DIAPHRAGM MICROGEOMETRY AND FUNCTION--IMPACT OF DISEASE

在呼吸系统疾病中，指呼吸和身体损害的程度 部分与横隔膜的功能有关。慢性阻塞性肺疾病的治疗 呼吸系统疾病，如肺气肿，依赖于理解 健康状态下的横隔膜功能及其对正常功能的影响 疾病状态。 横隔膜结构与微循环的相互关系 其功能尚未得到研究。对急性加重期肌节长度的认识 呼吸动作和慢性病(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，几乎没有测量结果 在原位横隔膜的肌节长度。我们的调查将 测试横隔膜在“右移”状态下运行的假设 肌节长度的范围足够短到 实质上损害张力发展(即，较小的2.3微米)不 即使在总肺活量(TLC)的情况下也是如此。因此，在肺体积低于 薄层(隔膜肌节长度大于2.3微米)血管 会被拉伸，它们的直径会变小，动力学和氧气会变慢 运送能力受损。相互竞争的假说是，肌节 当肺容量较大时，长度将变得足够短，从而可能 限制张力的发展，但在体积较小的TLC微血管 不会被拉长。慢性疾病，如纤维化、肺气肿和 低氧血症预计会改变隔膜毛细血管的特定方面 纤维几何关系。纤维化时肺体积的减少将 增加肌节长度和拉伸毛细血管床，从而损害 流动，增加流动的不均一性，减少氧气的输送。在肺气肿中， 无论是微血管流动还是毛细血管表面积都不会 变化。然而，由于光纤的存在，光纤内的扩散距离将会增加 肥大。最近发展起来的形态测量技术和新颖的 生理学方法(即，通过以下方法测定微血管PO2 磷光猝灭，隔膜活体显微镜)将 用来识别隔膜毛细血管的急性和慢性变化 纤维的几何构型及其对微血管流量和氧分压的影响 提供模拟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 对横隔膜纤维几何形状之间相互关系的理解 以及健康和疾病中的肌肉和微血管功能。

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.