METABOLIC CONSEQUENCES OF ERYTHROCYTE TRANSFUSION IN SICKLE CELL ANEMIA

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。假设：镰状细胞性贫血（SCA）中伴随慢性红细胞输注（TR）的代谢事件的顺序尚不清楚。虽然有报道称SCA中静息能量消耗（EE）和蛋白质周转增加，但其潜在的生理机制尚不完全清楚。本研究的生理基础是，血管内体积增加、红细胞活性降低、血液粘度增加以及激素活性的变化共同导致能量代谢和蛋白质周转的变化。本GCRC方案的中心假设是静息能量消耗和全身蛋白质代谢在单次TR后会减少，重复TR后也会有类似的效果。具体目标：中心假设将通过追求以下具体目标来验证：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代谢。工作假设是，单次TR后脂肪代谢成分和全身蛋白质周转减少，重复TR后效果相似。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.