Blood flow and structural adaptation in microcirculation

微循环中的血流和结构适应

• 批准号: 8645670
• 负责人: Timothy W. Secomb
• 金额: $ 18.22万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8645670
• 关键词: Address; Automobile Driving; Behavior; Biological Process; Blood Vessels; Blood Viscosity; Blood flow; Caliber; Cardiac; Cardiovascular system; Cell Communication; Cell Wall; Cells; Complex; Data; Development; Diffusion; Disease; Erythrocytes; Estrus; Exercise; Funding; Glycocalyx; Growth; Growth Factor; Growth and Development function; Hematocrit procedure; Intussusception; Ischemia; Lead; Length; Methods; Microcirculation; Modeling; Motion; Muscle; Oxygen; Pathologic Processes; Peripheral; Physiological Processes; Process; Property; Simulate; Skeletal Muscle; Stimulus; Stochastic Processes; Structure; Surface; System; Testing; Theoretical model; Thick; Tissue Engineering; Tissues; Trees; Width; Work; Wound Healing; angiogenesis; base; mechanical behavior; meetings; migration; oxygen transport; pressure; simulation; tissue oxygenation; tumor growth; vessel regression

DESCRIPTION (provided by applicant): The microcirculation is a dynamic structure. Networks of microvessels are generated and modified during many physiological and pathological processes, including development, growth, exercise, estrus cycle, collateral formation following ischemia, wound healing and tumor growth, and in tissue engineering. The main processes determining vascular structure after initial development are angiogenesis and structural adaptation. The primary function of the circulatory system is mass transport, and oxygen is the most critical metabolite transported. Oxygen delivery to tissue depends on the vascular network structure and on the distribution of red blood cell flux, which is influenced by the mechanical behavior of red blood cells. This project addresses the following question: How do the processes of angiogenesis and structural adaptation generate vascular structures and blood flows that meet the oxygen needs of the tissue? Theoretical models will be used to analyze the interacting biological processes and physical phenomena involved in structural adaptation and blood flow. The models will be based on and tested using experimental data from the Consultants. Specific Aim 1 is to develop theoretical models for the growth and regression of microvascular networks. The models will use a segment-based approach to describe vascular network structure, combined with a continuous field description of oxygen and growth factor diffusion. The model will be (a) applied to fully three-dimensional problems, including networks in muscle; (b) extended to include splitting as well as sprouting angiogenesis (intussusceptions). Hypotheses: (i) The processes of stochastic angiogenesis, structural adaptation and pruning can generate networks that combine hierarchical tree-like structures for efficient convective transport over large distances, dense space-filling meshes for short diffusion distances to every point in the tissue. (ii) Splitting angiogenesis occurs when stimuli for angiogenesis and for diameter increase coincide. Specific Aim 2 is to develop theoretical models for blood flow in microvessels and bifurcations, including effects of the endothelial surface layer. A computationally efficient method will be used for simulating the motion and deformation of multiple interacting red blood cells. The model will be used (a) to examine the effects of interactions between red blood cells and walls on their migration away from the wall, including effects of endothelial surface layer glycocalyx); (b) to examine the motion of multiple interacting cells in diverging microvessel bifurcations, including effects of endothelial surface layer. Hypotheses: (i) The width of the cell-free layer is determined by the combined effects of red blood cell interactions with each other and with the endothelial surface layer, and can be predicted by a model including these effects. (ii) The partition of hematocrit in diverging bifurcations can be predicted based on the upstream distribution of cells and the effects of cell-cell interactions.

描述（申请人提供）：微循环是一种动态结构。微血管网络在许多生理和病理过程中产生和修饰，包括发育、生长、运动、发情周期、缺血后的侧支形成、伤口愈合和肿瘤生长，以及在组织工程中。在最初发育之后，决定血管结构的主要过程是血管生成和结构适应。循环系统的主要功能是物质运输，氧气是运输的最关键的代谢物。氧气输送到组织取决于血管网络结构和红细胞流量的分布，红细胞流量的分布受红细胞机械行为的影响。这个项目解决了以下问题：血管生成和结构适应的过程如何产生血管结构和血流，以满足组织的氧气需求？理论模型将用于分析结构适应和血液流动中涉及的相互作用的生物过程和物理现象。这些模型将以顾问提供的实验数据为基础，并使用这些数据进行测试。具体目标1是建立微血管网络生长和退化的理论模型。该模型将使用基于段的方法来描述血管网络结构，结合氧气和生长因子扩散的连续场描述。该模型将（a）应用于完全三维的问题，包括肌肉中的网络;（B）扩展到包括分裂以及萌芽血管生成（intusspiration）。假设条件：（i）随机血管生成、结构适应和修剪的过程可以生成网络，该网络将联合收割机分层树状结构与密集空间填充网格相结合，所述分层树状结构用于大距离上的有效对流传输，所述密集空间填充网格用于到组织中的每个点的短扩散距离。(ii)当血管生成和直径增加的刺激一致时，发生分裂血管生成。具体目标2是开发微血管和分叉中血流的理论模型，包括内皮表面层的影响。一种计算效率高的方法将用于模拟多个相互作用的红细胞的运动和变形。该模型将用于（a）检查红细胞和壁之间的相互作用对它们远离壁的迁移的影响，包括内皮表面层糖萼的影响;（B）检查多个相互作用的细胞的运动。 分叉微血管分叉中的细胞，包括内皮表面层的影响。假设条件：（i）无细胞层的宽度由红细胞彼此相互作用以及与内皮表面层相互作用的组合效应决定，并且可以通过包括这些效应的模型来预测。(ii)基于细胞的上游分布和细胞-细胞相互作用的影响，可以预测红细胞压积在分叉分支中的分配。