Blood flow and structural adaptation in microcirculation

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、动情周期、缺血后侧支循环形成、伤口愈合和肿瘤生长，以及组织工程。在发育初期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，而氧气是最关键的代谢物运输。组织的氧气输送取决于血管网络结构和红血球流量的分布，而红血球的机械行为影响着红血球流量的分布。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满足组织氧气需求的血管结构和血流？理论模型将用于分析结构适应和血液流动所涉及的相互作用的生物过程和物理现象。这些模型将以顾问公司的实验数据为基础，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。这些模型将使用基于分段的方法来描述血管网络结构，并结合氧气和生长因子扩散的连续场描述。该模型将(A)应用于全三维问题，包括肌肉中的网络；(B)扩展到包括分裂和萌芽血管生成(肠套叠)。假设：(I)随机血管生成、结构适应和修剪的过程可以生成结合层次树状结构的网络，以实现长距离有效的对流传输，并生成密集的空间填充网格，以短距离扩散到组织中的每一点。(2)当血管生成刺激和直径增大刺激一致时，发生血管分裂。具体目标2是建立微血管和分叉处血液流动的理论模型，包括内皮表面层的影响。一种计算效率高的方法将被用来模拟多个相互作用的红细胞的运动和变形。该模型将被用来(A)检查红细胞与壁之间的相互作用对它们离开壁的影响，包括内皮细胞表层糖基化的影响；(B)检查多个相互作用的运动 微血管分叉中的细胞，包括内皮表层的影响。假设：(I)无细胞层的宽度由红细胞之间相互作用以及与内皮细胞表面层相互作用的综合影响决定，并可通过包含这些影响的模型进行预测。(Ii)根据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中的分配。

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.