Gender Differences in Response to Simulated Microgravity With and Without Coutermeasure

This KY NASA EPSCoR proposal is being submitted in order to add a young investigator from the University of Kentucky, with unique capabilities in cardiac mechanics, to an existing team of senior, EPSCoR cluster, investigators who have direct research ties to the NASA Ames and Johnson Space Centers. Our on-going collaborative research program with both of these NASA Centers focuses on space flight-induced cardiovascular deconditioning and appropriate countermeasures and is tightly linked to crew safety needs identified by NASA as critical to this country's mission to establishing a moon base and ultimately to the exploration of Mars. From this collaborative research, it is becoming increasing clear that important scientific data related to gender is missing and vitally hampering efforts to develop crew protection for future space exploration. The infusion of relatively inexpensive animal studies in combination with ongoing very expensive and time consuming human studies can be an efficient way to fulfill this gap in information. Hence, we propose the introduction of highly directed animal studies of cardiovascular function to parallel some of our previous and upcoming studies with human subjects. The central hypothesis of this application is that females are more susceptible to orthostatic cardiovascular stress as seen with spaceflight because they exhibit higher levels of diastolic myocardial stiffness. This research uses an animal model to test this hypothesis. Experiments will compare myocardial stiffness in 6 groups of experimental rats: control male and female animals, male and female animals subjected to simulated microgravity via hind-limb unloading (HLU) for 28 days, and male and female animals subjected to HLU with a countermeasure (1hr/day of hind-limb loading, i.e. normal, tethered, standing). A stiffer, less compliant heart after a period of spaceflight in women compared to men could be a factor in the increased orthostatic intolerance upon return to earth or in an upright posture. Upon conclusion of the proposed research, we may be able to propose potential therapeutic strategies offered currently by pharmaceuticals and/or provide additional knowledge that will aid in helping NASA's ongoing process to optimize (per gender differences) the artificial gravity (via centrifuge) countermeasure. Funding of this proposal will significantly enhance our ongoing research program (some of which is funded by EPSCoR and some by NASA Centers directly) and will increase our competitiveness to attract future funding.