MUSCLE CAPILLARY GEOMETRY, FLOW, AND OXYGEN TRANSFER

描述(改编自申请人的摘要)：有效的氧气扩散 从红细胞到肌肉纤维是维持细胞生长所必需的 完整性和支持氧化功能。越来越多的证据表明 骨骼肌对氧气扩散的主要阻力是 细胞外。在各种生理和病理条件下，O2 扩散功能受损，导致肌肉疲劳/衰竭，有时 退化性变化。形态测量技术描述了 急性和慢性扰动对毛细管几何的影响。 然而，这些变化对RBC血流动力学、氧交换和 肌肉功能尚未确定。建议的目标是 调查是利用已建立的病理生理学模型 重新配置毛细管几何结构并确定它们之间关系的条件 毛细血管几何、毛细血管血流动力学、氧交换与肌肉 功能。具体地说，假设毛细血管适应 (管腔直径减小、内陷、增强拉伸)在骨骼中发现 糖尿病动物或慢性心脏病患者的肌肉 失效，将损害RBC流量并增加RBC分布 异质性，从而减少血液-组织氧交换和肌肉 性能。两块纤维类型相似但氧化程度不同的肌肉 将利用容量(棘斜方肌和横隔膜)。实验 设计的条件是强调肌肉血液流动和氧气的能力 交换(血管扩张、低氧血症/高氧血症、肌肉收缩)。本地 血管扩张将被用来区分微动脉血管调节 影响和毛细几何变化引起的影响。 微血管和肌肉功能将使用Inlive进行评估 显微镜、磷光猝灭(微血管氧分压)和肌肉张力 测量。这些研究将结合已建立的光学、 磷光和功能技术，以调查能力 毛细血管几何变化扰乱肌肉氧交换获得 关于毛细血管几何学在促进肌肉方面的作用的信息 氧气在健康和一系列常见疾病状态下的传递。

DESCRIPTION (Adapted from the applicant's abstract): Effective O2 diffusion from the red blood cell to the muscle fiber is necessary to sustain cellular integrity and support oxidative function. There is increasing evidence that the principal resistance to O2 diffusion in skeletal muscle is extracellular. Under various physiological and pathological conditions, O2 diffusion is impaired resulting in muscle fatigue/failure and sometimes degenerative changes. Morphometric techniques have described the consequences of acute and chronic perturbations on capillary geometry. However, the effects of these changes on RBC hemodynamics, O2 exchange and muscle function have not been determined. The objective of the proposed investigations is to utilize established models of pathophysiological conditions to reconfigure capillary geometry and determine the relationships between capillary geometry, capillary hemodynamics, O2 exchange and muscle function. Specifically, it is hypothesized that capillary adaptations (reduced luminal diameter, involution, enhanced stretch) found in skeletal muscle of animals with diabetes, or those suffering from chronic heart failure, will act to impair RBC flux and augment RBC distribution heterogeneity thereby reducing blood-tissue O2 exchange and muscle performance. Two muscles of similar fiber type but differing in oxidative capacity (spinotrapezius and diaphragm) will be utilized. Experimental conditions are designed to stress the capacity for muscle blood flow and O2 exchange (vasodilation, hypoxemia/hyperoxemia, muscle contractions). Local vasodilation will be used to distinguish between arteriolar vasoregulatory effects and those arising from capillary geometrical alterations. Microvascular and muscle function will be assessed using intravital microscopy, phosphorescence quenching (microvascular PO2) and muscle tension measurements. These studies will combine established optical, phosphorescence and functional technologies to investigate the capacity for capillary geometrical changes to perturb muscle O2 exchange to obtain information regarding the role of capillary geometry in facilitating muscle O2 delivery in health and a series of common disease states.