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STRUCTURE-FUNCTION CORRELATIONS IN TISSUE GAS EXCHANGE

组织气体交换中的结构-功能相关性

基本信息

批准号：
3357061
负责人：
ODILE A MATHIEU-COSTELLO
金额：
$ 10.23万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-03-01 至 1990-02-28
项目状态：
已结题

项目摘要

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.

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。