METABOLIC CONSEQUENCES OF ERYTHROCYTE TRANSFUSION IN SICKLE CELL ANEMIA

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。假设：镰状细胞性贫血（SCA）中伴随慢性红细胞输注（TR）的代谢事件顺序尚不清楚。虽然已有研究表明SCA可增加静息能量消耗和蛋白质周转，但其生理机制尚不完全清楚。拟议研究的生理基础是血管内容量增加，红细胞活性降低，血液粘度增加和激素活性变化可能共同导致能量代谢和蛋白质周转的变化。该GCRC方案的中心假设是，在单次TR后，静息能量消耗和全身蛋白质周转将降低，并且在重复TR后，该效应将相似。具体目标：中心假设将通过追求以下具体目标进行检验：1）确定单次和重复TR如何影响SCA青少年的能量消耗和蛋白质周转。工作假设是，EE和全身蛋白质周转的组成部分将在单次TR后降低，重复TR后这种效果将相似。2)确定TR后能量和蛋白质代谢变化的潜在生理机制。

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. HYPOTHESIS: The sequence of metabolic events accompanying chronic erythrocyte transfusions (TR) in sickle cell anemia (SCA) is unknown. Although it has been reported that resting energy expenditure (EE) and protein turnover are increased in SCA, underlying physiological mechanism(s) are not completely understood. The physiological basis for the proposed research is that increased intravascular volume, decreased erythrocyte activity, increased blood viscosity, and changes in hormonal activity could collectively contribute to changes in energy metabolism and protein turnover. The central hypothesis of this GCRC protocol is that resting energy expenditure and whole body protein turnover will decrease following a single TR, and this effect will be similar after repeated TR. SPECIFIC AIMS: The central hypothesis will be tested by pursuing the following specific aims: 1) Determine how single and repeated TR affect energy expenditure and protein turnover in SCA adolescents. The working hypothesis is that components of EE and whole body protein turnover will decrease following single TR and this effect will be similar after repeated TR. 2) Identify underlying physiological mechanisms responsible for changes in energy and protein metabolism following TR.