BME PhD Defense Announcement for Joseph C. Muskat (V. Rayz and C. Goergen, Co-Chairs) Everyone is invited to attend the public presentation beginning at 2:00PM. Dissertation Title: Application of Multiscale Hemodynamic Models to Explore the Action of Nitrite as a Vasodilator during Acute Cardiovascular Stress Date: November 30th, 2022 Time: 2:00PM Location: MRGN 121 and virtually (https://purdue-edu.zoom.us/j/93964160161?pwd=Ui9Od2hTNU9sek04Y3gwTlZ2clZlZz0...) Advisory Committee: Vitaliy L. Rayz, Co-Chair Craig J. Goergen, Co-Chair Charles F. Babbs Elsje Pienaar Abstract: The fluid dynamics of blood in the systemic circulation modulates production of nitric oxide (NO), a potent vasodilator. Non-invasive techniques such as the flow-mediated dilation (FMD) test and physiologic phenomena associated with autonomic stress induce hyperemia and subsequently higher levels of wall shear stress (WSS), stimulating endothelial nitric oxide synthase (eNOS) expression. In the current clinical practice, WSS-a key regulator of endothelial function-is commonly estimated assuming a parabolic velocity distribution, despite the evidence that the temporal changes of pulsatile blood flow over the cardiac cycle modulates vasodilation in mammals. This work investigates the effect of cardiovascular stress on local WSS distributions and the potential for accumulation of near-wall nitrite, the vasoactive storage form of NO in the bloodstream. The specific aims of the project are therefore as follows: 1) develop a reduced-order model of the major systemic vasculature at rest, during a flight-or-flight response, and under moderate levels of aerobic exercise; 2) derive a velocity-driven Womersley solution for pulsatile flow to support accurate estimation of pulsatile WSS in the clinical setting; and 3) quantify cumulative transport of nitrite in a multiscale model of bifurcating vasculature utilizing computational fluid dynamics (CFD). Development of these open-source, translatable methods enable accurate quantification of hemodynamics and species transport during cardiovascular stress. Results detailed herein extend our knowledge about hemodynamics of vascular homeostasis during autonomic stress, suggest a convergent evolutionary theory for having a complete circle of Willis, and potentially clarify reproducibility concerns associated with the FMD test.