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，小动脉是静止时骨骼肌和结缔组织的主要氧气供应者，并且小动脉输送到组织的氧气的很大一部分被小动脉血管壁使用。小动脉壁/内皮/平滑肌的高耗氧量导致血液组织界面附近存在大的氧梯度。这些梯度决定了通过扩散从小动脉排出氧气的高速率，这是其他研究人员使用氧微电极和微血管血氧饱和度的变化以及我们使用磷光猝灭技术测量的现象。小动脉微血管壁的耗氧率可能占某些组织总耗氧量的 30%，其他人在整个器官研究中也发现了这种现象。我们的假设是，血管收缩、血液-内皮界面的低剪切应力以及一氧化氮可用性降低（从而降低组织氧合作用）会增加小动脉壁耗氧量。相反，相反的作用会降低小动脉壁的耗氧量并增加组织的氧气。另一个机制是 NO 抑制或最小化血管壁的氧气消耗，并充当氧气消耗的制动器。有人提出，血液粘度是微循环中 pO2 分布的决定因素，因为： 1) 粘度是决定外周血管阻力、血流量和灌注的因素； 2）氧气从微血管排出的速率是流速与向外扩散之间的平衡； 3) 血液粘度通过壁剪切应力介导的机制决定内皮衍生的前列腺素和 NO 的释放。这些机制直接影响功能性毛细血管密度，这是组织存活的决定因素，即使毛细血管为组织提供了最少的氧气。该方法包括微血管输送特性的体内测量，包括血液和组织中的微pO2和微NO测量、血流速度、功能性毛细血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小动脉氧气排出速率所需的血管壁耗氧量，并使用高分辨率磷光猝灭氧测量技术来通过实验验证理论预测。我们的研究旨在增进我们对组织氧合的理解，并提供一个新的概念框架来分析缺血过程。