RHEOLOGICAL DETERMINANTS OF MICROVASCULAR FUNCTION

这项提议的主旨是阐明血液的作用。 流变学作为健康和健康人群微血管功能的决定因素 疾病。活体显微镜技术将应用于 检测影响血液阻力的流变学因素 在麻醉动物体内的生物物理流动 红细胞和白细胞在微血管中的行为 大小从100亩到真正的毛细血管，5-7亩在 直径。微血管功能的检查将参照 血细胞浓度和变形性，红细胞聚集， 白细胞与血管内皮细胞的黏附。为此， 将研究肠系膜、大网膜的血流动力学。 和Cremaster肌肉网络，以得出量化指标 微血管功能：红细胞速度、压力 梯度、血细胞分布和浓度以及 血红蛋白血氧饱和度。正常血液和异常血液 流变学将在分支的单个微血管中进行检查。 网络内的点和整个区域连续的点 微血管分裂。建议进行研究以检查 灌流：(1)正常血细胞，(2)在原位 通过化学试剂操纵血细胞特性，例如 右旋糖苷诱导红细胞聚集或趋化物质 诱导白细胞与内皮细胞黏附，以及(3)在 引入具有异常性质的血细胞，如通过 用戊二醛硬化的红细胞的等容交换，或 注入不正常的白细胞。此外，从 微血管内径调节对微血管影响的观察 诱导病理流变学--代偿性疾病的描述 将进行血管舒缩调整，以获得更清晰的 对影响组织的流变性过程的了解 灌流。在这些动物研究的同时，平行研究 将被用来检查皮肤中的毛细血管血流 (甲皱)血液系统疾病的受试者。 数学建模与计算机仿真 微血管血流也将进行，以获得一个 综合看待血液流变学与中医辨证论治的关系 微血管功能。预计这些措施的结果 研究将为我们更深入地了解 微血管功能的血液流变学决定因素 将有助于临床管理各种不同的 贫血、红细胞增多症、低血压病等病理生理状态 血流状态、炎症和血细胞紊乱，仅举几例。

The major thrust of this proposal is to elucidate the role of blood rheology as a determinant of microvascular function in health and disease. Techniques of intravital microscopy will be applied to examine rheological factors which affect the resistance to blood flow in the anesthetized animal in terms of the biophysical behavior of erythrocytes and leukocytes in microvessels ranging in size from 100 Mu down to the true capillaries, 5-7 mu in diameter. Microvascular function will be examined in light of blood cell concentration and deformability, red cell aggregation, and leukocyte adhesion to the endothelium. To this end, hemodynamics will be studied in intestinal mesentery, omentum and cremaster muscle networks to derive quantitative indices of microvascular function in terms of: red cell velocity, pressure gradients, blood cell distribution and concentrations and hemoglobin oxygen saturation. Normal and abnormal blood rheology will be examined in individual microvessels, at branch points within a network and regionally throughout successive microvascular divisions. Studies are proposed to examine perfusion with: (1) normal blood cells, (2) during the in situ manipulation of blood cell properties by chemical reagents, e.g. dextrans to induce red cell aggregation or chemoattractants to elicit leukocyte to endothelium adhesion, and (3) following the introduction of blood cells with abnormal properties, such as by isovolemic exchange of red cells rigidified with glutaraldehyde, or a bolus infusion of abnormal leukocytes. In addition, from observations of microvessel diameter adjustments in response to the induced pathorheology, a delineation of compensatory vasomotor adjustments will be made to gain a clearer understanding of those rheological processes which affect tissue perfusion. In concert with these animal studies, parallel studies will be conducted to examine capillary blood flow in the skin (nailfold) of human subjects with hematological disorders. Mathematical modelling and computer simulations of microvascular blood flow will also be performed to gain an integrated view of the relationship between blood rheology and microvascular function. It is anticipated that the results of these studies will provide greater insight into the role of hemorheological determinants of microvascular function which will aid in the clinical management of a variety of pathophysiological states such as anemia, polycythemia, the low flow state, inflammation and blood cell disorders, to name a few.