DIAPHRAGM MICROGEOMETRY AND FUNCTION--IMPACT OF DISEASE

在呼吸系统疾病中，呼吸和身体损害的程度 部分与横膈膜功能有关。 治疗慢性 呼吸道疾病例如，肺气肿取决于对 健康的横膈膜功能以及这种正常功能如何受到 疾病状态。 膈肌结构与微循环的相互关系 功能尚未研究。 对急性心肌梗死患者肌节长度的认识 呼吸操作和慢性疾病（例如，肺气肿、纤维化） 提供对肌肉收缩功能，能量需求， 局部纤维变形、微血管功能和氧交换 毛细管床的潜力。 然而，几乎没有测量 的肌节长度。 调查将 检验横膈膜在“右移”上工作的假设 肌节长度的范围，使得长度足够短， 基本上损害张力发展（即，出租人2.3微米）， 即使在总肺容量（TLC）下也能达到。 因此，在肺容量低于 TLC（i.e.，膈肌肌节长度大于2.3微米）血管 会被拉伸，它们的直径减小，动力学和O2 交付能力受损。 另一种假说是肌节 在高肺容量下长度将变得足够短 限制张力的发展，但在体积较小的TLC微血管 不会被拉伸。 慢性疾病，即，纤维化、肺气肿和 低氧血症预期改变隔膜毛细血管的特定方面， 纤维几何关系 纤维化中肺体积的减少将 增加肌节长度并拉伸毛细血管床， 流量，增加流量异质性和减少O2输送。 在肺气肿中， 无论是微血管流量还是毛细血管表面积， 变化 然而，纤维内扩散距离将由于纤维 肥厚 最近开发的形态测量技术和新的 生理方法（即，微血管PO2测定 磷光猝灭，隔膜活体显微镜）将被 用于识别膈肌毛细血管的急性和慢性变化， 纤维几何形状，并测试它们对微血管流量和PO2的影响， 为模拟O2交换和PO2提供必要的数据。 这些调查的最终目标是提供一个更好的 了解隔膜纤维几何形状之间的相互关系 以及肌肉和微血管的功能。

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.