MUSCLE CAPILLARY GEOMETRY, FLOW, AND OXYGEN TRANSFER

描述（改编自申请人摘要）：有效的O2扩散 从红细胞到肌肉纤维是维持细胞 完整性和支持氧化功能。 越来越多的证据表明 骨骼肌中氧气扩散主要阻力是 细胞外的 在各种生理和病理条件下，O2 扩散受损，导致肌肉疲劳/衰竭，有时 退化性变化 形态测量技术已经描述了 急性和慢性扰动对毛细血管几何形状的影响。 然而，这些变化对红细胞血流动力学、O2交换和 肌肉功能尚未确定。 建议的目标 研究的目的是利用已建立的病理生理学模型 重新配置毛细管几何形状并确定关系的条件 毛细血管几何形状、毛细血管血液动力学、O2交换和肌肉之间 功能 具体来说，假设毛细血管适应性 （管腔直径减小、退化、拉伸增强） 患有糖尿病或患有慢性心脏病的动物的肌肉 失败，将损害红细胞流量和增加红细胞分布 异质性，从而减少血液组织O2交换和肌肉 性能 两块肌肉的纤维类型相似，但氧化能力不同 将利用容量（脊髓和隔膜）。 实验 条件被设计成强调肌肉血流量和O2的能力 交换（血管舒张、低氧血症/高氧血症、肌肉收缩）。 当地 血管舒张将用于区分小动脉血管调节性 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活体评估 显微镜、磷光淬灭（微血管PO 2）和肌肉张力 测量. 这些研究将结合联合收割机建立的光学， 磷光和功能技术，以调查的能力， 毛细血管几何变化，以干扰肌肉O2交换， 关于毛细血管几何形状在促进肌肉中的作用的信息 健康和一系列常见疾病状态下的O2输送。

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.