DIAPHRAGM MICROGEOMETRY AND FUNCTION--IMPACT OF DISEASE

隔膜微观几何形状和功能——疾病的影响

• 批准号: 5213189
• 负责人: DAVID C POOLE
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5213189
• 关键词: blood flow measurement; capillary; diaphragm; dogs; emphysema; hamsters; laboratory rat; lung ischemia /hypoxia; microcirculation; oxygen transport; pulmonary circulation; pulmonary fibrosis /granuloma; respiratory airway volume; respiratory function; respiratory gas; sarcomeres; video microscopy

In respiratory disease, the degree of ventilatory and physical impairment is related, in part to diaphragm function. Treatment of chronic respiratory diseases e.g., emphysema is dependent on understanding diaphragm function in health and how this normal function is impacted by the disease state. Interrelationships between diaphragm structure and microcirculatory function have not been studies. Knowledge of sarcomere length during acute respiratory maneuvers and chronic diseases (e.g., emphysema, fibrosis) provide insights into muscle contractile function, energetic demands, regional fiber deformation, microvascular function and O2 exchange potential of the capillary bed. However, there are almost no measurements of sarcomere length in the in situ diaphragm. Thee investigations will test the hypothesis that the diaphragm operates over a "right-shifted" range of sarcomere lengths such that lengths sufficiently short to substantially impair tension development (i.e., lessor 2.3 microns) are not attained, even at total lung capacity (TLC). Thus, at lung volumes below TLC (i.el, diaphragm sarcomere length greater than 2.3 microns) vessels will be stretched, their diameter decreased and slow dynamics and O2 delivery capacity impaired. The competing hypothesis is that sarcomere length will become sufficiently short at a high lung volumes to potentially limit tension development, but at volumes lessor TLC the microvasculature will not be stretched. Chronic diseases i.e., fibrosis, emphysema and hypoxemia are expected to change specific aspects of diaphragm capillary to fiber geometrical relationships. Reduced lung volumes in fibrosis will increase sarcomere length and stretch the capillary bed thereby impairing flow, increasing flow heterogeneity and reducing O2 deliver. In emphysema, neither microvascular flow nor capillary surface area would be expected to change. However, intrafiber diffusion distances will increase due to fiber hypertrophy. Recently developed morphometric techniques and novel physiologic approaches (i.e., microvascular PO2 determination by phosphorescence quenching, diaphragm intravital microscopy) will be employed to identify acute and chronic change in diaphragm capillary and fiber geometry and test their effect on microvascular flow and PO2 and also provide data necessary for modelling O2 exchange and PO2. The ultimate goal of these investigations is to provide a better understanding of the interrelationships between diaphragm fiber geometry and muscular and microvascular function in health and disease.

在呼吸道疾病中，通气和身体障碍的程度 与隔膜功能有关。 慢性治疗 呼吸道疾病，例如，肺气肿取决于理解 隔膜在健康方面的功能以及这种正常功能如何受到 疾病状态。 隔膜结构与微循环之间的相互关系 功能还没有研究。 急性期间的肌节长度的知识 呼吸道疾病和慢性疾病（例如肺气肿，纤维化） 提供有关肌肉收缩功能，充满活力的需求的见解， 区域纤维变形，微血管功能和O2交换 毛细管床的潜力。 但是，几乎没有测量 原位隔膜中的肌节长度。 您的调查会 测试隔膜在“右移”上运行的假设 肌节长度的范围使得长度足够短 大大损害了张力的发展（即出租人2.3微米）不是 即使以总肺容量（TLC）也达到。 因此，在下面的肺部体积 TLC（i.el，隔膜肌节长度大于2.3微米）容器 将拉伸，直径降低并缓慢动力学和O2 交货能力受损。 竞争的假设是肌节 长度将在高肺体积上变得足够短，可能 限制张力的发展，但在出租人TLC时限制了微脉管系统 不会拉伸。 慢性疾病，即纤维化，肺气肿和 预计低氧血症将改变diaphragm毛细管的特定方面 纤维几何关系。 减少纤维化中的肺体积将 增加肌节的长度并拉伸毛细管床，从而损害 流量，流量异质性增加并减少O2传递。 在肺气肿中， 微血管流或毛细血管表面积既不会预期 改变。 但是，由于纤维，纤维内扩散距离将增加 肥大。 最近开发了形态计量技术和新颖 生理方法（即微血管PO2确定 磷光猝灭，隔膜浸润显微镜将是 用于确定diaphragm毛细管的急性和慢性变化 纤维几何形状并测试其对微血管流和PO2的影响，还测试 提供建模O2交换和PO2所需的数据。 这些调查的最终目标是提供更好的 了解膜片纤维几何形状之间的相互关系 以及健康和疾病中的肌肉和微血管功能。