Flow regulation and Oxygen transpot in microcirculation

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并在尽管动脉压变化的情况下保持灌注是心血管生物学中的中心问题。拟议的研究的总体目标是建立定量的理论模型，在骨骼肌和其他组织的微血管网络中的血流调节和氧运输。该模型将阐明协调血管阻力变化的机制的作用，将提供一个合理的结构来解释实验数据，并可能导致控制组织灌注的治疗方法的改进。具体目标是：（1）建立理论模型，模拟微血管网络对动脉压变化的自动调节反应，并将预测结果与实验数据进行比较。网络范围从一个代表性的流动途径，以活体显微镜观察到的现实结构将被考虑。将包括生肌性、代谢性、剪切依赖性和传导性反应的影响。预测结果将与骨骼肌和其他组织中血流自动调节的全器官数据进行比较。(2)开发理论模型来模拟微血管网络对代谢需求变化的血流调节，并将预测与实验数据进行比较。将分析红细胞释放ATP在血流调节中的作用。一个初步的模型描述了这种机制在一个单一的部分将扩展到更现实的网络结构。将使用模拟评估沿着血管壁传导响应的相对作用以及小静脉和相关小动脉之间的扩散耦合。血流量和耗氧量之间的预测关系将与骨骼肌中获得的实验数据进行比较。(3)建立预测骨骼肌微血管网血管张力分布的理论模型，并与实验数据进行比较。一个综合的流量调节模型，将所有上述影响和三维网络几何形状的现实信息，将用于预测组织和血管氧水平的分布和骨骼肌微血管网络中的血管张力分布。预测将与实验测量的分布在相同的血管网络进行比较。

DESCRIPTION (provided by applicant): How blood flow is regulated, i.e., how perfusion is matched to tissue demands and maintained despite changes in arterial pressure, is a central question in cardiovascular biology. The overall objective of the proposed studies is to develop quantitative theoretical models for blood flow regulation and oxygen transport in microvascular networks of skeletal muscle and other tissues. 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 lead to improved therapeutic approaches for controlling tissue perfusion. The specific aims are: (1) To develop theoretical models to simulate the autoregulatory response of microvascular networks to changes in arterial pressure, and to compare predictions with experimental data. Networks ranging from a representative flow pathway to realistic structures observed by intravital microscopy will be considered. Effects of myogenic, metabolic, shear-dependent and conducted responses will be included. Predictions will be compared with whole-organ data on flow autoregulation in skeletal muscle and other tissues. (2) To develop theoretical models to simulate the regulation of blood flow by microvascular networks in responses to changes in metabolic demand, and to compare predictions with experimental data. The role of ATP release by red blood cells in flow regulation will be analyzed. A preliminary model describing this mechanism in a single segment will be extended to more realistic network structures. The relative roles of conducted responses along vessel walls and diffusive coupling between venules and associated arterioles will be assessed using simulations. Predicted relationships between blood flow and oxygen consumption will be compared with experimental data obtained in skeletal muscle. (3) To develop theoretical models to predict distributions of vascular tone in microvascular networks of skeletal muscle, and to compare these with experimental data. An integrated model for flow regulation, incorporating all the above effects and realistic information on three-dimensional network geometry, will be used to predict distributions of tissue and vessel oxygen levels and distributions of vascular tone in microvascular networks in skeletal muscle. Predictions will be compared with experimentally measured distributions in the same vascular networks.