Flow regulation and oxygen transport in microcirculation

描述(由申请人提供)：血流是如何调节的，即血流如何与组织需求相匹配，这是心血管生物学的中心问题。本研究的总体目标是建立骨骼肌微血管网络中氧运输和血流调节的定量理论模型。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一个合理的结构，并可能为控制组织灌流提供新的治疗方法。具体目的是：1.建立预测骨骼肌微血管网血管张力分布的理论模型。我们将建立方程来描述血管张力与代谢因素、管壁切应力、压力和管壁传导反应的关系。这些方程，结合网络血流动力学的方程，将被求解以预测每个节段的音调和内径。将氧运输的理论模型与血流调节模型相结合，描述微血管网络如何调节血流以响应氧气需求的变化。在观察到的网络结构的基础上，将开发静息骨骼肌中氧运输的理论模拟。将开发考虑肌肉纤维组织成运动单位的工作肌肉模型。基于微血管水平的氧运输和血流调节过程，开发全器官需氧量与骨骼肌血流灌注之间关系的理论预测。在目标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、组织氧气水平)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测的详细比较。这将通过研究人员与实验生理学家长期密切的合作而得到促进。

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.