FUNCTIONAL ASPECTS OF OXYGEN DELIVERY

我们的假设是，小动脉是静息状态下骨骼肌和结缔组织的主要氧气供应者，小动脉输送到组织中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气梯度。这些梯度决定了小动脉氧气通过扩散排出的高速率，这是其他研究人员使用氧气微电极和我们使用磷光猝灭技术测量的微血管血氧饱和度变化所测量到的现象。微动脉微血管壁的耗氧率可能占某些组织总耗氧量的30%，其他人在整个器官的研究中也发现了这一现象。我们的假设是，动脉壁耗氧量因血管收缩、血液-内皮界面的低剪应力而增加，并减少了NO的供应，从而降低了组织的氧合。相反，相反的作用降低了小动脉壁的耗氧量，增加了组织的氧气。另一种机制是NO抑制或最小化血管壁的氧气消耗，并对氧气消耗起到刹车的作用。认为血液粘度是P02在微循环中分布的决定因素，因为：1)粘度是决定外周血管阻力、血流和灌注量的一个因素；2)从微血管中排出氧气的速率是流速和向外扩散之间的平衡；3)血液粘度通过壁切应力调节机制决定内皮源性前列腺素和一氧化氮的释放。这些机制直接影响功能性毛细血管密度，这是组织存活的一个决定因素，即使毛细血管为组织提供最低限度的氧气。这些方法包括对微血管传输特性的活体测量，包括血液和组织中微量P02和微量NO的测量、血流速度、功能毛细血管密度和微动脉反应性。我们的研究使用质量平衡法预测了解释小动脉出氧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对理论预测进行了实验验证。我们的研究旨在促进我们对组织氧合的理解，并为分析缺血过程提供一个新的概念框架。

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.