This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Sustained exposure to microgravity leads to adaptive changes in the cardiovascular and musculoskeletal systems that may impair normal function and result in substantial morbidity. For example cardiovascular deconditioning caused by cardiac atrophy, hypovolemia, or limited reflex responsiveness may lead to orthostatic hypotension and syncope. Disuse atrophy of skeleltal muscle will diminish work capacity and may lead to muscle injury. Bone demineralization increases the risk of kidney stone formation, and may reduce bone strength increasing the risk of fracture. Bone resorption may be particularly severe after long duration space flight with uncertain recovery. Virtually all the changes previously observed in short duration space missions may be exacerbated during long duration missions, such as those required aboard the International Space Station, or a mission to Mars. However despite in depth study, the optimal countermeasure for each system has not yet been defined. More importantly, previous work has focused primarily on one organ system at a time, ignoring the interaction among systems, and preventing the development and practical application of a specific countermeasure for an individual astronaut that might be effective for the heart, muscles and bones. The global objective of this proposal is to test an integrated countermeasure that will be effective against cardiovcascular deconditioning, skeletal muscle atrophy, and bone demineralizqtion, and that ultimately can be applied practically aboard the International Space Station or a mission to Mars.
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