Space physiology IV: mathematical modeling of the cardiovascular system in space exploration.

Mathematical modeling represents an important tool for analyzing cardiovascular function during spaceflight. This review describes how modeling of the cardiovascular system can contribute to space life science research and illustrates this process via modeling efforts to study postflight orthostatic intolerance (POI), a key issue for spaceflight. Examining this application also provides a context for considering broader applications of modeling techniques to the challenges of bioastronautics. POI, which affects a large fraction of astronauts in stand tests upon return to Earth, presents as dizziness, fainting and other symptoms, which can diminish crew performance and cause safety hazards. POI on the Moon or Mars could be more critical. In the field of bioastronautics, POI has been the dominant application of cardiovascular modeling for more than a decade, and a number of mechanisms for POI have been investigated. Modeling approaches include computational models with a range of incorporated factors and hemodynamic sophistication, and also physical models tested in parabolic and orbital flight. Mathematical methods such as parameter sensitivity analysis can help identify key system mechanisms. In the case of POI, this could lead to more effective countermeasures. Validation is a persistent issue in modeling efforts, and key considerations and needs for experimental data to synergistically improve understanding of cardiovascular responses are outlined. Future directions in cardiovascular modeling include subject-specific assessment of system status, as well as research on integrated physiological responses, leading, for instance, to assessment of subject-specific susceptibility to POI or effects of cardiovascular alterations on muscular, vision and cognitive function.