Skeletal Muscle Myofibrillar and Sarcoplasmic Protein Synthesis Rates Are Affected Differently by Altitude-Induced Hypoxia in Native Lowlanders

As a consequence to hypobaric hypoxic exposure skeletal muscle atrophy is often reported. The underlying mechanism has been suggested to involve a decrease in protein synthesis in order to conserve O2. With the aim to challenge this hypothesis, we applied a primed, constant infusion of 1-13C-leucine in nine healthy male subjects at sea level and subsequently at high-altitude (4559 m) after 7–9 days of acclimatization. Physical activity levels and food and energy intake were controlled prior to the two experimental conditions with the aim to standardize these confounding factors. Blood samples and expired breath samples were collected hourly during the 4 hour trial and vastus lateralis muscle biopsies obtained at 1 and 4 hours after tracer priming in the overnight fasted state. Myofibrillar protein synthesis rate was doubled; 0.041±0.018 at sea-level to 0.080±0.018%⋅hr−1 (p<0.05) when acclimatized to high altitude. The sarcoplasmic protein synthesis rate was in contrast unaffected by altitude exposure; 0.052±0.019 at sea-level to 0.059±0.010%⋅hr−1 (p>0.05). Trends to increments in whole body protein kinetics were seen: Degradation rate elevated from 2.51±0.21 at sea level to 2.73±0.13 µmol⋅kg−1⋅min−1 (p = 0.05) at high altitude and synthesis rate similar; 2.24±0.20 at sea level and 2.43±0.13 µmol⋅kg−1⋅min−1 (p>0.05) at altitude. We conclude that whole body amino acid flux is increased due to an elevated protein turnover rate. Resting skeletal muscle myocontractile protein synthesis rate was concomitantly elevated by high-altitude induced hypoxia, whereas the sarcoplasmic protein synthesis rate was unaffected by hypoxia. These changed responses may lead to divergent adaptation over the course of prolonged exposure

Adaptation of Mouse Skeletal Muscle to Long-Term Microgravity in the MDS Mission

The effect of microgravity on skeletal muscles has so far been examined in rat and mice only after short-term (5–20 day) spaceflights. The mice drawer system (MDS) program, sponsored by Italian Space Agency, for the first time aimed to investigate the consequences of long-term (91 days) exposure to microgravity in mice within the International Space Station. Muscle atrophy was present indistinctly in all fiber types of the slow-twitch soleus muscle, but was only slightly greater than that observed after 20 days of spaceflight. Myosin heavy chain analysis indicated a concomitant slow-to-fast transition of soleus. In addition, spaceflight induced translocation of sarcolemmal nitric oxide synthase-1 (NOS1) into the cytosol in soleus but not in the fast-twitch extensor digitorum longus (EDL) muscle. Most of the sarcolemmal ion channel subunits were up-regulated, more in soleus than EDL, whereas Ca2+-activated K+ channels were down-regulated, consistent with the phenotype transition. Gene expression of the atrophy-related ubiquitin-ligases was up-regulated in both spaceflown soleus and EDL muscles, whereas autophagy genes were in the control range. Muscle-specific IGF-1 and interleukin-6 were down-regulated in soleus but up-regulated in EDL. Also, various stress-related genes were up-regulated in spaceflown EDL, not in soleus. Altogether, these results suggest that EDL muscle may resist to microgravity-induced atrophy by activating compensatory and protective pathways. Our study shows the extended sensitivity of antigravity soleus muscle after prolonged exposition to microgravity, suggests possible mechanisms accounting for the resistance of EDL, and individuates some molecular targets for the development of countermeasures

Characteristics of fast voluntary and electrically evoked isometric knee extensions during 56 days of bed rest with and without exercise countermeasure

The contractile characteristics of fast voluntary and electrically evoked unilateral isometric knee extensions were followed in 16 healthy men during 56 days of horizontal bed rest and assessed at bed rest days 4, 7, 10, 17, 24, 38 and 56. Subjects were randomized to either an inactive control group (Ctrl, n = 8) or a resistive vibration exercise countermeasure group (RVE, n = 8). No changes were observed in neural activation, indicated by the amplitude of the surface electromyogram, or the initial rate of voluntary torque development in either group during bed rest. In contrast, for Ctrl, the force oscillation amplitude at 10 Hz stimulation increased by 48% (P < 0.01), the time to reach peak torque at 300 Hz stimulation decreased by 7% (P < 0.01), and the half relaxation time at 150 Hz stimulation tended to be slightly reduced by 3% (P = 0.056) after 56 days of bed rest. No changes were observed for RVE. Torque production at 10 Hz stimulation relative to maximal (150 Hz) stimulation was increased after bed rest for both Ctrl (15%; P < 0.05) and RVE (41%; P < 0.05). In conclusion, bed rest without exercise countermeasure resulted in intrinsic speed properties of a faster knee extensor group, which may have partly contributed to the preserved ability to perform fast voluntary contractions. The changes in intrinsic contractile properties were prevented by resistive vibration exercise, and voluntary motor performance remained unaltered for RVE subjects as well

Calcul des paramètres de l'équation de Wilson. Analyse comparative des représentations d'équilibres liquide-vapeur isothermes par les modèles de Wilson et NRTL Computing Parameters in the Wilson Equation. Comparatrice Analysis of Representations of Isothermal Liquid-Vapor Equilibria by Wilson and Nrtl Models

Un programme de calcul des paramètres de l'équation de Wilson est mis au point. II utilise une méthode itérative de minimisation des écarts sur la pression et la composition de vapeur ou sur chaque grandeur prise séparément. Les méthodes utilisées sont testées sur neuf équilibres liquide-vapeur isothermes de mélanges binaires à déviations positives ou négatives. Les écarts moyens entre les valeurs expérimentales : - de la pression; - de la composition de la vapeur; - de l'enthalpie libre d'excès; et les valeurs calculées à partir des paramètres de Wilson sont comparés à ceux obtenus d'après le modèle NRTL. <br> A program has been developed for computing the parameters in the Wilson equation. It uses an iterative method of minimizing the differences in pressure and steam composition or in each magnitude token separately. The methods used are tried out on nine isothermal liquid-vapor equilibria of binary mixtures with positive or negative deviations. The mean differences between experimental values of the : - pressure; - vapor composition; - excess free enthalpy; and values computed from Wilson parameters are compared with those obtained from an NRTL model

Calcul des paramètres de l'équation de Wilson. Analyse comparative des représentations d'équilibres liquide-vapeur isothermes par les modèles de Wilson et NRTL

Un programme de calcul des paramètres de l'équation de Wilson est mis au point. II utilise une méthode itérative de minimisation des écarts sur la pression et la composition de vapeur ou sur chaque grandeur prise séparément. Les méthodes utilisées sont testées sur neuf équilibres liquide-vapeur isothermes de mélanges binaires à déviations positives ou négatives. Les écarts moyens entre les valeurs expérimentales : - de la pression; - de la composition de la vapeur; - de l'enthalpie libre d'excès; et les valeurs calculées à partir des paramètres de Wilson sont comparés à ceux obtenus d'après le modèle NRTL

Muscle tissue adaptations of high-altitude natives to training in chronic hypoxia or acute normoxia

Twenty healthy high-altitude natives, residents of La Paz, Bolivia (3,600 m), participated in 6 wk of endurance exercise training on bicycle ergometers, 5 times/wk, 30 min/session, as previously described in normoxia- trained sea-level natives (H. Hoppeler, H. Howald, K. E. Conley, S. L. Lindstedt, H. Claassen, P. Vock, and E. R. Weibel. J. Appl. Physiol. 59: 320- 327, 1985). A first group of 10 subjects was trained in chronic hypoxia (HT; barometric pressure = 500 mmHg; inspired O2 fraction = 0.209); a second group of 10 subjects was trained in acute normoxia (NT; barometric pressure 500 mmHg; inspired O2 fraction = 0.314). The workloads were adjusted to ~70% of peak O2 consumption (V̇O2(peak)) measured either in hypoxia for the HT group or in normoxia for the NT group. (V̇O(2peak)) determination and biopsies of the vastus lateralis muscle were taken before and after the training program. (V̇O(2peak)) in the HT group was increased (14%) in a way similar to that in NT sea-level natives with the same protocol. Moreover, (V̇O(2peak)) in the NT group was not further increased by additional O2 delivery during the training session. HT or NT induced similar increases in muscle capillary-to-fiber ratio (26%) and capillary density (19%) as well as in the volume density of total mitochondria and citrate synthase activity (45%). It is concluded that high-altitude natives have a reduced capillarity and muscle tissue oxidative capacity; however, their training response is similar to that of sea-level residents, independent of whether training is carried out in hypobaric hypoxia or hypobaric normoxia

Muscle tissue adaptations of high-altitude natives to training in chronic hypoxia or acute normoxia

Twenty healthy high-altitude natives, residents of La Paz, Bolivia (3,600 m), participated in 6 wk of endurance exercise training on bicycle ergometers, 5 times/wk, 30 min/session, as previously described in normoxia- trained sea-level natives (H. Hoppeler, H. Howald, K. E. Conley, S. L. Lindstedt, H. Claassen, P. Vock, and E. R. Weibel. J. Appl. Physiol. 59: 320- 327, 1985). A first group of 10 subjects was trained in chronic hypoxia (HT; barometric pressure = 500 mmHg; inspired O2 fraction = 0.209); a second group of 10 subjects was trained in acute normoxia (NT; barometric pressure 500 mmHg; inspired O2 fraction = 0.314). The workloads were adjusted to ~70% of peak O2 consumption (V̇O2(peak)) measured either in hypoxia for the HT group or in normoxia for the NT group. (V̇O(2peak)) determination and biopsies of the vastus lateralis muscle were taken before and after the training program. (V̇O(2peak)) in the HT group was increased (14%) in a way similar to that in NT sea-level natives with the same protocol. Moreover, (V̇O(2peak)) in the NT group was not further increased by additional O2 delivery during the training session. HT or NT induced similar increases in muscle capillary-to-fiber ratio (26%) and capillary density (19%) as well as in the volume density of total mitochondria and citrate synthase activity (45%). It is concluded that high-altitude natives have a reduced capillarity and muscle tissue oxidative capacity; however, their training response is similar to that of sea-level residents, independent of whether training is carried out in hypobaric hypoxia or hypobaric normoxia