RHEOLOGICAL DETERMINANTS OF MICROVASCULAR FUNCTION

本研究计划的总体目标是阐明 血液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是 从直接原位测量血液动力学变量得出， 外置组织如肠系膜、网膜和提睾肌。 具体的目的是阐明血流与 单个微血管内的血细胞机械性能， 遍布微血管网的分支点和局部 贯穿于主要微血管的连续分裂。 一个主要 研究的重点将是阐明微血管功能， 低流量状态由机械干预或 动脉流入或出血性低血压。 关于RBC的特定研究 将检查红细胞在低流量状态下的隔离和截留， 响应于通过施用以下物质诱导红细胞聚集 高分子量葡聚糖或通过降低红细胞变形性 用硬化的红细胞交换输血 白细胞的平行研究 将进行评估其分布在整个 微血管网络及其隔离， 内皮的变形性和粘附性。 影响在 WBCS的原位激活，由化学引诱剂或延长 将进行研究。 将特别注意 白细胞优先粘附于毛细血管后微静脉内皮细胞， 根据WBC变形性、WBC计数和WBC计数之间的关系， 血液动力学力（剪切应力）倾向于将WBC从 微静脉壁 一个主要的目标将是划定的相对作用， 白细胞截留在毛细血管孔中与白细胞-内皮细胞 粘附影响缺血发作的恢复。 数学 还将进行建模和计算机模拟， 血细胞变形性和细胞-细胞 影响微血管功能的相互作用。 预计各国 这些研究的结果将使人们更深入地了解 血细胞的机械和生物化学特性 微血管功能，这将有助于临床管理 各种病理生理状态，如贫血、红细胞增多症、低血糖 流动状态、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.