RHEOLOGICAL DETERMINANTS OF MICROVASCULAR FUNCTION

这项研究的总体目标是阐明血液的作用 流变学作为健康微血管功能的决定因素， 疾病 为此，活体显微镜技术将被 应用于评估红细胞（RBC） 变形性和聚集性以及白色血细胞（WBC）变形性 以及与内皮的粘附，影响血液流动的阻力， 从真正的毛细血管到小动脉和小静脉 为他们服务。微血管功能的定量指标将 从血流动力学变量的直接原位测量中得出， 外置组织如肠系膜、网膜和提睾肌 肌肉. 具体目标是阐明 血液流动和血液结肠机械性能在个人 微血管，在整个微血管网络的分支点， 区域性地贯穿于主要微血管分裂的连续过程。 这项研究的一个主要重点将是阐明微血管 在低流量状态下， 动脉流入，出血性低血压或药物 干预 对红细胞的具体研究将描述红细胞的作用， 白细胞边缘的细胞聚集，区域耐药性， 血流和从长期缺血发作中恢复。 研究 红细胞变形性将试图阐明其降低的影响 在组织缺氧期间毛细血管募集的过程中， 其对区域流动阻力和阻力的影响 在单个无分支的微血管中流动。 红细胞浓度的研究 将致力于阐明平均组织 红细胞压积，由红细胞通过 微血管和管红细胞压积，通过直接 在单个微血管中进行测量。 白细胞变形能力的作用 将作为WBC粘附于内皮的决定因素进行检查， 流动阻力。光学切片显微镜技术将是 应用于阐明微血管中的不规则性 管腔在影响血流阻力方面发挥作用。 预计 这些研究的结果将提供深入了解的作用， 血细胞的机械和生化特性影响 微血管功能，并帮助制定治疗策略， 治疗各种病理，如贫血，红细胞增多症，低 流动状态、休克、炎症和血细胞紊乱，仅举几例。

The overall goal of this research is to elucidate the role of blood rheology as a determinant of microvascular function in health and disease. To this end, techniques of intravital microscopy will be applied to evaluate the extent to which red blood cell (RBC) deformability and aggregation, and white blood cell (WBC) deformability and adhesion to the endothelium, affect the resistance to blood flow in vessels ranging from the true capillaries, to the arterioles and venules which serve them. Quantitative indices of microvascular function will be derived from direct in situ measurements of hemodynamic variables in exteriorized tissues such as the mesentery, omentum and cremaster muscle. Specific aims are to elucidate the relationship between blood flow and blood coli mechanical properties within individual microvessels, at branch points throughout the microvascular network and regionally throughout the succession of major microvascular divisions. A major emphasis of the research will be to elucidate microvascular function in the low flow state by either mechanical obstruction of the arterial inflow, hemorrhagic hypotension or pharmacological intervention. Specific studies on RBCs will delineate the role of red cell aggregation in the margination of WBCs, regional resistance to blood flow and recovery from prolonged ischemic episodes. Studies on RBC deformability will seek to elucidate the effect of its decrease on the process of capillary recruitment during tissue hypoxia, its effect on regional resistance to flow and on the resistance to flow in single unbranched microvessels. Studies on RBC concentration will aim to elucidate the relationship between average tissue hematocrit, determined by the dynamics of red cell flux through the microvasculature, and the tube hematocrit, obtained by direct measurements in individual microvessels. The role of WBC deformability will be examined as a determinant of WBC adhesion to the endothelium and resistance to flow. Techniques of optical sectioning microscopy will be applied to elucidate the role that irregularities in the microvessel lumen play in affecting the resistance to blood flow. It is anticipated that the results of these studies will provide insight into the role of mechanical and biochemical properties of blood cells in affecting microvascular function and aid development of therapeutic strategies to treat a variety of pathologies such as anemia, polycythemia, the low flow state, shock, inflammation and blood cell disorders, to name a few.