Minority Predoctoral Fellowship Program

描述（由申请人提供）：运动不耐受、肺气体交换（O2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CHF如何影响微血管功能和在肌肉收缩开始时骨骼肌中的O2交换，此时肌肉能量（并因此O2）需求增加。Poole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，磷光淬灭），以解决这个问题。我提出的博士论文将测试CHF诱导微循环功能障碍的广泛假设，该微循环功能障碍在收缩开始时损害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人类疾病的模拟，并具有允许非常侵入性的研究，也有利于CHF动物与对照组的直接比较的主要优势。对每年超过200，000名美国人和全世界数百万人的CHF患者的有效治疗的开发取决于CHF患者的肌肉功能障碍的机制基础的解决。在这方面，我的博士工作旨在解决一个重要的潜在机制的物理限制pathognonic 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.