OXYGEN AFFINITY AND OXYGEN TRANSPORT IN STRIATED MUSCLE

该项目的总体目标是提供所需的重要信息 制定新的概念框架， 氧气供应到组织的机制。目前的概念是 Krogh的简单模型的基本上轻微的修改， 毛细管供应特定的组织圆柱体（25）。虽然他的模型 提供了一个有用的开始，氧气供应的几个重要方面， 被忽视了。我们最近观察到大量的氧气交换 在微血管（14，45）是在显着对比克罗的想法， 毛细血管是氧气供应的唯一来源。另外虽然 血液和组织之间的氧张力梯度对于 氧转移，它可能不是唯一的因素负责 组织的充分氧合。因此，必须改变 我们的概念框架。我们必须进一步调查 负责维持在宽的氧气供应的机制 条件的范围。 本研究拟对两个假设进行检验。首先是氧气 含量是氧交换的重要调节剂， 氧气供应相对于需求而言非常有限。第二是 一种机制是在宽的呼吸道下维持对组织的氧气供应， 条件范围内，是通过改变扩散的局部化， 氧气输送 实验将在仓鼠颊囊牵开肌中进行。 我们将利用氧合血红蛋白解离曲线的左移 （通过长期短期给予氰酸钠实现）， 改变氧张力和氧含量之间的关系。这 血红蛋白氧亲和力的变化沿着全身缺氧， 等容血液稀释将提供宽范围的氧气供应 这些条件使我们能够具体地解决我们的假设。数据 毛细血管氧转运，血流动力学和氧合参数 将在毛细管网络内的特定位置获得， 活体视频显微镜与计算机辅助图像分析技术。在 结合毛细管数据， 在前和后毛细血管网络的氧合将获得使用 荧光标记的红细胞和PO2微电极 在小动脉壁上或在一级动脉内 和小静脉，这取决于所处理的具体目的。这些研究 将提供各种相互作用机制的重要信息， 负责在广泛的环境下向组织提供充足的氧气， 氧气供应条件的光谱。我们对这些的理解 机制将不仅为我们提供一个更好的概念图片， 组织氧合，但将有助于我们了解的因素， 导致外周氧利用率受损 临床上遇到的。

The overall goal of this project is to provide vital information required for the formulation of a new conceptual framework for understanding the mechanisms by which oxygen is supplied to tissue. The current concepts are essentially slight modifications of Krogh's simplistic model of a single capillary supplying a specific cylinder of tissue (25). While his model provides a useful beginning, several important aspects of oxygen supply are neglected. Our recent observations of considerable oxygen exchange among microvessels (14,45) is in marked contrast to Krogh's idea of the capillaries being the sole source of oxygen supply. In addition, although the oxygen tension gradient between blood and tissue is important for oxygen transfer, it may not be the sole factor responsible for the adequate oxygenation of the tissue. It thus becomes imperative to change our conceptual framework. We must further investigate the numerous complex mechanisms responsible for the maintenance of oxygen supply under a broad range of conditions. Two hypotheses are to be tested in this project. The first is that oxygen content is an important regulator of oxygen exchange under conditions of a severely limited oxygen supply relative to demand. The second is that one mechanism by which oxygen supply to tissue is maintained under a wide range of conditions, is by an alteration in the localization of diffusive oxygen transfer. Experiments will be performed in the hamster cheek pouch retractor muscle. We will utilize a left-shift of the oxyhemoglobin dissociation curve (achieved by the chronic, short-term administration of sodium cyanate) to alter the relationship between oxygen tension and oxygen content. This change in hemoglobin oxygen affinity along with systemic hypoxia and isovolemic hemodilution will provide a broad range of oxygen supply conditions enabling us to specifically address our hypotheses. Data on capillary oxygen transport, both hemodynamic and oxygenation parameters will be obtained at specific locations within the capillary network using Ln vivo video microscopy and computer-aided image analysis techniques. In conjunction with the capillary data, information on the levels of oxygenation in the pre and postcapillary network will be obtained using fluorescently labeled red blood cells and PO2 microelectrodes positioned either on the wall of small arterioles or within first order arterioles and venules depending on the specific aim being addressed. These studies will provide vital information on the various interacting mechanisms responsible for the adequate supply of oxygen to tissue under a broad spectrum of oxygen supply conditions. Our understanding of these mechanisms will not only provide us with a better conceptual picture of tissue oxygenation but will aid our understanding of the factors responsible for the impairment in peripheral oxygen utilization frequently encountered clinically.