This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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