RHEOLOGICAL DETERMINANTS OF MICROVASCULAR FUNCTION

这项研究计划的总体目标是阐明 血液流变学作为健康和健康人群微血管功能的决定因素 疾病。为此，活体显微镜技术将被 用于评价红细胞(RBC)的变化程度 变形性和聚集性以及白细胞(WBC)变形性 和内皮细胞的黏附，影响血流阻力 血管范围从真正的毛细血管，到小动脉和小静脉 为他们服务。微血管功能的量化指标将是 从直接原位测量血流动力学变量得出 外部化的组织，如肠系膜、大网膜和提睾肌。 其具体目的是阐明血液流动和 单个微血管内的血细胞机械特性，在 贯穿微血管网络和区域的分支点 贯穿于主要微血管分裂的连续过程中。一位少校 这项研究的重点将是阐明糖尿病患者的微血管功能。 由机械干预引起的低流量状态 动脉流入或出血性低血压。关于红细胞的具体研究 将在低流量状态下检查红细胞的隔离和捕获， 对通过给药诱导红细胞聚集的反应 大分子右旋糖苷或通过降低红细胞变形性 通过与硬化的红细胞交换输血。WBC的平行研究 将执行以评估它们在整个 微血管网络及其隔离 可变形性和对内皮的粘附性。In的影响 化学诱导剂引起或延长的WBC的原位激活 缺血，将被研究。我们会特别注意 白细胞与毛细血管后静脉内皮细胞的选择性黏附 白细胞变形性、粘附性与细胞免疫功能的关系 血液动力学力量(剪切力)倾向于将白细胞从 静脉壁。一个主要目标将是勾勒出 白细胞在毛细血管孔内的包封率与白细胞内皮细胞的关系 粘附性影响缺血发作后的恢复。数学 还将进行建模和计算机模拟，以阐明 血细胞变形性与细胞间的相对贡献 影响微血管功能的相互作用。预计 这些研究的结果将提供对这一角色的更深入的了解 血细胞的机械和生化特性在影响 微血管功能将有助于临床治疗 各种病理生理状态，如贫血、红细胞增多症、低血压病 血流状态、休克、炎症和血细胞紊乱，仅举几例。

The overall goal of this research program 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 cell 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 induced by either mechanical intervention of the arterial inflow or hemorrhagic hypotension. Specific studies on RBCs will examine red cell sequestration and entrapment in the low flow state, in response to the induction of red cell aggregation by administration of high molecular weight dextrans or by reduction of red cell deformability by exchange transfusion with hardened RBCs. Parallel stUdies on WBCs will be performed to evaluate their distribution throughout the microvascular network and their sequestration in light of their deformability and adhesiveness to the endothelium. The effects of in situ activation of WBCS, resulting from chemoattractants or prolonged ischemia, will be studied. Particular attention will be given to the preferential adhesion of WBCs to postcapillary venular endothelium in light of the relationship between WBC deformability, adhesiveness, and hemodynamic forces (shear stresses) which tend to sweep the WBC from the venular wall. A major goal will be to delineate the relative roles of entrapment of WBCs in the capillary orifice versus WBC-endothelium adhesion in affecting recovery from ischemic episodes. Mathematical modelling and computer simulations will also be performed to elucidate the relative contributions of blood cell deformability and cell-cell interaction in affecting microvascular function. It is anticipated that the results of these studies will provide greater insight into the role of the mechanical and biochemical properties of blood cells in affecting microvascular function which will aid in the clinical management of a variety pathophysiological states such as anemia, polycythemia, the low flow state, shock, inflammation and blood cell disorders, to name a few.