METABOLIC CONSEQUENCES OF ERYTHROCYTE TRANSFUSION IN SICKLE CELL ANEMIA

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。假设：镰状细胞性贫血(SCA)患者伴随慢性红细胞输注(TR)的代谢事件序列尚不清楚。尽管已有报道表明SCA患者的静息能量消耗(EE)和蛋白质周转增加，但其潜在的生理机制(S)还不完全清楚。这项研究的生理学基础是，血管内容量的增加、红细胞活性的降低、血液粘度的增加以及激素活性的变化可能共同导致能量代谢和蛋白质周转的变化。这一GCRC方案的中心假设是，静息能量消耗和全身蛋白质周转在单次tr后会下降，重复tr后这种影响将是相似的。具体目标：将通过追求以下具体目标来检验中心假设：1)确定单一和重复的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的成分和全身蛋白质的周转率在单次TR后会下降，这种影响在重复TR后将是相似的。2)找出导致肝移植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.