STRUCTURE-FUNCTION CORRELATIONS IN TISSUE GAS EXCHANGE

其目标是更好地理解结构与功能之间的相互作用 肌肉用于血液和组织交换的设计和能力。在 在之前的周期中，我们开发了评估肌肉的几个方面的方法 毛细纤维形态计量学。我们建议将这些方法结合使用 具有纤维类型和毛细血管的组织化学特征 继续探索肌肉对O2的结构能力的异质性 流量，并研究其极限(S)和塑性与纤维需求和 分发。我们的研究将主要集中在大鼠的肌肉上， 兔、蝙蝠飞行肌肉和蝙蝠特定肌肉的特异性比较 鸟类，以利用纤维类型组成的天然差异或 聚集、毛细血管几何形状和功能限制。我们的特定 目的是：1)评估肌肉对氧气的结构能力上限 从毛细血管到纤维线粒体的流量，2)决定聚集表面 可用于扩散的膜区域a)从毛细管径向扩散到 肌纤维，以及b)动静脉毛细血管通路，3) 评估纤维型血管形成和内部结构的异质性 和肌肉之间，4)比较有氧功能的结构潜力 在毛细血管纤维结构差异较大的肌肉中 功能需求(鸟类与哺乳动物；飞行肌肉与后肢)；以及 评估毛细纤维几何形状的可塑性以响应5) 慢性活动增加和6)慢性缺氧。 我们将检验以下假设：1)毛细纤维的大小 界面决定有氧肌肉的氧通量速率，2)压力 驱动最大氧气通量速率所需的梯度与 膜表面积可用于从毛细管扩散到 线粒体酶，3)纤维血管化的差异和 肌肉之间的结构大于肌肉内的结构，4)纤维结构 鸟类和哺乳动物肌肉中的血管模式与 功能需求和限制，5)随着光纤氧气需求的增加 活性增加，毛细血管-纤维界面和 线粒体膜表面积的聚集对于建立 限制氧气的输送和利用，以及6)毛细血管的大小- 纤维界面相对于纤维线粒体体积增加 对慢性低氧的反应，允许足够的氧气通量速率 维持在较低的毛细血管血氧饱和度。这将提供新的 对结构-功能关键方面理解的见解 肌肉对血液组织转移能力的相关性应该会有所帮助 在理解和管理人类对低氧血症的反应方面。

The objective is to better understand structure-function interactions in the design and capacity of muscles for blood-tissue exchange. In the previous cycle, we developed methods to assess several aspects of muscle capillary-fiber morphometrics. We propose to use these methods together with histochemical characterization of fiber type and capillary heterogeneities to continue to explore muscle structural capacity for O2 flux, and study its limit(s) and plasticity in relation to fiber demand and distribution. Our studies will mainly focus on muscles of rats, with specific comparison in rabbit, flight muscle of bat and specific muscles of birds, to exploit natural differences in fiber type composition or clustering, capillary geometry and functional constraints. Our specific aims are 1) to assess the upper limits of muscle structural capacity for O2 flux from capillary to fiber mitochondria, 2) determine aggregate surface areas of membranes available for diffusion a) radially from capillary into the muscle fibers, and b) along the arterio-venous capillary path, 3) estimate heterogeneities in fiber type vascularization and structure within and between muscles, 4) compare structural potentials for aerobic function in muscles with large differences in capillary-fiber structure and functional requirements (bird vs mammals; flight muscle vs hindlimb), and assess the plasticity of capillary-fiber geometry in response to 5) chronically increased activity and 6) chronic hypoxia. We will test the hypotheses that 1) the size of the capillary-fiber interface determines O2 flux rates in aerobic muscles, 2) pressure gradients required to drive maximal O2 flux rates are inversely related to membrane surface areas available for diffusion from capillary to mitochondrial enzymes, 3) differences in fiber vascularization and structure are greater between than within muscles, 4) fiber structure and vascularization patterns in muscles of birds and mammals are related to functional demands and constraints, 5) as fiber O2 demand increases with increased activity, the ratio between capillary-fiber interface and aggregate mitochondrial membrane surface areas is critical to establish the limit to O2 delivery and utilization, and 6) the size of the capillary- fiber interface relative to fiber mitochondrial volume increases in response to chronic hypoxia, allowing adequate O2 flux rates to be maintained, at lower Po2 in the capillaries. This will provide new insights in the understanding of key aspects of structure-function correlations in muscle capacity for blood-tissue transfer and should help in the understanding and management of human response to hypoxemia.