STRUCTURE - FUNCTION CORRELATIONS IN TISSUE GAS EXCHANGE

外周组织气体交换过程中的关键问题 水平仍然知之甚少。 定量数据对 分析扩散途径，如毛细作用（O2供应）， 不同的肌肉，及其与最大O2摄取，环境O2 可用性和O2需求（肌肉细胞的氧化能力）已被 失踪或有争议。 我建议采用一种方法， 开发用于估计各向异性结构的长度密度， 骨骼肌中的毛细血管，以量化骨骼肌中的毛细血管网络。 具有不同O2需求和/或暴露于 不同的环境O2可用性，我将分析动物1） 不同的O2需求在常氧条件下（陆地哺乳动物， 不同的大小和性能;爬行动物;鸟类），2）暴露于急性和 慢性缺氧（大鼠给予低O2混合物呼吸， 海拔），和3）耐受极端缺氧（潜水海洋哺乳动物与 不同的能量需求;鸟类适应更高的海拔）。 的 毛细管网络的测量将与 线粒体室和纤维大小的比较分析 在相同的样本中。 不同的骨骼肌（主要是有氧， 糖酵解和混合肌肉）和心脏（与工作率的相关性） 将在每个动物组中进行分析。 我的具体目标是确定：1）结构-功能关系， 从肌肉中的线粒体设计呼吸系统（主要 O2消耗部位），超过肌纤维尺寸（O2扩散途径）， 心脏和骨骼肌中的肌肉毛细血管（O2供应）， 不同的动物模型，以及2）评估哪些适应性变化可以 发生（或不发生）在外周组织的呼吸系统设计中 以应对有限的环境O2。 这将提供新的见解， 对组织气体结构-功能相关性的理解 交流，并可能有助于了解人类对 低氧血症。

Critical aspects in the process of gas exchange at the peripheral tissue level are still poorly understood. Quantitative data essential to the analysis of diffusion pathways, such as capillarity (O2 supply) in different muscles, and its relation to maximal O2 uptake, environmental O2 availability and O2 demand (muscle cells oxidative capacity) have been either missing or controversial. I propose to apply a method we recently developed to estimate the length density of anisotropic structures, capillaries in skeletal muscles to quantify the capillary network in muscles of animals with different O2 requirements and/or exposed to different environmental O2 availability, I will analyse 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 (rats given low O2 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). The measurements of the capillary network will be correlated with the comparative analysis of the size of the mitochondrial compartment and fiber size in the same samples. Different skeletal muscles (mostly aerobic, glycolytic and mixed muscles), and the heart (correlation with work rate) will be analysed in each animal group. My specific aims are to determine: 1) structure-function relationships in the design of the respiratory system from mitochondria in muscles (main site of O2 consumption), over muscle fiber size (O2 diffusion pathways), to muscle capillaries (O2 supply) in the heart and skeletal muscles in different animal models, and 2) to evaluate which adaptative changes can occur (or not) in the design of the respiratory system 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.