Force-velocity-power and force-pCa relationships of human soleus fibers after 17days of bed rest

Soleus musclefibers from the rat display a reduction in peak power andCa²⁺ sensitivity after hindlimbsuspension. To examine human responses to non-weight bearing, weobtained soleus biopsies from eight adult men before and immediatelyafter 17 days of bed rest (BR). Single chemically skinned fibers weremounted between a force transducer and a servo-controlled positionmotor and activated with maximal (isotonic properties) and/orsubmaximal (Ca²⁺ sensitivity)levels of free Ca²⁺. Gelelectrophoresis indicated that all pre- and post-BR fibers expressedtype I myosin heavy chain. Post-BR fibers obtained from one subjectdisplayed increases in peak power andCa²⁺ sensitivity. In contrast,post-BR fibers obtained from the seven remaining subjects showed anaverage 11% reduction in peak power (P < 0.05), with each individualdisplaying a 7-27% reduction in this variable. Post-BR fibersfrom these subjects were smaller in diameter and produced 21% lessforce at the shortening velocity associated with peak power. However,the shortening velocity at peak power output was elevated 13% in thepost-BR fibers, which partially compensated for their lower force.Post-BR fibers from these same seven subjects also displayed a reducedsensitivity to free Ca²⁺(P < 0.05). These results indicatethat the reduced functional capacity of human lower limb extensormuscles after BR may be in part caused by alterations in thecross-bridge mechanisms of contraction.

     

Maximal and submaximal forces of slow fibers in human soleus after bed rest.

The effects of 2 and 4 mo of bed rest, with or without exercise countermeasures, on the contractile properties of slow fibers in the human soleus muscle were examined. Mean fiber diameters were 8 and 36% smaller after 2 and 4 mo of bed rest, respectively, than the pre-bed rest level. Maximum tetanic force (P(o)), maximum activated force (F(max)) per cross-sectional area (CSA), and the common-logarithm value of free Ca(2+) concentration required for half-maximal activation (pCa(50)) also decreased after 2 and 4 mo of bed rest. In contrast, maximum unloaded shortening velocity (V(o)) was increased after 2 and 4 mo of bed rest. After 1 mo of recovery, fiber diameters, P(o), F(max) per CSA (P > 0.05), and pCa(50) were increased and V(o) decreased toward pre-bed rest levels. Effects of knee extension/flexion exercise by wearing an anti-G Penguin suit for 10 h daily, and the effects of loading or unloading of the plantar flexors with (Penguin-1) or without (Penguin-2) placing the elastic loading elements of the suit, respectively, were investigated during ~2 mo of bed rest. In the Penguin-1 group, mean fiber diameter, P(o), F(max) per CSA, V(o), and pCa(50) were similar before and after bed rest. However, the responses of fiber size and contractile properties to bed rest were not prevented in the Penguin-2 group, although the degree of the changes was less than those induced by bed rest without any countermeasure. These results indicate that long-term bed rest results in reductions of fiber size, force-generation capacity, and Ca(2+) sensitivity, and enhancement of shortening velocity in slow fibers of the soleus. The data indicate that continuous mechanical loading on muscle, such as stretching of muscle, is an effective countermeasure for the prevention of muscular adaptations to gravitational unloading.     

Effect of P(i) on unloaded shortening velocity of slow and fast mammalian muscle fibers

Chemically skinned muscle fibers,prepared from the rat medial gastrocnemius and soleus, were subjectedto four sequential slack tests in Ca²⁺-activating solutionscontaining 0, 15, 30, and 0 mM added P_i. P_i (15 and 30 mM) had no effect on the unloaded shortening velocity (V_o) of fibers expressing type IIb myosin heavychain (MHC). For fibers expressing type I MHC, 15 mM P_i didnot alter V_o, whereas 30 mM P_ireduced V_o to 81 ± 1% of the original 0 mM P_i value. This effect was readily reversible whenP_i was lowered back to 0 mM. These results are notcompatible with current cross-bridge models, developed exclusively fromdata obtained from fast fibers, in which V_o isindependent of P_i. The response of the type I fibers at 30 mM P_i is most likely the result of increased internal drag opposing fiber shortening resulting from fiber type-specific effects ofP_i on cross bridges, the thin filament, or therate-limiting step of the cross-bridge cycle.

     

Effects of 17 days bed rest on the maximal isometric torque of the flexors and extensors of the ankle

Researchers examined the extent to which short-term bed rest affects maximal isometric force produced by the plantar and dorsal flexors of the ankle. Results indicate an increase in average values of maximal isometric torque throughout the study, a significant increase in isometric EMG between control and bed rest subjects, and a significant isometric EMG augmentation in bed rest subjects by the end of the study. The effects of training on maximal isometric torque and muscle function impairment are discussed.     

Effects of 17 days of head-down bed rest on hydro-electrolytic regulation in men

Prolonged periods of head-down bed rest (HDBR) are commonly used to mimic the effects of microgravity. HDBR has been shown to produce, as in space, a cephalad redistribution of circulating blood volume with an increase in central blood volume which induces the early adaptations in blood volume regulating hormones. Changes in atrial natriuretic peptide (ANP), arginine vasopressin (AVP), renin activity and aldosterone have been observed. Many reports describe these endocrine adaptations but few investigations of rhythms are in the literature. We proposed to evaluate the circadian rhythms of the hormones and electrolytes involved in the hydro-electrolytic regulation during a HDBR study which was designed to simulate a 17-day spaceflight (Life and Microgravity Spacelab experiment, LMS, NASA).     

Resistance training of long duration modulates force and unloaded shortening velocity of single muscle fibres of young women

The aim of the present study was to clarify the impact of long term (1 year) resistance training (RT) on structure and function of single muscle fibres of vastus lateralis in young female subjects. Five young women (age: 25.4 ± 6.2 year) performed exercise sessions at 60% of single subject own repetition maximum (1 RM) 1 h twice a week. Maximum voluntary force was determined pre- and post-RT and was found to significantly increase post-RT ensuring a successful impact of RT on muscle performance in vivo. Needle muscle biopsy samples were obtained both pre- and post-RT and the following determinations were performed: myosin heavy chain isoform (MHC) distribution of the whole muscle samples by SDS–PAGE; cross sectional area (CSA), specific force (Po/CSA) and maximum shortening velocity (Vo) of a large population (n = 358) of single skinned muscle fibres classified on the basis of MHC isoform composition by SDS–PAGE. The results suggest that the long duration of RT can determine a significant increase in specific force (Po/CSA) and unloaded shortening velocity (Vo) of single muscle fibres in female subjects, whereas no muscle fibre hypertrophy and no shift in MHC isoform content was observed.     

Human soleus single muscle fiber function with exercise or nutrition countermeasures during 60 days of bed rest

The soleus muscle has been consistently shown to atrophy more than other leg muscles during unloading and is difficult to protect using various exercise countermeasure paradigms. However, the efficacy of aerobic exercise, a known stimulus for oxidative adaptations, has not been tested in combination with resistance exercise (RE), a known hypertrophic stimulus. We hypothesized that a concurrent exercise program (AE + RE) would preserve soleus fiber myosin heavy chain (MHC) I size and function during 60 days of bed rest. A secondary objective was to test the hypothesis that a leucine-enriched high protein diet would partially protect soleus single fiber characteristics. Soleus muscle biopsies were obtained before and after bed rest from a control (BR; n = 7), nutrition (BRN; n = 8), and exercise (BRE; n = 6) group. Single muscle fiber diameter (Dia), peak force (Po), contractile velocity, and power were studied. BR decreased (P < 0.05) MHC I Dia (-14%), Po (-38%), and power (-39%) with no change in contractile velocity. Changes in MHC I size (-13%) and contractile function (approximately 30%) from BRN were similar to BR. BRE decreased (P < 0.05) MHC I Dia (-13%) and Po (-23%), while contractile velocity increased (P < 0.05) 26% and maintained power. These soleus muscle data show 1) the AE + RE exercise program maintained MHC I power but not size and strength, and 2) the nutrition countermeasure did not benefit single fiber size and contractile function. The divergent response in size and functional MHC I soleus properties with the concurrent exercise program was a unique finding further highlighting the challenges of protecting the unloaded soleus.     

Effects of 20 days bed rest on muscle morphology

Using ultrasound, muscle thickness and fascicle angles from aponeurosis were evaluated before, during and after 20 days bed rest (BR). Subjects were healthy adults (4 women and 4 men). Measurements were carried out before and after BR and after 10 weeks of recovery, respectively. Muscle measurements were taken at nine sites in trunk and upper and lower extremities, respectively. For the m. triceps brachii, m. vastus lateralis, and m. gastrocnemius medialis, fascicle angles from the aponeurosis as well as muscle thickness were measured. There was a high statistical significant correlation between muscle thickness and cross-sectional area for quadriceps muscles, suggesting applicability of muscle thickness for evaluation of muscle size. Muscle thickness decreased in muscles of the lower extremity by 2.1-4.4 % after bed rest. In triceps brachii and vastus lateralis muscles, there were no prominent changes in muscle thickness and fascicle angles. It was concluded that muscle morphology deteriorates with changes in muscle architecture by bed rest but the response is small and muscle-specific. It was also suggested that bed rest affects not only muscle mass but muscle tone as well.     

Detrimental effects of reloading recovery on force, shortening velocity, and power of soleus muscles from hindlimb-unloaded rats

To better understand how atrophied muscles recover from prolonged nonweight-bearing, we studied soleus muscles (in vitro at optimal length) from female rats subjected to normal weight bearing (WB), 15 days of hindlimb unloading (HU), or 15 days HU followed by 9 days of weight bearing reloading (HU-R). HU reduced peak tetanic force (P(o)), increased maximal shortening velocity (V(max)), and lowered peak power/muscle volume. Nine days of reloading failed to improve P(o), while depressing V(max) and intrinsic power below WB levels. These functional changes appeared intracellular in origin as HU-induced reductions in soleus mass, fiber cross-sectional area, and physiological cross-sectional area were partially or completely restored by reloading. We calculated that HU-induced reductions in soleus fiber length were of sufficient magnitude to overextend sarcomeres onto the descending limb of their length-tension relationship upon the resumption of WB activity. In conclusion, the force, shortening velocity, and power deficits observed after 9 days of reloading are consistent with contraction-induced damage to the soleus. HU-induced reductions in fiber length indicate that sarcomere hyperextension upon the resumption of weight-bearing activity may be an important mechanism underlying this response.     

Cardiorespiratory responses to physical work during and following 17 days of bed rest and spaceflight.

To determine the influence of a 17-day exposure to real and simulated spaceflight (SF) on cardiorespiratory function during exercise, four male crewmembers of the STS-78 space shuttle flight and eight male volunteers were studied before, during, and after the 17-day mission and 17 days of -6 degrees head-down-tilt bed rest (BR), respectively. Measurements of oxygen uptake, pulmonary ventilation, and heart rate were made during submaximal cycling 60, 30, and 15 days before the SF liftoff and 12 and 7 days before BR; on SF days 2, 8, and 13 and on BR days 2, 8, and 13; and on days 1, 4, 5, and 8 after return to Earth and on days 3 and 7 after BR. During 15 days before liftoff, day 4 after return, and day 8 after return and all BR testing, each subject completed a continuous exercise test to volitional exhaustion on a semirecumbent (SF) or supine (BR) cycle ergometer to determine the submaximal and maximal cardiorespiratory responses to exercise. The remaining days of the SF testing were limited to a workload corresponding to 85% of the peak pre-SF peak oxygen uptake (Vo2 peak) workload. Exposure to and recovery from SF and BR induced similar responses to submaximal exercise at 150 W. Vo2 peak decreased by 10.4% from pre-SF (15 days before liftoff) to day 4 after return and 6.6% from pre-BR to day 3 after return, which was partially (SF: -5.2%) or fully (BR) restored within 1 wk of recovery. Workload corresponding to 85% of the peak pre-SF Vo2 peak showed a rapid and continued decline throughout the flight (SF day 2, -6.2%; SF day 8, -9.0%), reaching a nadir of -11.3% during testing on SF day 13. During BR, Vo2 peak also showed a decline from pre-BR (BR day 2, -7.3%; BR day 8, -7.1%; BR day 13, -9.0%). These results suggest that the onset of and recovery from real and simulated microgravity-induced cardiorespiratory deconditioning is relatively rapid, and head-down-tilt BR appears to be an appropriate model of this effect, both during and after SF.     

Effects of passive tension on unloaded shortening speed of frog single muscle fibers.

Experiments were performed to determine the influence of sarcomere length and passive tension on the velocity of unloaded shortening (Vu) as measured by the slack test technique. Slack test results were obtained from intact twitch fibers isolated from the frog (Rana temporaria). Measurements were made both in the absence and presence of passive tension using two different protocols. In one, all releases were initiated from the same sarcomere length and passive tension level; in the other, all releases ended at the same sarcomere length. In the absence of passive tension, no difference was observed between the results from the two slack test protocols. When passive tension was present, performing all releases from the same initial sarcomere length and passive tension level resulted in linear step size-slack time relationships in which the slopes (Vu) were independent of length over a sarcomere length range extending to 3.1 microns, and the intercepts increased with increasing sarcomere length. Performing all releases to the same final sarcomere length in the presence of passive tension produced nonlinear step size-slack time relationships. The results presented here show that, in the presence of significant levels of passive tension, the traditional interpretation of the slope of the slack test plot as the constant unloaded shortening velocity is only correct when all length steps are initiated from the same initial sarcomere length and level of passive tension.     

Effect of an ADP analog on isometric force and ATPase activity of active muscle fibers

The role played by ADP in modulatingcross-bridge function has been difficult to study, because it is hardto buffer ADP concentration in skinned muscle preparations. To solvethis, we used an analog of ADP, spin-labeled ADP (SL-ADP). SL-ADP bindstightly to myosin but is a very poor substrate for creatine kinase orpyruvate kinase. Thus ATP can be regenerated, allowing well-definedconcentrations of both ATP and SL-ADP. We measured isometric ATPaserate and isometric tension as a function of both [SL-ADP], 0.1-2mM, and [ATP], 0.05-0.5 mM, in skinned rabbit psoas muscle,simulating fresh or fatigued states. Saturating levels of SL-ADPincreased isometric tension (by P'), the absolute value of P' beingnearly constant, ~0.04 N/mm², in variable ATP levels, pH7. Tension decreased (50-60%) at pH 6, but upon addition ofSL-ADP, P' was still ~0.04 N/mm². The ATPase wasinhibited competitively by SL-ADP with an inhibition constant,K_i, of ~240 and 280 µM at pH 7 and 6, respectively. Isometric force and ATPase activity could both be fit bya simple model of cross-bridge kinetics.

     

Myonuclear domain and myosin phenotype in human soleus after bed rest with or without loading.

After 2 or 4 mo of bed rest (6 degrees head-down tilt) and 1 mo of ambulation, there was a tendency toward a higher percentage of fibers expressing fast myosin heavy chain (MHC) isoforms and a de novo appearance of fibers coexpressing type I+IIa+IIx and IIa+IIx MHC in human soleus fibers. After 2 and 4 mo of bed rest, the mean size of type I fibers decreased by 12 (P > 0.05) and 39%, respectively. Because myonuclear number/mm of fiber length was unchanged, myonuclear domain was smaller after bed rest than before. The mean size and myonuclear domain of type I fibers were largest after 1 mo of recovery. The effects of wearing an antigravity device (Penguin suit), which had a modest but continuous resistance at the knee and ankle (Penguin-1) or knee resistance without loading on the ankle (Penguin-2), for 10 consecutive h/day were determined during 2 mo of bed rest. Mean fiber sizes in Penguin-1, but not Penguin-2, group were maintained at or above pre-bed-rest levels, whereas neither group showed phenotype changes. Myonuclear domain in type I fibers was larger in Penguin-1 and smaller in Penguin-2 group post- compared with pre-bed rest, indicating that a single daily 10-h bout of modest muscle loading can prevent bed-rest-induced soleus fiber atrophy but has minimal effect on myosin phenotype. The specific adaptive cellular strategies involved may be a function of the duration and magnitude of the adaptive stimulus as well as the immediate activity history of the fiber before the newly changed functional demands.     

Effects of long-duration bed rest on structural compartments of m. soleus in man

Magnetic resonance imaging (MRI), histomorphometry and electron microscopy of muscle demonstrate that long-term exposure to actual or simulated weightlessness (including head down bed rest) leads to decreased volume of antigravity muscles in mammals. In muscles interbundle space is occupied by the connective tissue. Rat studies show that hindlimb unloading induces muscle fiber atrophy along with increase in muscle non-fiber connective tissue compartment. Beside that, usually 20% of the muscle fiber volume is comprised by non-contractile (non-myofibrillar) compartment. The aim of the present study was to compare changes in muscle volume, and in muscle fiber size with alterations in myofibrillar apparatus, and in connective tissue compartment in human m. soleus under conditions of 120 day long head down bed rest (HDBR).     

Effects of five days of bed rest with intermittent centrifugation on neurovestibular function

Objectives:

We tested whether intermittent short-radius centrifugation was effective for mitigating alteration in balance and gait following bed rest.

Methods:

Ten male subjects were exposed to 5 days of 6° head-down tilt bed rest with: (a) no countermeasure; (b) daily 1-g centrifugation for a continuous 30-min period; and (c) daily 1-g centrifugation for six periods of 5 min. During and after the bed rest, subjects were asked to scale the severity of neurovestibular symptoms that followed centrifugation or 80º head-up tilt. Following the bed rest, equilibrium scores were derived from anterior-posterior sway while standing on a foam pad with the eyes open or closed while making pitch head movements, and gait was evaluated by grading subjects’ performance during various locomotion tasks.

Results:

At the beginning of bed rest, one single 30-min period of centrifugation induced more severe neurovestibular symptoms than six periods of 5-min centrifugation. After bed rest, although equilibrium scores and gait performance were not significantly altered, subjects felt less neurovestibular dysfunction with orthostatic stress when centrifugation was used.

Conclusion:

Centrifugation was effective at reducing the severity of neurovestibular symptoms after bed rest, but this decrease was not different between one or multiple daily sessions.     

Effects of 18 days of bed rest on leg and arm venous properties.

Venous function may be altered by bed rest deconditioning. Yet the contribution of altered venous compliance to the orthostatic intolerance observed after bed rest is uncertain. The purpose of this study was to assess the effect of 18 days of bed rest on leg and arm (respectively large and small change in gravitational gradients and use patterns) venous properties. We hypothesized that the magnitude of these venous changes would be related to orthostatic intolerance. Eleven healthy subjects (10 men, 1 woman) participated in the study. Before (pre) and after (post) 18 days of 6 degrees head-down tilt bed rest, strain gauge venous occlusion plethysmography was used to assess limb venous vascular characteristics. Leg venous compliance was significantly decreased after bed rest (pre: 0.048 +/- 0.007 ml x 100 ml(-1) x mmHg(-1), post: 0.033 +/- 0.007 ml x 100 ml(-1) x mmHg(-1); P < 0.01), whereas arm compliance did not change. Leg venous flow resistance increased significantly after bed rest (pre: 1.73 +/- 1.08 mmHg x ml(-1) x 100 ml x min, post: 3.10 +/- 1.00 mmHg x ml(-1) x 100 ml x min; P < 0.05). Maximal lower body negative pressure tolerance, which was expressed as cumulative stress index (pressure x time), decreased in all subjects after bed rest (pre: 932 mmHg x min, post: 747 mmHg x min). The decrease in orthostatic tolerance was not related to changes in leg venous compliance. In conclusion, this study demonstrates that after bed rest, leg venous compliance is reduced and leg venous outflow resistance is enhanced. However, these changes are not related to measures of orthostatic tolerance; therefore, alterations in venous compliance do not to play a major role in orthostatic intolerance after 18 days of head-down tilt bed rest.     

Changes in muscle size and architecture following 20 days of bed rest

Five healthy men carried out a program of head-down bed rest (BR) for 20 days. Before and after BR, a series of cross-sectional scans of the thigh were performed using magnetic resonance imaging, from which volumes of the quadriceps muscles were determined and physiological cross-sectional areas (PCSA) were calculated. Muscle thickness and pennation angles of the triceps brachii, vastus lateralis, and triceps surae muscles were also determined by ultrasonography. During BR, subjects performed unilateral isokinetic knee extension exercises every day. The contralateral limb served as a control. Decrease in PCSA after BR was greater in the control (-10.2 +/- 6.3%) than in the trained limb (-5.2 +/- 4.2%). Among the quadriceps, vastus intermedius in the control limb was predominantly atrophied by BR with respect to the volume and PCSA, and the rectus femoris showed the greatest training effect and retained its size in the trained limb. Decreases in muscle thicknesses in leg muscles were not prevented by the present exercise protocol, suggesting a need for specific exercise training for these muscles. Neither trained nor control muscles showed significant changes in pennation angles in any muscles after BR, suggesting that muscle architecture does not change remarkably by muscle atrophy by up to 10%.