Flow regulation and Oxygen transpot 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，并在动脉压变化的情况下保持不变，这是心血管生物学的中心问题。这项研究的总体目标是为骨骼肌和其他组织的微血管网络中的血流调节和氧气运输建立定量的理论模型。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，并可能导致改进控制组织灌流的治疗方法。具体目的是：(1)开发理论模型来模拟微血管网络对动脉压变化的自动调节反应，并将预测与实验数据进行比较。将考虑从典型的流动路径到活体显微镜观察到的真实结构的网络。肌源性、代谢性、剪切性和传导反应的影响将被包括在内。预测将与整个器官在骨骼肌和其他组织中的流动自动调节数据进行比较。(2)建立理论模型，模拟微血管网络对代谢需求变化的调节作用，并将预测结果与实验数据进行比较。分析红细胞释放三磷酸腺苷在血流调节中的作用。在单个网段中描述这一机制的初步模型将扩展到更现实的网络结构。将通过模拟评估沿血管壁的传导反应以及小静脉和相关小动脉之间的弥散耦合的相对作用。血流量和耗氧量之间的预测关系将与在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。一个综合了上述效应和三维网络几何信息的流动调节模型将被用来预测骨骼肌微血管网络中组织和血管氧水平的分布和血管张力的分布。预测将与实验测量的相同血管网络中的分布进行比较。

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.