RHEOLOGICAL DETERMINANTS OF MICROVASCULAR FUNCTION

这项建议的主旨是阐明血液的作用 流变学作为健康微血管功能的决定因素， 疾病 活体显微镜技术将应用于 检查影响血液阻力的流变学因素 在生物物理方面， 红细胞和白细胞在微血管中的行为， 大小从100亩下降到真正的毛细血管，5-7亩， 直径. 微血管功能将根据 血细胞浓度和变形性，红细胞聚集， 以及白细胞粘附于内皮。 为此目的， 将在肠肠系膜、网膜中研究血液动力学 和提睾肌网络，以获得 微血管功能：红细胞流速、压力 梯度、血细胞分布和浓度， 血氧饱和度 正常和异常血液 将在分支的单个微血管中检查流变学 网络内的点和区域性的连续 微血管分裂 建议进行研究， 灌注：（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 葡聚糖诱导红细胞聚集或化学引诱剂， 诱导白细胞与内皮细胞粘附，以及（3）在 引入具有异常性质的血细胞，例如通过 用戊二醛硬化的红细胞的等容交换，或 一次注射不正常的白细胞 另外从 微血管直径调整的观察结果 诱导的病理流变学， 将进行大量调整，以获得更清晰的 了解影响组织的流变过程 灌注。 与这些动物研究一致，平行研究 将进行皮肤毛细血管血流检查 （甲襞）。 数学建模和计算机模拟 微血管血流也将进行，以获得 血液流变学与血液流变学之间关系的综合观点 微血管功能 预计，这些结果 研究将提供更深入的了解的作用， 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 病理生理状态，如贫血、红细胞增多症、低 流动状态、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.