Nitric Oxide (NO) Transport Mechanisms: An Engineering Approach

一氧化氮（NO）在血液流动和代谢中起着重要的调节作用，但其在微循环中的转运特性和作用机制尚不清楚。本研究的总体目标是采用综合工程方法，将数学建模与体外和体内实验相结合，以提高我们对血液和组织中NO、氧、二氧化碳、血红蛋白、钙、氧自由基和硫醇之间相互作用机制的理解。一个综合的最先进的计算模型与适当的实验相结合，将用于评估和量化NO运输的假设机制，评估机制之间的相互作用，并评估每种机制的相对贡献。该数学模型将利用动态质量传递和流体力学计算，结合多种化学反应来模拟NO及其相关化学物质在微循环和组织中的产生、运输、清除、反馈调节和其他作用机制。实验研究旨在为数学建模提供关键参数，并将用于测试模型的有效性。从验证模型中获得的定量数据将用于预测无法在体内测量的参数，分析假设并进一步了解NO的产生和运输机制，并为未来的研究奠定基础。

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.