OXYGEN AFFINITY AND OXYGEN TRANSPORT IN STRIATED MUSCLE

横纹肌中的氧亲和力和氧输送

• 批准号: 2219214
• 负责人: MARY L ELLSWORTH
• 金额: $ 6.75万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-01 至 1997-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2219214
• 关键词: arterioles; cheek pouch technique; diffusion; erythrocytes; hamsters; hemodynamics; image processing; microcirculation; oxygen microelectrode; oxygen tension; oxygen transport; oxyhemoglobin; striated muscles; vasoactive agent; video microscopy

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.

该项目的总体目标是提供所需的重要信息 为了制定一个新的概念框架来理解 向组织提供氧气的机制。目前的概念是 对Krogh的单一模型的简单模型进行了本质上的细微修改 提供特定圆柱体组织(25)的毛细管。而他的模特 提供了一个有用的开端，氧气供应的几个重要方面 都被忽视了。我们最近观察到的相当大的氧气交换 在微血管(14，45)中的分布与克罗的 毛细血管是氧气供应的唯一来源。此外，虽然 血液和组织之间的氧气压力梯度对于 氧转移，它可能不是唯一的因素导致 组织有足够的氧气。因此，改变变得势在必行 我们的概念框架。我们必须进一步调查众多的复杂情况 在广泛的制度下负责维持氧气供应的机制 条件的范围。 两个假设将在这个项目中得到检验。首先是氧气 含量是氧交换的重要调节因素。 与需求相比，氧气供应严重受限。第二个就是 一种在广泛的环境下维持组织供氧的机制 条件的范围，是由一种变化的局部化扩散 氧气转移。 实验将在仓鼠颊囊牵拉肌中进行。 我们将利用氧合血红蛋白解离曲线的左移。 (通过长期、短期服用氰酸钠来实现) 改变氧气张力和含氧量之间的关系。这 全身性低氧与血红蛋白氧亲和力的变化 等容血液稀释将提供广泛的氧气供应 使我们能够具体解决我们的假设的条件。数据在 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使用 活体视频显微镜和计算机辅助图像分析技术。在……里面 与毛细数据相结合，提供关于 毛细血管前和毛细血管后网络中的氧合作用将使用 荧光标记红细胞和PO2微电极的定位 或在小动脉壁上或在一级小动脉内 和小静脉，这取决于要解决的具体目标。这些研究 将提供有关各种相互作用机制的重要信息 负责为广泛的组织提供充足的氧气 供氧条件的光谱。我们对这些的理解 机制不仅将为我们提供更好的概念图景 组织氧合，但有助于我们理解这些因素 外周血氧利用频繁受损的原因 临床上遇到的。