Nitric Oxide (NO) Transport Mechanisms: An Engineering Approach

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0301446JaronNitric oxide (NO) plays an important role in regulation of blood flow and metabolism, however, its transport properties and mechanisms of action in the microcirculation are not well understood. The general goal of the proposed research is to use an integrated engineering approach combining mathematical modeling and in vitro and in vivo experiments to improve our understanding of the interacting mechanisms between NO, oxygen, carbon dioxide, hemoglobin, calcium, oxygen free radicals, and thiols in blood and tissue. A comprehensive state-of-the-art computational model coupled with appropriate experiments will be used to evaluate and quantify hypothesized mechanisms of NO transport, evaluate interactions between mechanisms, and to assess the relative contributions of each. The mathematical model will utilize dynamic mass transport and fluid mechanics calculations in conjunction with multiple chemical reactions to simulate production, transport, scavenging, feedback regulation, and other mechanisms of action of NO and associated chemical species in the microcirculation and tissue. Experimental studies have been designed to provide key parameters for mathematical modeling and will be used to test model validity. Quantitative data obtained from the validated model will be used to predict parameters that cannot be measured in vivo, analyze the hypotheses and further the understanding of NO production and transport mechanisms, and shape future studies.