Multiphase Flow Dynamics of Blood Cells in Compliant Vessels: Towards A Computational Study of Autoregulation of Blood Flow in Microcirculation

顺应性血管中血细胞的多相流动力学：微循环中血流自动调节的计算研究

• 批准号: 1922839
• 负责人: Prosenjit Bagchi
• 金额: $ 34.89万
• 依托单位: Rutgers University New Brunswick
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1922839&HistoricalAwards=false
• 关键词: Multiphase; Flow; Dynamics; Blood; Cells

Blood pumped from the heart to various parts of the body is conveyed by a hierarchy of blood vessels. This vascular system supplies oxygen nutrients to cells in the body and removes carbon dioxide and metabolic waste. The terminal blood vessels are capillaries, and this is where gas and nutrient exchange with surrounding tissue takes place. Demand for oxygen and nutrients varies with time in specific tissues. For example, cerebral neurons demand more oxygen during increased cognitive activities. Each organ and tissue is able to regulate its blood supply on demand. Blood flow regulation at the capillary level is known as autoregulation, and it involves dilation and contraction of vessels triggered by smooth muscle cells (SMCs) in the pre-capillary vessel wall. Autoregulation allows the capillaries to maintain constant blood flow rates despite sudden changes in pressure. Loss of autoregulation is associated with many pathological conditions, including dementia and coronary disease. Compliance of blood vessels is the key to the process. Red blood cells (RBCs) are extremely flexible; their motion through capillaries influences overall blood flow and pressure distributions, which in turn affect activation of pressure-sensitive SMCs. This project will develop a computational model of autoregulation of blood flow by combining RBC deformation, SMC activation, and vessel compliance. The model will provide a detailed understanding of the critical pathways that cause loss of autoregulation and its effects in various diseases such as dementia, stroke, heart disease, kidney failure. The project will involve mentoring graduate and undergraduate students in research, and will engage high-school students through a summer research program.This project will develop a high-fidelity, three-dimensional, multiscale, multiphysics, fluid-structure interaction (FSI)-based computational model of autoregulation of blood flow in physiologically realistic vascular networks. It will integrate a coarse-grain bio-electro-chemical model for calcium ion-mediated active contractile stress generation in SMCs, finite-strain viscoelastic model for the dynamic response of the blood vessel walls, large deformation of flowing RBCs in suspension, and Immersed Boundary methods to couple the fluid flow with deforming interfaces. The influence of vessel compliance on RBC deformation and distribution, and the role of RBC rheology on vessel deformation will be analyzed quantitatively. The apparent viscosity of blood in compliant vessels, and the effects of vessel compliance on RBC partitioning at vascular bifurcations will also be addressed. Finally, the role of active contraction on the distribution of RBCs in a vascular network, and the role of RBC distribution on active contraction will be studied.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

血液从心脏泵送到身体的各个部位，是由一系列血管输送的。这个血管系统为体内细胞提供氧气营养，并清除二氧化碳和代谢废物。末端血管是毛细血管，这是与周围组织进行气体和营养交换的地方。特定组织对氧气和营养物质的需求随时间而变化。例如，大脑神经元在认知活动增加时需要更多的氧气。每个器官和组织都能够根据需要调节其血液供应。毛细血管水平的血流调节被称为自动调节，它涉及由前毛细血管壁中的平滑肌细胞（SMC）触发的血管扩张和收缩。 自动调节使毛细血管能够在压力突然变化的情况下保持恒定的血液流速。自动调节的丧失与许多病理状况相关，包括痴呆和冠状动脉疾病。 血管的顺应性是这一过程的关键。 红细胞（RBC）非常灵活;它们通过毛细血管的运动会影响整体血流和压力分布，进而影响压力敏感SMC的激活。本计画将结合红细胞变形、平滑肌细胞活化与血管顺应性，发展一个血流自动调节的计算模型。该模型将详细了解导致自动调节丧失的关键途径及其在各种疾病中的影响，如痴呆症，中风，心脏病，肾衰竭。该项目将包括指导研究生和本科生的研究，并将通过暑期研究计划吸引高中生参与。该项目将开发一个高保真、三维、多尺度、多物理场、基于流体-结构相互作用（FSI）的计算模型，用于在生理上真实的血管网络中进行血流自动调节。它将整合一个粗粒生物电化学模型的钙离子介导的主动收缩应力产生的SMC，有限应变粘弹性模型的血管壁的动态响应，大变形的悬浮液中流动的红细胞，浸没边界方法耦合的流体流动与变形界面。定量分析血管顺应性对红细胞变形和分布的影响，以及红细胞流变性对血管变形的作用。顺应性血管中血液的表观粘度，以及血管顺应性对血管分叉处RBC分配的影响也将得到解决。最后，将研究主动收缩对红细胞在血管网络中分布的作用，以及红细胞分布对主动收缩的作用。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。