DETERMINANTS OF MAXIMUM OXYGEN UPTAKE

总的目标仍然是阐明限制 运输O2从大气中的线粒体在健康和 疾病 本建议继续进一步探讨关键方面， O2运输限制。 在此期间，我们开发了一个 理论分析O2供应限制最大Vo2的依据， 在离体犬腓肠肌中进行了多次测试 准备，并将其应用于正常人。我们已经开始扩展的 基本理论，以更好地理解不同的相对重要性 影响O2通过运输途径移动的步骤。 在这 一个值得注意的新方向是关注人类疾病，如慢性疾病， 心力衰竭（CHF）和慢性阻塞性肺病（COPD），以及 也用于急性和慢性疾病的动物模型。 在这里，我们将应用 上一个赠款周期的经验教训，以更好地了解 常见严重人类疾病中运动和O2运输的限制 国家的预期，更好的理解将最终 转化为更好的护理。 其他新的方向是使用组合 生理和分子方法来研究正常反应， 肌肉毛细血管耐力训练和使用血红蛋白溶液 探讨骨骼肌有限氧卸载的机制。 我们 还计划（协作）方法开发组件，包括 微血管血浆P02和1H磁共振波谱，以评估 肌红蛋白氧饱和度 像往常一样，我们有目的地将联合收割机和 人类研究与理论建模的信念，每一个 这些要素对于成功的研究计划至关重要， 彼此，使整体超过其部分之和。

The overall goal remains the elucidation of mechanisms that limit the transport of O2 from the atmosphere to the mitochondria in both health and disease. The present proposal continues f to further explore key aspects of O2 transport limitation. During this time, we have developed a theoretical analysis of the basis for O2 supply limitation of maximum Vo2, tested it in many situations in the isolated canine gastrocnemius preparation, and applied it in normal man. We have begun extensions of the basic theory to better understand the relative importance of different steps in affecting O2 movement through the transport pathway. In this proposal, a notable new direction focuses on human diseases such as chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD), and also on animal models of acute and chronic diseases. Here we will apply the lessons learned during the previous grant cycle to better understand limitations to exercise and O2 transport in common serious human disease states with the anticipation that a better understanding will ultimately translate into improved care. Other new directions are to use combinations of physiological, and molecular approaches to study the normal response of the muscle capillary to endurance training and to use hemoglobin solutions to pursue the mechanisms of limited O2 unloading in skeletal muscle. We also plan (collaborative) method development components involving microvascular plasma P02 and 1H magnetic resonance spectroscopy to assess myoglobin O2 saturation. As always, we purposefully combine animal and human research with theoretical modelling on the conviction that each of these elements is essential to a successful research program, enriching each other so that the whole exceeds the sum of its parts.