NON-INVASIVE MICROCIRCULATORY MONITORING IN SICKLE CELL DISEASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究建议调查几种新的非侵入性监测系统的使用情况，这些系统允许对微循环系统进行成像和定量评估。我们还建议描述这些反应的特征，并将它们与镰状细胞血管闭塞症患者的危机状态状况相关联。 镰状细胞病是一种遗传性常染色体隐性遗传性疾病，在美国的非洲血统人群中很常见。在全球范围内，地中海人、印度人和沙特阿拉伯人的后裔中也发现了这种疾病。镰状细胞病的基因导致贝塔链氨基末端第六位的谷氨酸被缬氨酸取代。生理效应是一种溶血性贫血，伴有血管闭塞，可导致局部缺血，导致疼痛和器官损害。血管闭塞发作会导致疼痛和慢性器官衰竭，预测早期死亡，更重要的是与这一人群中的大多数医疗接触有关。已有文献表明，镰状细胞病是微循环水平上一个复杂的多因素过程。炎症细胞因子的复杂相互作用、RBC和RBC的相互作用、RBC和WBC的黏附、局部组织缺血和疼痛都与微循环障碍有关。8过去在人类活体模型中研究镰状细胞所需的工具有限。然而，新技术的出现，旨在对微循环进行成像并量化某些方面的氧气运输，以确定局部缺血的存在，可能使这一点变得更加可能。这些新的非侵入性技术为深入了解一种复杂的慢性疾病提供了独特的机会。观察微循环过程，并将其与患者之间和患者内部的疼痛主观评估进行比较，将为进一步研究提供新的途径。使用非侵入性技术评估微循环的人体模型研究有限。 对处于非危象状态和危急状态的患者进行监测，并进行血流动力学测量。将获得几个结果指标，包括全身动脉血氧饱和度(通过脉搏血氧饱和度)，HGB浓度(通过标准的实验室工作)，红细胞速度，功能性毛细血管密度，激光多普勒组织血流量，组织血红蛋白氧饱和度，经皮氧和二氧化碳浓度，心输出量，氧消耗。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study proposes to investigate the utilization of several new non-invasive monitoring systems that allow the imaging and quantitative assessment of the microcirculatory system. We also propose to characterize these reactions and correlate them to crisis state conditions in patients with Sickle Cell Vaso-Occlusive Disease. Sickle cell disease is an inherited autotsomal recessive disorder that is common to persons of African ancestry within the United States. Globally, the disorder is also found in persons of Mediterranean, Indian, and Saudi Arabian descent. The gene for sickle cell disease results in the substitution of valine for glutamic acid in the sixth position of the amino terminus of the Beta chain. The physiologic effect is a hemolytic anemia accompanied by vaso-occlusion that can cause local ischemia and lead to pain and organ damage. Vaso-occlusive episodes cause pain and chronic organ failure, predict early mortality, and more responsible for the majority of medical contacts in this population. It is well documented that sickle cell disease is a complex multifactorial process on a microcirculatory level. The complex interaction of inflammatory cytokines, RBC and RBC interaction, RBC and WBC adhesion, local tissue ischemia, and pain all relate to a microcirculatory dysfunction.8 The tools required to study sickle cell in human in-vivo models has been limited in the past. However, the advent of new technology designed to image the microcirculation and quantify certain aspects oxygen transport to determine the presence of local ischemia may make this more possible. These novel non-invasive techniques provide a unique opportunity to gain insight into a complex chronic disorder. To observe the microcirculatory process and compare it to subjective assessment of pain both between and within patients will provide new avenues for further studies. There is limited research on human models using non-invasive techniques to Asses the microcirculation. Patients will be monitored in non-crisis state and in crisis state of the disease and hemodynamic measurements will be made. Several outcome measures will be obtained, these include systemic arterial hemoglobin oxygen saturation (via pulse oximetry), Hgb concentration (by standard lab work), red blood cell velocity, functional capillary density, laser Doppler tissue blood flow, tissue hemoglobin oxygen saturation, transcutaneous oxygen and carbon dioxide concentrations, cardiac output, oxygen consumption.