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Microgravity Induced Changes in Aortic Stiffness and its Role in Orthostatic Intolerance.   E.C. Tuday, J.V. Meck, A.A. Shoukas, D.E. Berkowitz ¹Dept. of Biomedical Engineering, ²Dept. of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore MD and ³Human Adaptation and Countermeasures Office, NASA Johnson Space Center, Houston, TX

   Microgravity (µG) induced orthostatic intolerance (OI) in astronauts, a common consequence of manned spaceflight, is characterized by a marked decrease in cardiac output (CO) in response to an orthostatic stress. Since CO is highly dependent on venous return, alterations in the resistance to venous return (RVR) may be important in contributing to OI. The RVR is inversely dependent on arterial compliance (C_A), where aortic compliance (C_a) contributes up to 60% of C_A. We tested the hypothesis that µG induced changes in C_a may represent a protective mechanism against OI. A retrospective analysis on hemodynamic data collected from astronauts after 5-18 day spaceflight missions revealed that orthostatically tolerant (OT) astronauts showed a significant decrease in C_a after spaceflight (1.996±0.09741 ml/mmHg to 1.707±0.08313 ml/mmHg; p=0.0011; N =40) while OI astronauts showed a slight increase in C_a (1.888±0.1269 ml/mmHg to 2.280±0.3868 ml/mmHg; p=0.3607; N=17).  A ground based animal model simulating µG, hindlimb unweighted (HLU) rats, was used to explore this phenomenon.  Two independent assessments of C_a, in vivo pulse wave velocity (PWV) of the thoracic aorta and in vitro pressure-diameter squared relationship (PDSR) measurements of the excised thoracic aorta were determined. PWV showed a significant increase in aortic stiffness compared to control (PWV: 7.227±0.1375 m/s vs. 4.074±0.1879 m/s, p<0.0001, N=6) despite unchanged blood pressures. This increase in arterial stiffness was confirmed by the PDSR analysis (PDSR slopes: 176.5 ± 22.47 mmH2O/mm^2 vs. 113.7 ± 5.409 mmH2O/mm^2, p= 0.0216, N=6). Thus both actual µG in humans and simulated µG in rats induces changes in C_a. The difference in C_a in OT and OI astronaut suggests that the µG induced decrease in C_a is a protective adaptation to spaceflight that reduces the RVR and allows for the maintenance of adequate CO in response to an orthostatic stress.