STRUCTURE-FUNCTION CORRELATIONS IN TISSUE GAS EXCHANGE

总的目标是更好地了解 呼吸系统设计中的结构和功能， 外周组织（骨骼肌和心脏）。 的估计 O2扩散以及基质吸收、再分布和 输出，在肌肉纤维取决于几个形态测量 参数，包括毛细作用，模型选择来描述 O2和其他代谢物的扩散以及它们的距离 物质需要在毛细血管和线粒体之间移动 和/或肌原纤维。 自从克罗开创性地“呼吁研究 定量解剖”来模拟外周气体交换， 扩散途径分析所必需的定量数据 以及它们与最大O2摄取、组织O2需求和 环境中的O2供应要么缺乏， 争议 我们建议将形态测量估计 扩散途径（毛细血管间距，线粒体 肌纤维内的密度和分布）和毛细血管 在同一块肌肉中的几何形状。 我们将分析动物1） 在常氧条件下O2需求不同（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（哺乳动物和鸟类， 低O2混合物呼吸，并在高海拔），和3）耐受 极端缺氧（潜水海洋哺乳动物与不同的能量 鸟类适应更高的海拔）。 不同 骨骼肌（主要是有氧、糖酵解和混合肌）， 并且将在每个动物组中分析心脏。 我们的具体目标是1）确定肌肉毛细血管如何 几何形状（毛细管与纤维的比率、共享因子、毛细管 弯曲度和密度）与O2需求有关，2） 测试希尔模型比 Krogh圆柱体几何形状模拟O2供应到收缩 肌肉，3）以确定毛细血管体积和几何形状如何 与氧扩散vs底物输送和乳酸盐相关 重新分配，4）确定结构-功能关系， 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 在外围设备的设计中可能发生（或不发生）适应性变化， 组织响应有限的环境O2。 这将提供 对结构-功能理解的新见解 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.