Human Physiology in Deep Space: Cardiovascular and Metabolic Adaptation to Long-Duration Spaceflight

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Long-duration human spaceflight exposes the organism to an environment characterized by microgravity, altered mechanical loading, cephalad fluid redistribution, radiation exposure, confinement, and other factors capable of modifying physiological homeostasis. This review aimed to analyze and integrate current evidence concerning cardiovascular, metabolic, and systemic adaptations associated with prolonged space missions, emphasizing their mechanisms, recovery patterns, and relevance to future human exploration. A structured narrative review based on the scientific method was conducted using international peer-reviewed literature, with priority given to studies indexed in PubMed/MEDLINE and Scopus and to evidence derived from human spaceflight, longitudinal observations, clinically relevant reports, and complementary physiological investigations. The reviewed evidence identified cardiovascular and hemodynamic responses as the predominant research domain, particularly fluid redistribution, plasma-volume regulation, cardiac and vascular remodeling, altered venous circulation, blood-pressure regulation, and postflight orthostatic intolerance. Metabolic and musculoskeletal findings included mechanical unloading, changes in bone remodeling and mineral regulation, physical deconditioning, and alterations that may persist after return to gravity. Renal, immune, molecular, neurovascular, and neuro-ocular responses further demonstrated the multisystem nature of human adaptation to prolonged spaceflight. Recovery was heterogeneous among physiological domains: fluid-volume regulation tended to readjust comparatively rapidly, whereas cardiovascular function, cardiac structure, and immune or molecular responses showed variable trajectories, and some skeletal and neuro-ocular alterations demonstrated slower or incomplete recovery. These findings indicate that long-duration spaceflight should be understood as an integrated physiological challenge requiring longitudinal and individualized monitoring. Future lunar, Martian, and deep-space missions will require combined cardiovascular, metabolic, musculoskeletal, and systemic countermeasures, together with autonomous medical assessment and broader international collaboration to preserve physiological reserve and operational capacity during sustained human exploration beyond Earth.