Flow regulation and oxygen transport in microcirculation

微循环中的流量调节和氧气输送

• 批准号: 7886941
• 负责人: Timothy W. Secomb
• 金额: $ 18.63万
• 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 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7886941
• 关键词: Accounting; Area; Arteries; Basic Science; Behavior; Biology; Blood; Blood Vessels; Blood capillaries; Blood flow; Caliber; Cardiovascular Physiology; Cardiovascular system; Cells; Clinical; Collaborations; Coupled; Data; Diffuse; Disease; Erythrocytes; Grant; Heterogeneity; Hypoxia; Individual; Intervention; Ischemia; Lead; Learning; Mechanics; Metabolic; Microcirculation; Modeling; Muscle Tonus; Normal tissue morphology; Oxygen; Perfusion; Pharmaceutical Preparations; Process; Regulation; Role; Skeletal Muscle; Smooth Muscle; Structure; Testing; Theoretical model; Therapeutic; Time; Tissues; Transport Process; Variant; Vascular System; Vasodilation; Work; active control; arteriole; base; capillary; experience; improved; insight; oxygen transport; pressure; public health relevance; response; spatial temporal variation; vasomotion

DESCRIPTION (provided by applicant): Regulation of blood flow is a central topic in cardiovascular biology. Many disorders involve dysfunctional flow regulation, and vasoactive drugs are frequently used in treating these disorders. Delivery of an adequate oxygen supply is the most critical function of the circulatory system. The overall objective of this project is to develop quantitative theoretical models for blood flow regulation and oxygen transport in microvascular networks. In prior studies supported by this grant, we developed a model for steady-state flow regulation in a network with a homogeneous structure. That model, which will form the basis for the proposed studies, has provided insights into the roles of myogenic, metabolic, shear-dependent and conducted responses and oxygen-dependent release of ATP by red blood cells in the regulation of flow. In the proposed work, we will examine the effects of heterogeneity, time-dependent behavior and capillary recruitment on flow regulation. Specific Aim 1 is to develop theoretical models for flow regulation in microvascular networks with inhomogeneous structures and spatially varying metabolic demand. The models will be used to investigate the mechanisms by which perfusion is locally matched to metabolic demand in normal tissue and how this fails in abnormal states. Specific Aim 2 is to develop theoretical models for time- dependent flow regulation in response to changes in metabolic demand and arterial pressure, and to apply this model to analyze spontaneous oscillations in arteriolar diameter and blood flow (arteriolar vasomotion) that occur in some conditions. Specific Aim 3 is to develop theoretical models including effects of capillary recruitment, and to test their ability to describe the more than 25-fold observed dynamic range of skeletal muscle perfusion. In all these studies, emphasis will be placed on comparing model predictions with available experimental data and using these data to further develop, test and refine the models. This process will be facilitated by well established collaborations with two consultants, Dr. Axel Pries and Dr. Tuhin Roy, who have extensive experience in relevant experimental basic science and clinical areas respectively. PUBLIC HEALTH RELEVANCE: 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. The models will clarify the roles of mechanisms that coordinate blood flow with local tissue requirements, will provide a rational structure for interpreting experimental data, and may lead to improved therapeutic approaches for controlling tissue perfusion.

描述(申请人提供)：血流调节是心血管生物学的中心课题。许多疾病涉及功能失调的血流调节，血管活性药物经常用于治疗这些疾病。提供充足的氧气供应是循环系统最关键的功能。该项目的总体目标是开发微血管网络中血流调节和氧气运输的定量理论模型。在这笔拨款支持的先前研究中，我们开发了一个具有均匀结构的网络中的稳态流量调节模型。该模型将成为拟议研究的基础，它为肌源性、代谢性、剪切性和传导性反应以及红细胞对ATP的氧依赖性释放在血流调节中的作用提供了见解。在拟议的工作中，我们将研究异质性、时间依赖行为和毛细管招募对流动调节的影响。具体目标1是为具有不均匀结构和空间变化的代谢需求的微血管网络中的流量调节建立理论模型。这些模型将被用来研究正常组织中局部灌注与代谢需求相匹配的机制，以及在异常状态下这一机制是如何失败的。具体目标2是建立响应代谢需求和动脉压变化的随时间变化的血流调节的理论模型，并应用该模型分析在某些条件下发生的小动脉直径和血流量(小动脉血管运动)的自发振荡。具体目标3是开发包括毛细血管再充盈效应在内的理论模型，并测试它们描述骨骼肌血流灌流动态范围超过25倍的能力。在所有这些研究中，重点将放在将模型预测与现有的实验数据进行比较，并使用这些数据来进一步开发、测试和改进模型。这一进程将通过与阿克塞尔·普里斯博士和图欣·罗伊博士两位顾问的良好合作来推动，这两位顾问分别在相关的实验基础科学和临床领域拥有丰富的经验。 公共卫生相关性：血流如何调节，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，是心血管生物学的中心问题。这项研究的总体目标是建立微血管网络中血流调节和氧气运输的定量理论模型。这些模型将阐明协调血流与局部组织需求的机制的作用，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。