Although spaceflight and bed rest are known to cause muscular atrophy in the antigravity muscles of the legs, the changes in sympathetic and cardiovascular responses to exercises using the atrophied muscles remain unknown. We hypothesized that bed rest would augment sympathetic responses to isometric exercise using antigravity leg muscles in humans. Ten healthy male volunteers were subjected to 14-day 6° head-down bed rest. Before and after bed rest, they performed isometric exercises using leg (plantar flexion) and forearm (handgrip) muscles, followed by 2-min postexercise muscle ischemia (PEMI) that continues to stimulate the muscle metaboreflex. These exercises were sustained to fatigue. We measured muscle sympathetic nerve activity (MSNA) in the contralateral resting leg by microneurography. In both pre- and post-bed-rest exercise tests, exercise intensities were set at 30 and 70% of the maximum voluntary force measured before bed rest. Bed rest attenuated the increase in MSNA in response to fatiguing plantar flexion by ∼70% at both exercise intensities (both P < 0.05 vs. before bed rest) and reduced the maximal voluntary force of plantar flexion by 15%. In contrast, bed rest did not alter the increase in MSNA response to fatiguing handgrip and had no effects on the maximal voluntary force of handgrip. Although PEMI sustained MSNA activation before bed rest in all trials, bed rest entirely eliminated the PEMI-induced increase in MSNA in leg exercises but partially attenuated it in forearm exercises. These results do not support our hypothesis but indicate that bed rest causes a reduction in isometric exercise-induced sympathetic activation in (probably atrophied) antigravity leg muscles.
- autonomic nervous system
- muscle atrophy
- sympathetic nerve activity
exposures to spaceflight (11, 25) and its simulation model, 6° head-down bed rest (6, 8, 9), are known to cause cardiovascular deconditioning in humans. Although the primary symptom of the deconditioning is orthostatic intolerance on return to Earth (2, 6, 25), deconditioning may also include a reduction in sympathetic and cardiovascular responses to isometric exercise (15, 21). For example, bed rest attenuates the increase in arterial pressure and heart rate in response to static handgrip exercise (15, 21). While some studies suggest that these responses are reduced after spaceflight (179-389 days) (21), a more recent study on the effects of spaceflight (16 days) failed to confirm this observation (7). However, most of these studies investigated exercises using forearm muscles that were not affected by spaceflight and bed rest.
Contrary to the situation of forearm muscles, exposure to spaceflight and bed rest causes muscular atrophy in the antigravity muscles of the legs (3, 5, 17). This is associated with various changes in muscular tissues, including decreases in myofiber size (3, 5, 17), capillary volume (3, 4), mitochondrial volume density (4), and muscle oxidative capacity (3-5). Although astronauts in space and hospitalized patients confined to bed must use their atrophied antigravity leg muscles on return to daily life, particularly in standing and walking, little is known regarding changes in the sympathetic and cardiovascular responses to exercise using these atrophied leg muscles after spaceflight and bed rest. These changes may relate to the integrative physiological effects of microgravity on human cardiovascular and musculoskeletal systems.
In our earlier study (8), we found that 14-day bed rest did not change muscle sympathetic nerve activity (MSNA) during isometric forearm exercise (handgrip) but mildly reduced MSNA during postexercise muscle ischemia (PEMI) that continues to stimulate the muscle metaboreflex (16, 20). Because the muscle metaboreflex activation is due to muscle metabolic responses (16, 20), it is likely that the reflex is more activated in antigravity atrophied leg muscles that would elicit a greater disturbance in metabolic responses to exercises (3, 5). Accordingly, we hypothesized that bed rest would augment sympathetic responses to isometric exercise using antigravity leg muscles in humans. We subjected 10 healthy male volunteers to a 14-day period of bed rest. Bed rest is known to induce an ∼10% reduction in maximal voluntary contraction (MVC) of antigravity leg muscles but does not affect forearm muscles (3). We performed isometric fatiguing exercises with leg (plantar flexion) and forearm (handgrip) muscles, followed by 2 min of PEMI, with measuring MSNA in the contralateral resting leg by the microneurographic technique.
MATERIALS AND METHODS
Ten healthy male volunteers with a mean age (±SE) of 22 ± 1 yr, mean height (±SE) of 168 ± 2 cm, and mean weight (±SE) of 64 ± 3 kg participated in this study. We evaluated all subjects as healthy by completing a detailed medical history and by conducting a physical examination, resting electrocardiogram, blood chemistry analyses, and psychological testing. None of the subjects smoked or had experience of recreational drugs. All subjects were righthanded. All subjects gave informed consent to participate in this study, which was approved by the Ethical Committee of the National Space Development Agency of Japan and the Committee of Human Research, Research Institute of Environmental Medicine, Nagoya University.
The volunteers were subjected to 14 days of 6° head-down bed rest. The experimental bed-rest room was air-conditioned at a temperature of 25-26°C and relative humidity of 30-40%. Physical exercise and drinking of caffeinated and alcoholic beverages were prohibited throughout the bed-rest period. During bed rest, staff nurses continuously monitored subjects to ensure that they remained in the 6° head-down position and performed no physical exercise. Dietary intake was restricted to between 2,000 and 2,100 kcal/day (55% carbohydrate, 25% fat, 20% protein), including ∼3,000 mg/day of sodium. Fluid intake from daily drinks was ad libitum, and the average was 1,261 ± 83 ml/day. The light-dark cycle was 16 h of light and 8 h of darkness with lights on at 0700.
Experimental Protocol of Forearm and Leg Isometric Exercise Tests
Tests before bed rest. Two to three weeks before bed rest, we conducted pre-bed-rest forearm and leg exercise tests. We instructed the subjects to refrain from eating for 3 h before the experiments. Each subject was positioned horizontally supine on a bed equipped with a plate containing a strain-gauge transducer (LP-200KB, WGA-710A-4, Kyowa Electronic Instruments, Tokyo, Japan) for the measurement of contraction force generated in the right leg. We fixed the ankle and the metatarsal head of the right foot to this plate using nonelastic strips, setting the ankle at an angle of 90°. The elbow of the right arm was almost fully extended. We placed a handgrip dynamometer (Digital Grip Dynamometer, Takei Kiki Kogyo, Japan) on the right hand for each subject to grip. Each subject performed brief (<5 s) muscle contraction exercises four times: two handgrips and two plantar flexions, with all his strength. Each contraction was done separately, with intervals of at least 10 min between contractions. The average values of the two handgrips and plantar flexions were used as the MVC forces for the forearm and leg exercises, respectively.
After these exercises, each subject remained supine and rested for >30 min. At least 20 min after a satisfactory recording site for microneurography (the tibial nerve at the left popliteal fossa) was found, we obtained preexercise baseline measurements of the variables over a period of 5 min. The subjects then performed isometric exercises of right handgrip (forearm exercise test) and right plantar flexion (leg exercise test) separately, sustaining the contraction to the point of fatigue. In both forearm and leg exercises, we set two levels of contraction intensity: 30 and 70% of the MVC forces. Forearm and leg exercise tests were performed alternately at intervals of at least 20 min. In forearm or leg exercise, 30 and 70% MVC exercises were done in random order. We used an oscilloscope to display to the exercising subject the target force and the achieved output from a handgrip dynamometer or foot plate transducer. When the achieved output declined to <85% of the target force for >2 s, we inflated the arterial pressure cuff around the right upper arm (for forearm exercise) or the right thigh (for leg exercise) to a suprasystolic arterial pressure of 230 mmHg with a lag of 3 s and terminated the exercise after 3 s. This produced PEMI and was sustained for 2 min. The PEMI was intended to trap muscle metabolites and thereby continue stimulating the muscle metaboreflex to maintain the MSNA (16, 20). During all exercise tests, we regulated the subject's breathing using a metronome (Digital Metronome MA-20, Korg, Tokyo). We required the subjects to breathe 15 times/min with expiration and inspiration phases of 2 s each. We also required them to avoid breathing deeply or to perform Valsalva maneuvers. In addition, we directed them to avoid contracting other limbs. We measured the variables continuously during the preexercise control period, exercise, PEMI, and recovery.
Tests after bed rest. Immediately after the bed-rest period, we conducted post-bed-rest forearm and leg exercise tests. Subjects were positioned horizontally supine on the bed. We determined MVC forces of handgrip and plantar flexion in the same manner as before bed rest. We also performed forearm and leg exercise tests in an identical manner to those before bed rest. All exercise tests after bed rest were conducted at the same intensities as before bed rest (30 and 70% of the MVC force obtained before, and not after, bed rest). As a result, in the leg exercise tests, the exercise intensity was similar in absolute terms but higher in relative terms after bed rest than before bed rest, because bed rest decreased the MVC force of plantar flexion. In contrast, in the forearm exercise tests, the exercise intensity was similar in both relative and absolute terms before and after bed rest, because bed rest did not change the MVC force of handgrip.
Measurements. MSNA was measured from the tibial nerve of the left resting leg as reported previously (12, 24). Briefly, a tungsten microelectrode (model 26-05-1, Haer, Bowdoinham, ME) was inserted percutaneously into the muscle nerve fascicles of the tibial nerve at the left popliteal fossa without anesthesia. Nerve signals were fed into a preamplifier (Kohno Instruments, Nagoya, Japan) with two active band-pass filters set between 500 and 5,000 Hz and were subsequently monitored with a loudspeaker. MSNA was identified according to the following discharge characteristics: 1) arterial pulse synchronous spontaneous efferent discharges, 2) afferent activity induced by tapping of calf muscles but not in response to gentle skin touch, and 3) enhancement during phase II of the Valsalva maneuver. We stored the MSNA signals on a DAT recorder (PC216Ax, Sony Magnescale) at a sampling rate of 12,000 Hz, together with other cardiovascular variables.
We measured arterial pressure continuously with a pneumatic finger cuff on the left arm with periodical calibrating (Portapres, TNO Institute of Applied Physics Biomedical Instrumentation) (26). The mean arterial pressure was calculated as the diastolic arterial pressure plus one-third of the pulse pressure. In a preliminary experiment without bed rest, we compared the Portapres finger pressure with simultaneously measured right brachial arterial pressure (BP203MII, Nippon Colin) every minute during leg exercises (plantar flexion at 30 and 70% of MVC, n = 6). In the experiment, every 1-min mean finger pressure was identical to every corresponding 1-min mean brachial pressure (r =0.97, P < 0.05), verifying that the Portapres finger pressure accurately reflects arterial pressure.
A 20-gauge intravenous catheter was inserted into the antecubital vein in the left forearm. Venous blood samples were obtained for determination of plasma lactate concentration before baseline, at rest, and during the 3rd min of the recovery period for each trial.
Data analysis. The full-wave rectified MSNA signal was fed through a resistance-capacitance low-pass filter at a time constant of 0.1 s to obtain the mean voltage neurogram. This was then resampled at 1,000 Hz together with other cardiovascular variables. MSNA bursts were identified and their areas calculated using a computer program custom built by our laboratory. MSNA was expressed as both the rate of integrated activity per minute (burst rate) and the total activity, by integrating individual burst area per minute (total MSNA). Because the burst area and hence the total MSNA were dependent on electrode position, they were expressed as an arbitrary unit (AU) that was normalized by the individual control value before exercise (an average total MSNA per minute during 5 min of preexercise rest was given an arbitrary value of 100). The burst area of each burst during experimental procedures was normalized to this value.
Heart rate was determined from the electrocardiogram. Values of MSNA (burst rate and total activity), mean arterial pressure, heart rate, and respiratory rate were averaged for each 5 min of preexercise baseline. Values were also averaged for the appropriate periods in each exercise test in accordance with the duration sustained to fatigue. For the variables during exercise, the values were averaged every minute for 70% MVC leg exercise (in Fig. 2, Ex 1 and Ex 2 indicate mean values for 0-60 s and 61-120 s, respectively, of exercise) and 30% MVC forearm exercise. The values during exercise were also averaged every 5 min for 30% MVC leg exercise, and every 30 s for 70% MVC forearm exercise (in Fig. 3, Ex 1 and Ex 2 indicate mean values for 0-30 s and 31-60 s, respectively, of exercise). Value at the point of fatigue was the average for the last 20 s of exercise. The average values for the last 60 s of PEMI and recovery were also calculated.
Data are expressed as means ± SE. Repeated-measures ANOVA was used to compare variables for condition (before and after bed rest) and time [baseline, exercise 1 (first half), exercise 2 (second half), fatigue, PEMI, and recovery]. When the main effect or interaction term was found to be significant, post hoc comparisons were made using the Scheffé's F-procedure. A Wilcoxon signed-rank test was used to compare variables (MVC forces of handgrip and plantar flexion and greatest circumferences of the forearm and the calf) before and after bed rest. We considered P < 0.05 to be statistically significant.
Bed rest did not change the strength of MVC force of handgrip (411.7 ± 27.1 N before bed rest and 408.3 ± 29.4 N after) but reduced that of plantar flexion from 861.7 ± 43.0 to 755.2 ± 42.8 N (P < 0.05). Bed rest did not change the maximal circumference length of the forearm (26.1 ± 0.8 cm before and 25.9 ± 0.8 cm after) but reduced that of the calf from 36.2 ± 0.8 to 34.1 ± 0.7 cm (P < 0.05). Bed rest did not change baseline MSNA burst rate, heart rate, or mean arterial pressure (see Figs. 2 and 3).
Leg exercise test (plantar flexion). At 70% MVC, the duration of leg exercise sustained to the point of fatigue was 151 ± 9 s before bed rest and 147 ± 8 s after bed rest. Figure 1 illustrates a representative microneurographic recording of MSNA in a typical subject performing 70% MVC leg exercise. Although leg exercise and the subsequent PEMI strongly increased MSNA before bed rest, these increases were attenuated markedly after bed rest. The average data of all subjects showed that although leg exercise increased MSNA both before and after bed rest, the increase was markedly reduced after bed rest (P < 0.05 vs. before bed rest, Fig. 2). Before bed rest, PEMI decreased MSNA (P < 0.05 vs. end of the exercise) but maintained it at an elevated level relative to the preexercise baseline. After bed rest, however, PEMI failed to maintain the MSNA, resulting in a return to the baseline level (Fig. 2). These results indicated that bed rest abolished the PEMI-induced increases in MSNA after leg exercise.
In 70% MVC leg exercise, the effects of bed rest on mean arterial pressure during leg exercise and PEMI were consistent with those for MSNA (Fig. 2). Although leg exercise increased mean arterial pressure both before and after bed rest, the increase was smaller after bed rest (P < 0.05 vs. before bed rest, Fig. 2). PEMI decreased mean arterial pressure (P < 0.05 vs. end of the exercise) but maintained it above the baseline level (P < 0.05 vs. baseline) before bed rest, whereas the pressure returned to base-line after bed rest (Fig. 2). Bed rest did not significantly affect heart rate during leg exercise (Fig. 2). Both before and after bed rest, respiratory rate was almost constant at 15 cycles/min throughout rest, leg exercise, PEMI, and recovery. Leg exercise at 70% MVC increased plasma lactate concentration similarly before and after bed rest (from 1.0 ± 0.1 to 2.7 ± 0.1 mmol/ml before bed rest and 0.9 ± 0.1 to 2.8 ± 0.1 mmol/ml after bed rest).
The effects of bed rest on MSNA, mean arterial pressure, and heart rate in 30% MVC leg exercise were similar to those observed in 70% MVC leg exercise. The duration of exercise sustained to the point of fatigue was similar before (684 ± 18 s) and after (673 ± 18 s) bed rest. Bed rest attenuated MSNA during the first 10 min of exercise and at fatigue both in burst rate (from 34 ± 2 to 21 ± 2 bursts/min, P < 0.05) and total activity [from 363 ± 321 to 166 ± 17 AU, P < 0.05]. Although PEMI maintained the elevated MSNA burst rate (14 ± 3 bursts/min) and total activity (227 ± 29 AU) above baseline before bed rest, the PEMI-induced elevation of MSNA disappeared after bed rest. Similarly, PEMI-induced increases in mean arterial pressure seen before bed rest (24 ± 2 mmHg) were abolished after bed rest. Bed rest did not affect responses of heart rate and respiratory rate. Leg exercise at 30% MVC increased plasma lactate concentration similarly before and after bed rest (from 0.9 ± 0.1 and 2.9 ± 0.1 mmol/ml before bed rest and 0.8 ± 0.1 to 2.9 ± 0.1 mmol/ml after bed rest).
Forearm exercise test (handgrip). The duration of exercise sustained to fatigue was similar before and after bed rest in forearm exercise at 70% (77 ± 9 and 75 ± 7 s, before and after bed rest, respectively) and 30% MVC (153 ± 11 and 147 ± 9 s). In contrast to leg exercises, forearm exercise increased MSNA and mean arterial pressure similarly before and after bed rest both at 30 and 70% MVC (Fig. 3). PEMI maintained MSNA at elevated levels above baseline before and after bed rest (P < 0.05 vs. baseline); however, the increases during PEMI were reduced after bed rest at 30% MVC (from 241 ± 32 to 150 ± 29 AU) and 70% MVC (Fig. 3) (P < 0.05 at both intensities). PEMI-induced increase in mean arterial pressure was also lower after bed rest in forearm exercise at 30% (from 22 ± 3 to 10 ± 3 mmHg) and 70% MVC (Fig. 3) (P < 0.05 at both intensities). Bed rest did not affect heart rate during forearm exercise (Fig. 3). Both before and after bed rest, respiratory rate was almost constant at 15 cycles/min throughout rest, forearm exercise, PEMI, and recovery. Forearm exercises increased plasma lactate concentration similarly before and after bed rest, at both 30% (from 0.9 ± 0.1 to 3.1 ± 0.1 mmol/ml before bed rest; from 0.8 ± 0.1 to 3.2 ± 0.1 mmol/ml after bed rest) and 70% MVC (from 1.0 ± 0.1 to 2.8 ± 0.1 mmol/ml before bed rest; from 0.9 ± 0.1 to 2.9 ± 0.1 mmol/ml after bed rest).
Reduced MSNA and Pressor Responses to Antigravity Leg Exercise After Bed Rest
Although spaceflight and bed rest are known to cause muscular atrophy in antigravity muscles in legs, changes in sympathetic and cardiovascular responses to exercise using the atrophied muscles remain unknown. Given a possible greater disturbance in metabolic response to exercise in atrophied muscles, we hypothesized that bed rest would augment sympathetic responses to isometric exercise using antigravity leg muscles in humans. The new finding of the present study is that 14-day bed rest attenuated MSNA and pressor responses to fatiguing isometric plantar flexion by ∼70% and reduced the MVC force of plantar flexion by 15%. In contrast, bed rest did not alter MSNA and pressor responses to fatiguing isometric handgrip and had no effect on the MVC force of handgrip, which are consistent with previous studies (7, 8). These results do not support our hypothesis. They indicate that bed rest causes a reduction in isometric exercise-induced sympathetic activation in (probably atrophied) antigravity leg muscles.
The most likely mechanism responsible for the attenuated MSNA responses to isometric exercise in antigravity leg muscles after bed rest is the absence or strong reduction of activation of the muscle metaboreflex. The muscle metaboreflex is known to play a primary role in MSNA response to exercise (14, 16, 20). We assessed the reflex during PEMI because this method traps muscle metabolites in muscles that have undergone exercise and continues to stimulate the muscle metaboreflex but not other reflexes (such as the muscle mechanoreflex, central command) (14, 16, 20). Our present pre-bed-rest data confirmed the importance of the reflex because MSNA remained elevated from the preexercise level during PEMI. However, of special note is the fact that the sustained increase in MSNA by PEMI disappeared after bed rest (Fig. 2). This result indicates that bed rest almost abolishes the activation of the muscle metaboreflex in antigravity leg muscles.
Our data showed that heart rate responses to leg exercises did not change after bed rest despite the attenuated increases in MSNA. It was possible that cardiac vagal responses to exercise might be augmented after bed rest, compensating for the reduced cardiac sympathetic neural responses and resulting in normal heart rate responses.
We do not consider the attenuated MSNA and pressor responses to exercises observed in this study as simple accommodations to the tests. In preliminary experiments, we repeated exercise tests with identical protocols to the present study (n = 6; 30 and 70% MVC handgrip, 30 and 70% MVC plantar flexion) with an interval of 2 wk of non-bed-rest period. We confirmed the reproducibility of sympathetic and cardiovascular responses because these responses were almost identical between the first and second trials with a correlation coefficient of ∼0.9.
Comparison of forearm and antigravity leg exercises. Bed rest exerts different effects on forearm and antigravity leg muscles in MSNA and pressor responses to fatiguing isometric exercise. First, activation of the muscle metaboreflex was only mildly reduced in forearm muscles, in contrast to entire disappearance in antigravity leg muscles. MSNA and pressor responses during PEMI were ∼50% lower after bed rest in handgrip exercises both at 30 and 70% of MVC, consistent with our earlier studies using 30% MVC handgrip (8). Although the reduction of the muscle metaboreflex in handgrip was not observed in the NeuroLab (STS-90) space shuttle mission study (7), this could be explained by the methodological difference of spaceflight vs. bed rest.
Second, total responses of MSNA and arterial pressure to fatiguing isometric handgrip in forearm muscles were preserved after bed rest, in contrast to the greatly attenuated responses in antigravity leg muscles. Our finding of forearm exercises was consistent with the results of earlier studies of bed rest (8, 23) and also a recent study from NeuroLab (STS-90) space shuttle mission (7). However, our finding of forearm exercises disagreed with earlier studies by Spaak et al. (21) and Pagani et al. (15) that showed the reduced heart rate and arterial pressure responses to handgrip at 25-30% MVC. The discrepancy may be explained by the difference in the exercise mode: handgrip sustained to fatigue in our study vs. handgrip for fixed durations in their studies (2 and 5 min). An important point is that sympathetic activation during static handgrip directly relates to the development of fatigue (18, 19) and peaks at fatigue (19). Therefore, their methodology of fixed exercise duration may limit and complicate the interpretation of data. Because, generally, muscle strength (MVC) does not equate to endurance, it may not predict well the activation of muscle metaboreflex during exercise. Another factor is the duration of spaceflight or bed rest. Compared with the present study (14 days), longer term bed rest [42 days (15) and 120 days (21) days] and spaceflight (179-389 days) (21) were conducted in their studies. Long- and short-term exposures to microgravity could have different effects on sympathetic and cardiovascular responses to exercise.
Mechanisms for Reduced Activations of the Muscle Metaboreflex After Bed Rest
Again, our results of MSNA and pressor responses during PEMI showed that bed rest abolished the activation of muscle metaboreflex in antigravity leg muscles and mildly attenuated the activation in forearm muscles. However, it is difficult to determine which mechanism in the reflex circuit is responsible for the difference in muscle metaboreflex activation. We propose several possibilities. The first possibility is altered central modulation related to immobilization during bed rest. Bed rest did not change maximal handgrip force and thus is unlikely to have deconditioned forearm muscles. However, the activation of muscle metaboreflex was smaller after bed rest even in the forearm muscles. Accordingly, factors other than muscles, particularly changes in central processing in relation to immobilization, could be responsible in part for the reduced activation of the muscle metaboreflex. This postulation might explain why a recent space shuttle mission study reported by NeuroLab (STS-90) failed to observe reduced MSNA during PEMI (7) because astronauts are highly active in the space shuttle whereas the subjects in our bed-rest study were clearly immobilized. In addition, this explanation could relate to the interesting earlier finding that muscle metaboreceptor responses are attenuated in heart failure patients (22) who are likely to be immobilized or restricted in daily life activities compared with healthy persons.
The second possibility is changes in muscle afferent sensitivity in atrophied leg muscles after bed rest. Given the total disappearance of muscle metaboreflex activation in antigravity leg muscles compared with partial reduction in forearm muscles, factors specific to antigravity muscles could contribute to the reduced activation in muscle metaboreflex. Muscular atrophy (deconditioning) is an obvious possibility. Changes in muscle afferent sensitivity in atrophied muscles rather than alterations in metabolic factors could be responsible for the reduced activation of muscle metaboreflex, because accumulation of exercise-induced metabolites might be increased rather than decreased in atrophied muscles. Indeed, our data showed that bed rest did not reduce plasma lactate concentrations in leg exercises. Accordingly, we speculate that the sensitivity and/or number of metabosensitive receptors on afferent fibers (group III and IV) (20) is reduced in antigravity atrophied leg muscles after bed rest. In addition to decreases in myofiber size (3, 5, 17) and capillary volume (3, 4) in muscular tissues, muscular atrophy is accompanied by reduced muscle spindle afferent sensitivity in soleus muscle after hindlimb suspension in rats (rodent model of microgravity) (1). Unfortunately, little is known regarding changes in metabosensitive muscle afferent fibers in atrophied muscles. Further studies are required to investigate this possibility.
Hypoperfusion to contracting muscles may not account for the reduced activation of muscle metaboreflex in forearm and leg muscles after bed rest. In a previous study, 14-day bed rest reduced resting blood flow to upper and lower limbs (10) and thus could reduce perfusion to exercising limb muscles. However, this would not be responsible for our findings because hypoperfusion induced by arm elevation increased, instead of decreased, MSNA activation during PEMI after isometric handgrip (13).
In severe clinical conditions including pelvis and femur bone fracture, spinal cord injury, and severe cardiac failure, hospitalized patients are confined to bed for several weeks. Because the bed rest often decreases muscular performance particularly in antigravity leg muscles, exercise has been conducted in hospitals to improve muscular performance as post-bed-rest rehabilitation. However, little attention has been given to the accompanying sympathetic and pressor responses to the exercises in deconditioned or atrophied muscles, even though greater sympathetic excitation is a substrate for cardiovascular events, including ventricular arrhythmia and stroke. Our finding suggests that post-bed-rest rehabilitation has a minor risk of enhanced sympathetic excitation because MSNA responses to exercise in antigravity leg muscles are reduced, rather than increased, after bed rest.
Fourteen-day bed rest is known to cause muscular atrophy in antigravity leg muscles (3, 5, 17). Our 14-day bed rest reduced the MVC force of plantar flexion by 15% and the maximal circumference length of the calf by 2.1 cm. Accordingly, we presume that the antigravity calf muscles might be atrophied by bed rest. However, we lack direct evidence of muscular atrophy. We found no earlier fatigue (3, 5) or greater metabolic response to the leg isometric exercise. Leg circumference changes could be affected by fluid shifts (6), whereas muscle strength changes could be influenced by neuromotor change. Further histochemical and morphological investigations on muscular atrophy are required in studies assessing cardiovascular deconditioning after microgravity.
In conclusion, 14-day bed rest attenuated MSNA and pressor responses during the fatiguing exercise and PEMI periods strongly when the isometric contractions were performed by the legs (plantar flexion) but mildly and only during the PEMI periods when performed by the forearm (handgrip). The bed rest reduced the MVC force of plantar flexion but not that of handgrip. These results indicate that bed rest causes a reduction in isometric exercise-induced sympathetic activation in (probably atrophied) antigravity leg muscles.
This study was conducted as a part of “Ground Research Announcement for Space Utilization” promoted by the Japan Space Forum. The study was supported by Grant-in-Aid for Scientific Research (grant no. 13770032) from the Ministry of Education, Science, Sport, and Culture of Japan.
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