Flow regulation and oxygen transport in microcirculation

微循环中的流量调节和氧气输送

• 批准号: 6877175
• 负责人: Timothy W. Secomb
• 金额: $ 11.36万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-03 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6877175
• 关键词: blood vessels; computer simulation; hemodynamics; mathematical model; metabolism; microcirculation; model design /development; organ; oxygen transport; perfusion; spectrometry; striated muscles; vascular resistance; vasoconstriction

DESCRIPTION (provided by applicant): How blood flow is regulated, i.e., how perfusion is matched to tissue demands, is a central question in cardiovascular biology. The overall objective of the proposed studies is to develop quantitative theoretical models for oxygen transport and blood flow regulation in microvascular networks of skeletal muscle. The models will clarify the roles of mechanisms that coordinate changes in vascular resistance, will provide a rational structure for interpreting experimental data, and may suggest new therapeutic approaches for controlling tissue perfusion. The specific aims are:1. To develop theoretical models to predict distributions of vascular tone in microvascular networks of skeletal muscle. Equations will be developed to describe the dependence of vascular tone on metabolic factors, wall shear stress, pressure and conducted responses in vessel walls. These equations, combined with those of network hemodynamics, will be solved to predict tone and internal diameter of each segment.2. To combine theoretical models for oxygen transport with models for flow regulation, to describe how microvascular networks regulate flow in response to changes in oxygen demand. Theoretical simulations of oxygen transport in resting skeletal muscle will be developed based on observed network structures. Models for working muscle will be developed that take into account the organization of muscle fibers into motor units.3. To develop theoretical predictions of the relationship between whole-organ oxygen demand and perfusion in skeletal muscle, based on microvascular-level oxygen transport and flow regulation processes. Results obtained in aims 1 and 2 will be used to predict variation ofmacroscopic variables (flow, consumption, extraction, tissue oxygen level) with demand.In all these studies, particular emphasis will be placed on detailed comparisons of model predictions with experimental observations. This will be facilitated by the investigator's longstanding and close collaboration with experimental physiologists.

描述（由申请人提供）：如何调节血流，即，灌注如何与组织需求相匹配是心血管生物学中的中心问题。 提出的研究的总体目标是建立定量的理论模型，在骨骼肌微血管网络的氧运输和血流调节。 这些模型将阐明协调血管阻力变化的机制的作用，将为解释实验数据提供合理的结构，并可能提出控制组织灌注的新治疗方法。 具体目标是：1. 建立预测骨骼肌微血管网血管张力分布的理论模型。 将开发方程来描述血管张力对代谢因素、壁切应力、压力和血管壁传导响应的依赖性。 结合网络血流动力学方程，求解这些方程，预测各节段的音调和内径. 结合联合收割机氧运输的理论模型与流量调节模型，描述微血管网络如何调节流量以响应氧需求的变化。 基于观察到的网络结构，将开发静息骨骼肌中氧转运的理论模拟。 工作肌肉的模型将被开发出来，考虑到肌肉纤维组织成运动单位。 基于微血管水平的氧运输和流量调节过程，建立全器官氧需求和骨骼肌灌注之间关系的理论预测。 目标1和目标2中获得的结果将用于预测宏观变量（流量、消耗、提取、组织氧水平）随需求的变化。在所有这些研究中，将特别强调模型预测与实验观察的详细比较。 这将通过研究者与实验生理学家的长期密切合作来促进。