.[Abstract/Free Full Text]
  43. Vernikos J. Artificial gravity: intermittent centrifugation as a space flight countermeasure. J Gravit Physiol 4: P13-P16, 1997.[Medline]
  44. Vernikos J, Ludwig DA, Ertl AC, Wade CE, Keil L, and O'Hara D. Effect of standing or walking on physiological changes induced by head-down bed rest: implications for spaceflight. Aviat Space Environ Med 67: 1069-1079, 1996.[Medline]
  45. Vil-Viliams IF, Kotovskaya AR, and Shipov AA. Biomedical aspects of artificial gravity. J Gravit Physiol 4: P27-P28, 1997.[Medline]
  46. Vil-Viliams IF, Kotovskaya AR, Nikolashin GF, and Lukjanuk VJ. Modern view on the short-arm centrifuge as a potential generator of artificial gravity in piloted missions. J Gravit Physiol 8: P145-P146, 2001.[Medline]
  47. Watenpaugh DE and Hargens AR. The cardiovascular system in microgravity. In: Handbook of Physiology. Environmental Physiology. Bethesda, MD: Am. Physiol. Soc., 1996, sect. 4, vol. I, chapt. 29, p. 631-674.
  48. Widrick JJ, Bangart JJ, Karhanek M, and Fitts RH. Soleus fiber force and maximal shortening velocity after nonweight bearing with intermittent activity. J Appl Physiol 80: 981-987, 1996.[Abstract/Free Full Text]
  49. Widrick JJ and Fitts RH. Peak force and maximal shortening velocity of soleus fibers after non-weight-bearing and resistance exercise. J Appl Physiol 82: 189-195, 1997.[Abstract/Free Full Text]
  50. Wronski TJ and Morey-Holton ER. Skeletal response to simulated weightlessness: a comparison of suspension techniques. Aviat Space Environ Med 58: 63-68, 1987.[Medline]
  51. Young LR. Artificial gravity considerations for a Mars exploration mission. Ann NY Acad Sci 871: 367-378, 1999.[Abstract/Free Full Text]
  52. Yu ZB, Zhang LF, and Chen J. Time course of contractility depression in simulated weightlessness rats and its reversibility. Chin J Aerosp Med 5: 138-142, 1994.
  53. Zhang LF. Vascular adaptation to microgravity: what have we learned? J Appl Physiol 91: 2415-2430, 2001.[Abstract/Free Full Text]
  54. Zhang LF, Yu ZB, Ma J, and Mao QW. Peripheral effector mechanism hypothesis of postflight cardiovascular dysfunction. Aviat Space Environ Med 72: 567-575, 2001.[Medline]
  55. Zhang LF, Yu ZB, and Ma J. Functional alterations in cardiac muscle after medium- or long-term simulated weightlessness and related cellular mechanisms. J Gravit Physiol 2: P5-P8, 1995.[Medline]
  56. Zhang LF. Biomedical problems of artificial gravity: overview and challenge. Space Med Med Eng 14: 70-74, 2001.
  57. Zhang LF. Microgravity-induced cardiovascular deconditioning: peripheral effector mechanism hypothesis and gravity-based countermeasure. J Gravit Physiol 7: 135-136, 2000.
  58. Zhang LN, Gao F, Ma J, and Zhang LF. Daily head-up tilt, standing, or centrifugation can prevent vasoreactivity changes in arteries of simulated weightlessness rats. J Gravit Physiol 7: 143-144, 2000.



This article has been cited by other articles:


Home page
 DiabetesHome page
M. T. Hamilton, D. G. Hamilton, and T. W. Zderic
Role of Low Energy Expenditure and Sitting in Obesity, Metabolic Syndrome, Type 2 Diabetes, and Cardiovascular Disease
Diabetes, November 1, 2007; 56(11): 2655 - 2667.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J.-H. Xue, L.-F. Zhang, J. Ma, and M.-J. Xie
Differential regulation of L-type Ca2+ channels in cerebral and mesenteric arteries after simulated microgravity in rats and its intervention by standing
Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H691 - H701.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
B. Sun, L.-F. Zhang, F. Gao, X.-W. Ma, M.-L. Zhang, J. Liu, L.-N. Zhang, and J. Ma
Daily short-period gravitation can prevent functional and structural changes in arteries of simulated microgravity rats
J Appl Physiol, September 1, 2004; 97(3): 1022 - 1031.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow