Cardiac atrophy after bed rest and spaceflight.

Cardiac muscle adapts well to changes in loading conditions. For example, left ventricular (LV) hypertrophy may be induced physiologically (via exercise training) or pathologically (via hypertension or valvular heart disease). If hypertension is treated, LV hypertrophy regresses, suggesting a sensitivity to LV work. However, whether physical inactivity in nonathletic populations causes adaptive changes in LV mass or even frank atrophy is not clear. We exposed previously sedentary men to 6 (n = 5) and 12 (n = 3) wk of horizontal bed rest. LV and right ventricular (RV) mass and end-diastolic volume were measured using cine magnetic resonance imaging (MRI) at 2, 6, and 12 wk of bed rest; five healthy men were also studied before and after at least 6 wk of routine daily activities as controls. In addition, four astronauts were exposed to the complete elimination of hydrostatic gradients during a spaceflight of 10 days. During bed rest, LV mass decreased by 8.0 +/- 2.2% (P = 0.005) after 6 wk with an additional atrophy of 7.6 +/- 2.3% in the subjects who remained in bed for 12 wk; there was no change in LV mass for the control subjects (153.0 +/- 12.2 vs. 153.4 +/- 12.1 g, P = 0.81). Mean wall thickness decreased (4 +/- 2.5%, P = 0.01) after 6 wk of bed rest associated with the decrease in LV mass, suggesting a physiological remodeling with respect to altered load. LV end-diastolic volume decreased by 14 +/- 1.7% (P = 0.002) after 2 wk of bed rest and changed minimally thereafter. After 6 wk of bed rest, RV free wall mass decreased by 10 +/- 2.7% (P = 0.06) and RV end-diastolic volume by 16 +/- 7.9% (P = 0.06). After spaceflight, LV mass decreased by 12 +/- 6.9% (P = 0.07). In conclusion, cardiac atrophy occurs during prolonged (6 wk) horizontal bed rest and may also occur after short-term spaceflight. We suggest that cardiac atrophy is due to a physiological adaptation to reduced myocardial load and work in real or simulated microgravity and demonstrates the plasticity of cardiac muscle under different loading conditions.     

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.     

Molecular aspects of stress-gene regulation during spaceflight

Spaceflight-associated stress has been the topic of investigation since the first terrestrial organisms were exposed to this unique environment. Organisms that evolved under the selection pressures of earth-normal environments can perceive spaceflight as a stress, either directly because gravity influences an intrinsic biological process, or indirectly because of secondary effects imparted by spaceflight upon environmental conditions. Different organisms and even different organs within an organism adapt to a spaceflight environment with a diversity of tactics. Plants are keenly sensitive to gravity for directed development, and are also sensitive to other stresses associated with closed-system spaceflight environments. Within the past decade, the tools of molecular biology have begun to provide a sophisticated evaluation of spaceflight-associated stress and the genetic responses that accompany metabolic adaptation to spaceflight.     

Muscle atrophy and hormonal regulation in women in 120 day bed rest

It is known, that exposures to real and simulated weightlessness results in pronounced reduction of the cross-sectional area (CSA) of slow-twitch(ST) and fast-twitch(FT) fibers of mammalian muscle. After space flights of various durations, head-down tilt bedrest, and 7-days of dry immersion sufficient [correction of isufficient] reductions of CSA of both fiber types were observed in man and in the majority of these cases the atrophy levels of ST and FT fibers were similar. It is well-known, that elevated contractile activities of muscle system attenuate muscle atrophy development. It remains still unclear which fiber type is more susceptible to training effects. Among physiological mechanisms involved in the process of microgravity-induced atrophy development which are supposed to be the most important are the profound decrease of a mechanical tension of muscle fibers in situ and alterations in hormonal control of muscle protein metabolism. But it is not known yet if the hormonal changes in the course of exposure to gravitational unloading match somehow the time-course of muscle fiber size reduction. The aim of the study was to investigate the time-course of muscle fiber atrophy development and changes in plasma hormone levels in the course of long-duration BR with and without high-intensity locomotor interval physical training.     

Effects of normobaric hypoxic bed rest on the thermal comfort zone

Future Lunar and Mars habitats will maintain a hypobaric hypoxic environment to minimise the risk of decompression sickness during the preparation for extra-vehicular activity. This study was part of a larger study investigating the separate and combined effects of inactivity associated with reduced gravity and hypoxia, on the cardiovascular, musculoskeletal, neurohumoural, and thermoregulatory systems. Eleven healthy normothermic young male subjects participated in three trials conducted on separate occasions: (1) Normobaric hypoxic ambulatory confinement, (2) Normobaric hypoxic bedrest and (3) Normobaric normoxic bedrest. Normobaric hypoxia was achieved by reduction of the oxygen fraction in the air (F_iO₂=0.141±0.004) within the facility, while the effects of reduced gravity were simulated by confining the subjects to a horizontal position in bed, with all daily routines performed in this position for 21 days. The present study investigated the effect of the interventions on behavioural temperature regulation. The characteristics of the thermal comfort zone (TCZ) were assessed by a water-perfused suit, with the subjects instructed to regulate the sinusoidally varying temperature of the suit within a range considered as thermally comfortable. Measurements were performed 5 days prior to the intervention (D-5), and on days 10 (D10) and 20 (D20) of the intervention. no statistically significant differences were found in any of the characteristics of the TCZ between the interventions (HAMB, HBR and NBR), or between different measurement days (D-5, D10, D20) within each intervention. rectal temperature remained stable, whereas skin temperature (T_sk) increased during all interventions throughout the one hour trial. no difference in T_sk between D-5, D10 and D20, and between HAMB, HBR and NBR were revealed. subjects perceived the regulated temperature as thermally comfortable, and neutral or warm. we conclude that regulation of thermal comfort is not compromised by hypoxic inactivity.     

Lung function during and after prolonged head-down bed rest.

We determined the effects of prolonged head-down tilt bed rest (HDT) on lung mechanics and gas exchange. Six subjects were studied in supine and upright postures before (control), during [day 113 (D113)], and after (R + number of days of recovery) 120 days of HDT. Peak expiratory flow (PF) never differed between positions at any time and never differed from controls. Maximal midexpiratory flow (FEF(25-75%)) was lower in the supine than in the upright posture before HDT and was reduced in the supine posture by about 20% between baseline and D113, R + 0, and R + 3. The diffusing capacity for carbon monoxide corrected to a standardized alveolar volume (volume-corrected DL(CO)) was lower in the upright than in the supine posture and decreased in both postures by 20% between baseline and R + 0 and by 15% between baseline and R + 15. Pulmonary blood flow (Q(C)) increased from R + 0 to R + 3 by 20 (supine) and 35% (upright). As PF is mostly effort dependent, our data speak against major respiratory muscle deconditioning after 120 days of HDT. The decrease in FEF(25-75%) suggests a reduction in elastic recoil. Time courses of volume-corrected DL(CO) and Q(C) could be explained by a decrease in central blood volume during and immediately after HDT.     

Unilateral lower limb suspension does not mimic bed rest or spaceflight effects on human muscle fiber function.

We used Ca2+-activated skinned muscle fibers to test the hypothesis that unilateral lower leg suspension (ULLS) alters cross-bridge mechanisms of muscle contraction. Soleus and gastrocnemius biopsies were obtained from eight subjects before ULLS, immediately after 12 days of ULLS (post-0 h), and after 6 h of reambulation (post-6 h). Post-0 h soleus fibers expressing type I myosin heavy chain (MHC) showed significant reductions in diameter, absolute and specific peak Ca2+-activated force, unloaded shortening velocity, and absolute and normalized peak power. Fibers obtained from the gastrocnemius were less affected by ULLS, particularly fibers expressing fast MHC isoforms. Post-6 h soleus fibers produced less absolute and specific peak force than did post-0 h fibers, suggesting that reambulation after ULLS induced cell damage. Like bed rest and spaceflight, ULLS primarily affects soleus over gastrocnemius fibers. However, in contrast to these other models, slow soleus fibers obtained after ULLS showed a decrease in unloaded shortening velocity and a greater reduction in specific force.     

H-reflex and motor evoked potential changes during head down bed rest

The purpose of the present study was to investigate effect of un-loading lower limb on H-reflex and motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) during bed rest.     

21 Days head-down bed rest induces weakening of cell-mediated immunity - Some spaceflight findings confirmed in a ground-based analog

Several studies indicate a weakening of cell-mediated immunity (CMI) and reactivation of latent herpes viruses during spaceflight. We tested the hypothesis that head-down bed rest (HDBR), a ground-based analog of spaceflight, mimics the impact of microgravity on human immunity. Seven healthy young males underwent two periods of 3 weeks HDBR in the test facility of the German Aerospace Center. As a nutritional countermeasure aimed against bone demineralisation, 90 mmol potassium bicarbonate (KHCO(3)) was administered daily in a crossover design. Blood samples were drawn on five occasions. Whole blood was stimulated with antigen i.e. Candida albicans, purified protein derivative (PPD) tuberculin, tetanus toxoid and Cytomegalovirus (CMV) (CMV-QuantiFERON). Flow cytometric analysis included CD4(+)CD25(+)CD127(-)FOXP3(+) regulatory T cells (Tregs), γδ T cells, B cells, NK cells and dendritic cells. In one of the two bed rest periods, we observed a significant decrease in production of interleukin-2 (IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) following phytohemagglutinin (PHA) stimulation, with a rapid normalization being observed after HDBR. The cytokine levels showed a V-shaped pattern that led to a relativeTh2-shift in cytokine balance. Only three individuals responded to the specific T cell antigens without showing signs of an altered response during HDBR, nor did we observe reactivation of CMV or Epstein-Barr virus (EBV). Of unknown significance, dietary supplementation with KHCO(3) counteracted the decrease in IL-2 levels during HDBR, while there was no impact on other immunological parameters. We conclude that discrete alterations in CMI may be induced by HDBR in selected individuals.     

Strength training counteracts motor performance losses during bed rest.

The purpose of the study was to determine the effect of bed rest with or without strength training on torque fluctuations and activation strategy of the muscles. Twelve young men participated in a 20-day bed rest study. Subjects were divided into a non-training group (BRCon) and a strength-training group (BRTr). The training comprised dynamic calf-raise and leg-press exercises. Before and after bed rest, subjects performed maximal contractions and steady submaximal isometric contractions of the ankle extensor muscles and of the knee extensor muscles (2.5-10% of maximal torque). Maximal torque decreased for both the ankle extensors (9%, P < 0.05) and knee extensors (16%, P < 0.05) in BRCon but not in BRTr. For the ankle extensors, the coefficient of variation (CV) for torque increased in both groups (P < 0.05), with a greater amount (P < 0.05) in BRCon (88%) compared with BRTr (41%). For the knee extensors, an increase in the CV for torque was observed only in BRCon (22%). The increase in the CV for torque in BRCon accompanied the greater changes in electromyogram amplitude of medial gastrocnemius (122%) and vastus lateralis (59%) compared with BRTr (P < 0.05). The results indicate that fluctuations in torque during submaximal contractions of the extensor muscles in the leg increase after bed rest and that strength training counteracted the decline in performance. The response varied across muscle groups. Alterations in muscle activation may lead to an increase in fluctuations in motor output after bed rest.     

Insulin and glucose responses during bed rest with isotonic and isometric exercise

The effects of daily intensive isotonic (68% maximum oxygen uptake (VO2 max)) and isometric (21% maximum extension force) leg exercise on plasma insulin and glucose responses to an oral glucose tolerance test (OGTT) during 14-day bed-rest (BR) periods were investigated in seven young healthy men. The OGTT was given during ambulatory control and on day 10 of the no-exercise, isotonic, and isometric exercise BR periods during the 15-wk study. The subjects were placed on a controlled diet (mean +/- SD = 344 +/- 34 g CHO/day and 3,073 +/- 155 (SD) kcal/day) starting 10 days before each BR period. During BR, basal plasma glucose concentration remained unchanged with no exercise, but increased (P less than 0.05) to 87-89 mg/100 ml with both exercise regimens on day 2, and then fell slightly below control levels on day 13. The fall of glucose content (-11 to -15%) during BR was independent of the exercise regimen and was an adjustment for the loss of plasma vol. The intensity of the response of insulin and glucose to the OGTT (integrated area under the curves) was inversely proportional to the total daily energy expenditure during BR; i.e., the largest response with no exercise, then isometric, isotonic, and ambulatory exercise. It was estimated that at least 1,020 kcal/day must be provided by supplemental exercise to restore the hyperinsulinemia to control levels.     

Resistance exercise maintains skeletal muscle protein synthesis during bed rest

Ferrando, Arny A., Kevin D. Tipton, Marcas M. Bamman, andRobert R. Wolfe. Resistance exercise maintains skeletal muscle protein synthesis during bed rest. J. Appl.Physiol. 82(3): 807-810, 1997.Spaceflightresults in a loss of lean body mass and muscular strength. Aground-based model for microgravity, bed rest, results in a loss oflean body mass due to a decrease in muscle protein synthesis (MPS).Resistance training is suggested as a proposed countermeasure forspaceflight-induced atrophy because it is known to increase both MPSand skeletal muscle strength. We therefore hypothesized that scheduledresistance training throughout bed rest would ameliorate the decreasein MPS. Two groups of healthy volunteers were studied during 14 days ofsimulated microgravity. One group adhered to strict bed rest (BR;n = 5), whereas a second group engagedin leg resistance exercise every other day throughout bed rest (BREx;n = 6). MPS was determined directly bythe incorporation of infusedL-[ring-¹³C₆]phenylalanineinto vastus lateralis protein. After 14 days of bed rest, MPS in theBREx group did not change and was significantly greater than in the BRgroup. Thus moderate-resistance exercise can counteract the decrease inMPS during bed rest.

     

Cardiorespiratory deconditioning with static and dynamic leg exercise during bed rest.

Bed rest deconditioning was assessed in seven healthy men (19-22 yr) following three 14-day periods of controlled activity during recumbency by measuring submaximal and maximal oxygen uptake (VO2), ventilation (VE), heart rate, and plasma volume. Exercise regimens were performed in the supine position and included a) two 30-min periods daily of intermittent static exercise at 21% of maximal leg extension force, and b) two 30-min periods of dynamic bicycle ergometer exercise daily at 68% of VO2max. No prescribed exercise was performed during the third bed rest period. Compared with their respective pre-bed rest control values, VO2max decreased (P less than 0.05) under all exercise conditions; -12.3% with no exercise, -9.2% with dynamic exercise, but only -4.8% with static exercise. Maximal heart rate was increased by 3.3% to 4.9% (P less than 0.05) under the three exercise conditions, while plasma volume decreased (P less than 0.05) -15.1% with no exercise and -10.1% with static, but only -7.8% (NS) with dynamic exercise. Since neither the static nor dynamic exercise training regimes minimized the changes in all the variables studied, some combination of these two types of exercise may be necessary for maximum protection from the effects of the bed deconditioning.