Aerospace Cardiology: Historical foundations, physiological adaptation, and future challenges in human spaceflight

Abstract

Long-duration spaceflight exposes astronauts to unique environmental stressors—primarily microgravity and galactic cosmic radiation (GCR)—that induce profound structural and functional adaptations within the human cardiovascular system. Understanding the pathophysiological mechanisms governing this coordinated deconditioning is critical for ensuring crew safety during future interplanetary exploration profiles. This comprehensive review synthesizes contemporary clinical, histological, molecular, and multi-omic evidence to map the kinetics of spaceflight-induced cardiovascular remodeling and evaluate the efficacy of emerging countermeasure matrices. A systematic synthesis of physiological data from low Earth orbit missions, terrestrial analogues (head-down bed rest), animal models exposed to high-linear energy transfer (high-LET) heavy ions, and advanced multi-omic datasets (including single-cell transcriptomics) was performed. The elimination of hydrostatic pressure gradients drives an immediate cephalad fluid shift, prompting an acute increase in central blood volume followed by a progressive reduction in total circulating plasma volume. Chronically, the myocardium exhibits high plasticity, characterized by left ventricular mass loss and diffuse microstructural remodeling to match decreased volumetric demands. Concurrently, regional vascular beds undergo divergent phenotypic alterations: lower-limb conduit arteries experience low shear stress, inducing inward hypertrophic remodeling, smooth muscle cell phenotypic switching, and matrix degradation, while the upper-body and cerebral vasculature undergoes outward hypertrophy. Multi-omic profiles demonstrate that high-LET HZE particles accelerate atherogenesis via unrepairable DNA double-strand breaks, endothelial cell senescence, and persistent oxidative stress. Furthermore, continuous venous congestion impairs dynamic cerebrovascular autoregulation and compounds altered cerebrospinal fluid redistribution, contributing to Spaceflight-Associated Neuro-ocular Syndrome (SANS). Traditional exercise regimens fail to mitigate these integrated microstructural and molecular updates completely. Preserving cardiovascular and endothelial integrity during deep-space transit demands a transition toward multi-systemic countermeasure paradigms. The integration of short-radius artificial gravity centrifugation with targeted pharmacogenomics—such as microRNA mimics and specific senolytic or anti-inflammatory cascade inhibitors—offers the most viable biophysical and biomolecular framework to safeguard the cellular architecture of human crews during interplanetary travel.