STRUCTURE-FUNCTION CORRELATIONS IN TISSUE GAS EXCHANGE

总体目标是更好地了解 呼吸系统设计中的结构与功能 外周组织(骨骼肌和心脏)。的估算 O2扩散以及底物吸收、再分配和 产量，在肌肉纤维中取决于几种形态测量 参数，包括毛细作用，所选择的模型来描述 氧气和其他代谢物的扩散，以及这些距离 物质需要在毛细血管和线粒体之间移动。 和/或肌原纤维。自从克罗的开创性的《恳求研究 为了模拟外周气体交换， 对扩散路径分析至关重要的定量数据 以及它们与最大氧气摄取量、组织氧气需求和 环境中氧气的可用性要么缺乏，要么 有争议的。我们建议将形态计量估计关联起来 扩散途径(毛细血管间距离、线粒体 肌纤维内的密度和分布)和毛细血管 同一块肌肉中的几何图形。我们将分析动物 常氧条件下氧气需求的不同(陆地 不同大小和性能的哺乳动物；爬行动物；鸟类)，2) 暴露于急性和慢性缺氧(给予哺乳动物和鸟类 低O2混合物呼吸，在高海拔)，以及3)耐受性 极度缺氧(潜水的海洋哺乳动物以不同的能量 要求；鸟类适应较高的海拔)。不同 骨骼肌(主要是有氧肌、糖酵解肌和混合肌)， 并对每组动物的心脏进行分析。 我们的具体目标是：1)确定肌肉毛细血管 几何形状(毛细纤维比、共享系数、毛细管 吻合口的弯曲度和密度)与氧气需求有关，2) 检验Hill模型比其他模型更合适的假设 用于模拟收缩供氧的克罗圆柱体几何 肌肉，3)确定毛细血管体积和几何形状 与氧扩散与底物输送和乳酸有关 重新分配，4)确定结构-功能关系 运动中肌肉呼吸系统的设计 哺乳动物、爬行动物和鸟类模型，以及5)评估哪种 在外围设备的设计中可以发生(或不发生)适应性变化 组织对有限的环境氧气的反应。这将提供 对结构-功能认识的新认识 组织气体交换的相关性，并可能有助于 了解人类对低氧血症的反应。

The overall objective is to better understand the interaction of structure and function in the design of the respiratory system in peripheral tissue (skeletal muscle and heart). The estimation of O2 diffusion, as well as substrate uptake, redistribution and output, in the muscle fibers depends on several morphometric parameters including capillarity, the model chosen to describe the diffusion of O2 and other metabolites, and the distances these substances need to travel between capillaries and mitochondria and/or myofibrils. Since Krogh's pioneering "plea for the study of quantitative anatomy" to model peripheral gas exchange, quantitative data essential to the analysis of diffusion pathways and their relation to maximal O2 uptake, tissue O2 demand, and the environmental O2 availability have been either lacking or controversial. We propose to correlate morphometric estimates of diffusion pathways (intercapillary distances, mitochondrial density and distribution within the muscle fibers) and capillary geometry in the same muscles. We will analyze animals 1) differing in O2 demand in normoxic conditions (terrestrial mammals of different size and performance; reptiles; birds), 2) exposed to acute and chronic hypoxia (mammals and birds given low 02 mixtures to breathe, and at high altitude), and 3) tolerant to extreme anoxia (diving marine mammals with different energy requirements; birds acclimated to higher altitude). Different skeletal muscles (mostly aerobic, glycolytic and mixed muscles), and the heart will be analyzed in each animal group. Our specific aims are 1) to determine how muscle capillary geometry (capillary to fiber ratio, sharing factor, capillary sinuosity and density of anastomoses) is related to O2 needs, 2) to test the hypothesis that the Hill model is more appropriate than the Krogh cylinder geometry to model O2 supply to contracting muscles, 3) to determine how capillary volume and geometry are related to to oxygen diffusion vs substrate delivery and lactate redistribution, 4) to determine structure-function relationships in the design of the respiratory system of muscles in the mammalian, reptile and bird models, and 5) to evaluate which adaptative changes can occur (or not) in the design of peripheral tissue in response to limited environmental O2. This will provide new insights in the understanding of structure-function correlations in tissue gas-exchange, and possibly help in the understanding of human response to hypoxemia.