Minority Predoctoral Fellowship Program

描述（由申请人提供）：运动不耐受、肺气体交换（02摄取）动力学减慢和骨骼肌功能障碍是CHF患者的特征。迄今为止，尚不清楚当肌肉能量（因此02）需求增加时，CHF如何影响肌肉收缩开始时骨骼肌的微血管功能和02交换。普尔博士的实验室已经组装了一个独特的组合建立和国家的最先进的技术（活体显微镜，磷光猝灭）来解决这个问题。我提出的博士论文将测试一个广泛的假设，即心力衰竭会导致微循环功能障碍，从而损害02在收缩开始时从血液到肌肉的转移。这项工作将利用大鼠慢性心力衰竭模型，这是一种被广泛接受的模拟人类病情的模型，其主要优点是允许进行非常侵入性的研究，也便于将慢性心力衰竭动物与对照组进行直接比较。针对每年超过20万美国人和全世界数百万CHF患者的有效治疗方案的开发取决于对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物理限制病理性的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.