Minority Predoctoral Fellowship Program

描述(申请人提供)：运动不耐受、肺气体交换减慢(摄取O2)动力学和骨骼肌功能障碍是慢性心力衰竭患者的特征。到目前为止，尚不清楚当肌肉能量需求增加时，CHF如何影响肌肉收缩开始时的微血管功能和骨骼肌中的O2交换。普尔博士的实验室已经将成熟的和最先进的技术(活体显微镜、磷光猝灭)结合在一起来解决这个问题。我提议的博士论文将测试一个广泛的假设，即CHF导致微循环功能障碍，从而在宫缩开始时损害O2从血液到肌肉的转移。这项工作将利用CHF的大鼠模型，这是一种被广泛接受的与人类情况类似的模型，具有允许进行非常侵入性研究的主要优势，也有利于CHF动物与对照组的直接比较。针对每年超过20万美国人和全球数百万的CHF患者开发有效的治疗方法，取决于CHF患者肌肉功能障碍的机制基础的解决。在这方面，我的博士工作试图解决一个重要的潜在机制的身体限制病因学的CHF。

DESCRIPTION (provided by applicant): Exercise intolerance, slowed pulmonary gas exchange (02 uptake) kinetics, and skeletal muscle dysfunction are characteristic of patients suffering from CHF. To date, it is not known how CHF impacts microvascular function and 02 exchange in skeletal muscle at the start of muscle contractions when the muscle energy (and therefore 02) demands are increased. Dr. Poole's laboratory has assembled a unique combination of established and state-of-the art techniques (intravital microscopy, phosphorescence quenching) to address this problem. My proposed doctoral thesis will test the broad hypothesis that CHF induces microcirculatory dysfunction that impairs 02 transfer from blood to muscle across the onset of contractions. This work will utilize the rat model of CHF that is a widely accepted analog of the human condition and has the major advantages of permitting very invasive studies and also facilitating direct comparison of CHF animals with controls. Development of effective treatments for CHF patients who number over 200,000 Americans per year and millions worldwide is contingent upon resolution of the mechanistic bases for the muscle dysfunction of the CHF patient. In this regard, my doctoral work seeks to address one important potential mechanism for the physical limitations pathognomonic to CHF.