Blood Flow and Rheology in the Micorcirculation

描述(申请人提供)：这项研究的目的是确定血液的流变性在正常情况下和在疾病中对微循环和组织功能的影响。在我们以前的研究中，我们重点研究了红细胞聚集影响微循环网络功能的过程，特别是静脉微循环的功能。在接下来的资助期间，我们将扩大我们的研究范围，更广泛地研究血液的流变性如何影响循环系统的功能。一个方面是考虑红细胞和血浆在微循环血管中发生的相分离过程。现有的实验和理论结果表明，无细胞层可能显著影响微血管调节，作为壁切应力和内皮释放NO的决定因素，以及血流红细胞核心中的血红蛋白清除NO的程度。我们将通过双重微压测量来确定微循环血管的壁面剪应力，并检测细胞自由层宽度、红细胞压积和流速变化时的剪应力。我们将主要通过光学测量来研究确定壁面剪应力的可能性。我们将直接测量红细胞自由层宽度、壁切应力和清除能力的变化对微循环血管中NO水平的影响。在毛细血管网络水平上，我们将研究相分离对具有红细胞流动的毛细血管比例(功能性毛细血管密度，FCD)和向组织输送氧气的影响。我们研究的一个主要重点将是检查疾病状态下血液流动特性的变化如何影响微循环的功能，进而影响它们所支持的组织。我们将检查贫血、红细胞增多症、红细胞刚性增加的影响，就像败血症和其他病理生理状态一样。我们的目的是对生物物理因素对微血液流变学的贡献以及这些微流变学特性如何影响微循环的调节及其在健康和疾病中的功能形成一个综合的观点。在公共健康方面，这些研究将更好地了解红细胞的物理性质在疾病状态下是如何变化的，以及这些变化反过来如何影响身体的功能。

DESCRIPTION (provided by applicant): The purpose of this study is to determine the influence of the rheological properties of blood on microcirculatory and tissue function in normal circumstances and in disease. In our previous studies we focused on the processes by which red cell aggregation affects the function of the microcirculatory network, particularly that of the venous microcirculation. For the coming grant period we will expand our studies to consider more broadly how the rheological properties of blood influence function of the circulatory system. One aspect will be to consider the process of phase separation of red cells and plasma as it occurs in the microcirculatory vessels. Available experimental and theoretical findings suggest that the cell-free layer may significantly influence microvascular regulation as a determinant of wall shear stress and NO release by the endothelium, as well as the degree of NO scavenging by hemoglobin in the red cell core of the flow stream. We will determine the wall shear stress in microcirculatory vessels by dual micropressure measurements and examine shear stress during variations in cell free layer width, hematocrit and flow rate. We will investigate the potential for determining wall shear stress principally from optical measurements. We will directly measure the effect of variations in cell free layer width, wall shear stress and scavenging capacity of the red blood cells on NO levels in microcirculatory vessels. At the capillary network level we will study the effects of phase separation on the fraction of capillaries with red cell flow (functional capillary density, FCD), and O2 delivery to tissues. A major emphasis of our studies will be to examine how changes in the flow properties of blood in disease states affects the function of the microcirculation and in turn the tissues that they support. We will examine the effects of anemia, polycythemia, increased red cell rigidity as occurs in septicemia and other pathophysiological states. Our aim is to develop an integrated view of the contribution of biophysical factors to microhemorheology and how these microrheological properties affect the regulation of the microcirculation and its function both in health and disease. In relation to public health, these studies will provide a greater appreciation of how the physical properties of the red cells are changed in disease states and how these changes in turn affect the function of the body.