This study was designed to test the hypothesis that 60 days continuous head down bed rest (HDBR), an Earth-based analogue of the effects of space flight, would elevate factors that increase vasoconstriction and would increase markers of vascular inflammation. The study incorporated countermeasures consisting of treadmill running within lower-body negative pressure and resistive "flywheel" exercise (exercise countermeasure, EX) or an increased protein intake of 0. 6 g/kg body weight/day (dietary countermeasures, DIET) to determine whether these interventions might prevent the vasoconstrictor and inflammatory responses when compared to a control (CON) group. Markers of vascular health measured in the study include the vasoactive molecules angiotensin II (Ang II), endothelin-1 (ET-1), and nitric oxide metabolites (NO_met); and markers of inflammation including C-reactive protein (CRP), and the adhesion molecules E-selectin (E-sel), intracellular adhesion molecule-1 (ICAM), and vascular cell adhesion molecule-1 (VCAM). Twenty four women were housed at the MEDES clinic in Toulouse, France, as part of a large international study (Women International Space Simulation for Exploration, WISE) in which various experimental protocols and countermeasures were integrated into a single experimental design completed during two campaigns. Each 100 day campaign included 20 days of pre-testing (pre-HDBR), 60 days of bed rest (HDBR), and 20 days of post-testing (post-HDBR). The experimental countermeasures were applied only during the 60-day HDBR period. Following 60 days of HDBR, many changes occurred in the concentrations of the measured molecules. Specifically, the concentration of Ang II significantly increased in the CON and DIET groups (52. 9%, p = 0. 014; and 124. 4%, p <0. 0001 respectively), but not in the EX group. Also, NO_met decreased in all groups, with reductions in the EX and DIET groups (p = 0. 013, and p = 0. 056 respectively). Markers used to assess vascular inflammation increased following the HDBR. The increase in CRP in the CON and DIET groups and the decrease in the EX group from pre- to post-HDBR were not significant; however, the directional changes resulted in an interaction between group and HDBR (p = 0. 052). The adhesion molecule E-sel was significantly increased in the DIET group (p = 0. 003), and VCAM was significantly increased in the CON group (p = 0. 016) with a smaller increase in the DIET group (p = 0. 08). No changes in adhesion molecules were observed in the EX group. This study demonstrated that 60 days of HDBR by young, healthy, women caused changes in several different molecules that are beginning to emerge as risk factors for the development of cardiovascular diseases. Further, it was observed that regular, vigorous exercise during HDBR prevented these changes. These results suggest that future studies of this kind should directly monitor the effects of simulated space flight on vascular health in men and women to obtain a greater understanding of the adaptations that might occur during long term space exploration missions. HDBR can be considered an extreme model of physical inactivity and could be used to provide insight into mechanisms of disease processes associated with the sedentary lifestyle that is prevalent in Western society.

This study was designed to test the hypothesis that 60 days continuous head down bed rest (HDBR), an Earth-based analogue of the effects of space flight, would elevate factors that increase vasoconstriction and would increase markers of vascular inflammation. The study incorporated countermeasures consisting of treadmill running within lower-body negative pressure and resistive "flywheel" exercise (exercise countermeasure, EX) or an increased protein intake of 0. 6 g/kg body weight/day (dietary countermeasures, DIET) to determine whether these interventions might prevent the vasoconstrictor and inflammatory responses when compared to a control (CON) group. Markers of vascular health measured in the study include the vasoactive molecules angiotensin II (Ang II), endothelin-1 (ET-1), and nitric oxide metabolites (NO_met); and markers of inflammation including C-reactive protein (CRP), and the adhesion molecules E-selectin (E-sel), intracellular adhesion molecule-1 (ICAM), and vascular cell adhesion molecule-1 (VCAM). Twenty four women were housed at the MEDES clinic in Toulouse, France, as part of a large international study (Women International Space Simulation for Exploration, WISE) in which various experimental protocols and countermeasures were integrated into a single experimental design completed during two campaigns. Each 100 day campaign included 20 days of pre-testing (pre-HDBR), 60 days of bed rest (HDBR), and 20 days of post-testing (post-HDBR). The experimental countermeasures were applied only during the 60-day HDBR period. Following 60 days of HDBR, many changes occurred in the concentrations of the measured molecules. Specifically, the concentration of Ang II significantly increased in the CON and DIET groups (52. 9%, p = 0. 014; and 124. 4%, p <0. 0001 respectively), but not in the EX group. Also, NO_met decreased in all groups, with reductions in the EX and DIET groups (p = 0. 013, and p = 0. 056 respectively). Markers used to assess vascular inflammation increased following the HDBR. The increase in CRP in the CON and DIET groups and the decrease in the EX group from pre- to post-HDBR were not significant; however, the directional changes resulted in an interaction between group and HDBR (p = 0. 052). The adhesion molecule E-sel was significantly increased in the DIET group (p = 0. 003), and VCAM was significantly increased in the CON group (p = 0. 016) with a smaller increase in the DIET group (p = 0. 08). No changes in adhesion molecules were observed in the EX group. This study demonstrated that 60 days of HDBR by young, healthy, women caused changes in several different molecules that are beginning to emerge as risk factors for the development of cardiovascular diseases. Further, it was observed that regular, vigorous exercise during HDBR prevented these changes. These results suggest that future studies of this kind should directly monitor the effects of simulated space flight on vascular health in men and women to obtain a greater understanding of the adaptations that might occur during long term space exploration missions. HDBR can be considered an extreme model of physical inactivity and could be used to provide insight into mechanisms of disease processes associated with the sedentary lifestyle that is prevalent in Western society.

Ce travail de thèse a pour but l’étude des douleurs de dos qui surviennent chez l’astronaute présentant davantage de hernies discales par rapport à une population contrôle. Nos recherches visent à comprendre la physiopathologie de ce phénomène et à étudier les conséquences cliniques de ce déconditionnement vertébral qui participe également aux troubles posturaux. Cet axe de recherche est recommandé par les différentes agences spatiales internationales. Pour cela nous avons eu l’opportunité d’analyser les données dans deux modèles d’études des effets de la microgravité : l’immersion sèche (n=11) et l’alitement tête déclive (n=9) et un état analogue, le confinement (n=4). Seuls les principaux résultats de l’immersion sèche, méthode d’étude nouvelle de notre paradigme, sont rapportés dans ce résumé. Celle-ci a permis grâce à l’imagerie et la spectroscopie par résonnance magnétique nucléaire de la colonne vertébrale, d’analyser en 3 dimensions le disque intervertébral et d’objectiver l’augmentation du contenu en eau (+17%) du volume de ce disque (+9,5%). Les variations du tonus des muscles paravertébraux et des membres inférieurs ont été mesurées avec la très récente et non-invasive technologie MyotonPRO. Une diminution du tonus musculaire (-7,3%) a été retrouvée, associée à une atrophie musculaire (-10,6%) ainsi qu’une perte de force démontrée sur les membres inférieurs. Ces résultats, attestant un déconditionnement musculaire, sont cohérents avec le déconditionnement postural immédiatement après immersion sèche. Nous avons également étudié les paramètres d’occlusion dentaire, qui font partie des entrées posturales et peuvent affecter la bonne stabilité du corps. Finalement deux éléments interviennent dans l’explication des dysfonctions vertébrales : l’augmentation de la taille de la colonne liée à celle du volume des disques intervertébraux. On note également une atrophie des muscles paravertébraux, qui joue un rôle majeur dans la posture. Nous avons par ailleurs montré le rôle de l’occlusion dentaire dans le déconditionnement vertébral et postural. En conclusion : le tonus musculaire, la bonne mobilité vertébrale et l’équilibre de l’occlusion dentaire sont des éléments à préserver pendant et après un séjour en impesanteur, afin d’éviter les effets délétères du déconditionnement. / This work focuses on the study of back pain experienced by astronauts, who present with a greater incidence of herniated discs compared to a control population. Our research aims at understanding the physiopathology of this phenomenon and to study the clinical consequences of vertebral deconditioning which also contributes to postural disorders. This line of research has been recommended by the various international space agencies. For this reason, we had the opportunity to analyze data in two models simulating the effects of microgravity: dry immersion (n = 11) and head-down bed rest (n = 9), and a similar state, confinement (n = 4). Only the main results of dry immersion, a new method of studying our paradigm, are reported in this summary. Using magnetic resonance imaging and spectroscopy of the vertebral column, it was possible to analyze the intervertebral disc in 3 dimensions and to objectify the increase in water content (+ 17%) and the increase in intervertebral disc volume (+ 9.5%). Variations in paravertebral and lower limb muscle tone were measured with the very recent, and non-invasive, MyotonPRO technology. A decrease in muscle tone (-7.3%) was found to be associated with muscular atrophy (-10.6%) as well as a loss of strength in the lower limbs. These results, attesting to muscle deconditioning, are consistent with postural impairment immediately after dry immersion. We also studied variations in dental occlusion, which is involved with the maintenance of posture and could affect balance. In summary, two elements are involved in the explanation of vertebral dysfunction: the increase in spine height, related to increased intervertebral discs volume and paravertebral muscles atrophy, which plays a major role in posture. However, we also showed a role of dental occlusion in vertebral and postural deconditioning. In conclusion: muscle tone, good vertebral mobility, and dental occlusion are elements to be preserve during and after an exposure to weightlessness to avoid the deleterious effects of deconditioning.