FUNCTIONAL ASPECTS OF OXYGEN DELIVERY

供氧的功能方面

• 批准号: 6262687
• 负责人: Marcos Intaglietta
• 金额: $ 37.25万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-22 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6262687
• 关键词: arterioles; blood circulation; blood viscosity; diffusion; hamsters; hemodynamics; microcirculation; nitric oxide; oxygen consumption; oxygen tension; oxygen transport; prostaglandins; vascular endothelium; vascular endothelium permeability; vascular smooth muscle; vasomotion

Our hypothesis is that arterioles are the principal suppliers of oxygen to skeletal muscle at rest and connective tissue, and that a substantial fraction of the oxygen delivered to the tissue by the arterioles is used by the arteriolar vessel wall. High oxygen consumption by the arteriolar wall/endothelium/smooth muscle causes the presence of large oxygen gradients next to the blood tissue interface. These gradients determine the high rate of oxygen exit from arterioles by diffusion a phenomenon measured by other investigators using oxygen microelectrodes and the change in microvessel blood oxygen saturation and by us using the phosphorescence quenching technique. The rate of oxygen consumption by the arteriolar microvascular wall may account for as much as 30% of total oxygen use by some tissues, a phenomenon also found in whole organ studies by others. Our hypothesis is that arteriolar wall oxygen consumption is increased by vasoconstriction, low shear stress at the blood-endothelium interface, and decreased NO availability which lowers tissue oxygenation. Conversely the opposite effects lower oxygen consumption by the arteriolar wall and increase tissue oxygen. An additional mechanism is that NO curbs or minimizes oxygen consumption of the vessel wall and acts as a brake to oxygen consumption. It is proposed that blood viscosity is a determinant of p02 distribution in the microcirculation because: 1) Viscosity is a factor in determining peripheral vascular resistance, blood flow and perfusion; 2) The rate of oxygen exit from the microvessels is the balance between flow velocity and outward diffusion; and, 3) Blood viscosity determines the release of endothelial derived prostaglandin and NO via wall shear stress mediated mechanisms. These mechanisms directly affect functional capillary density, which is a determinant of tissue survival even though capillaries provide minimal oxygen to the tissue. The methods comprise in vivo measurements of microvascular transport properties including micro-p02 and micro-NO measurements in blood and tissue, blood flow velocity, functional capillary density and arteriolar reactivity. Our investigations use the method of mass balance to predict the vessel wall oxygen consumption needed to explain the rate of oxygen exit from the arterioles, and the high resolution phosphorescence quenching oxygen measurement technique to experimentally verify the theoretical predictions. Our research aims at advancing our understanding of tissue oxygenation and provides a new conceptual framework with which to analyze the ischemic process.

我们的假设是，小动脉是静止和结缔组织骨骼肌氧的主要供应商，并且小动脉容器壁使用了小动脉传递到组织的大部分氧气。小动脉壁/内皮/平滑肌的高氧消耗会导致血液组织界面旁边的大氧梯度的存在。这些梯度通过扩散通过使用氧气微电极测量的现象来确定从小动脉出口的高氧速率，以及微血管血液氧饱和度的变化以及使用磷光猝灭技术的变化。小动脉微血管壁的氧气消耗速率可能占某些组织总使用总氧气的30％，而其他人在整个器官研究中也发现了这一现象。我们的假设是，通过血管收缩，低剪切应力在血内皮界面上的低剪切应力增加，并且没有降低可降低组织氧合的可用性。相反，相反的影响小动脉壁降低氧气的消耗并增加组织氧。另一种机制是，没有遏制或最大程度地减少容器壁的消耗，并充当耗氧的制动器。有人提出，血液粘度是微循环中p02分布的决定因素，因为：1）粘度是确定周围血管阻力，血流和灌注的因素； 2）从微血管中退出的氧气速率是流速和向外扩散之间的平衡； 3）血液粘度决定了内皮衍生的前列腺素的释放，没有通过壁剪应力介导的机制释放。这些机制直接影响功能性毛细管密度，即使毛细血管为组织提供最小的氧气，这是组织存活的决定因素。该方法包括在体内测量微血管转运性能，包括微型P02和血液和组织中的微-NO测量，血流速度，功能性毛细管密度和小动脉反应性。我们的研究使用质量平衡方法来预测解释从小动脉出口速率的血管壁消耗，以及高分辨率磷光淬氧氧测量技术以实验验证理论预测。我们的研究旨在促进我们对组织氧合的理解，并提供一个新的概念框架，以分析缺血过程。