GEOMETRICAL MICROSTRUCTURE AND FUNCTION IN DIAPHRAGM

横隔膜是灵感的主要肌肉。在呼吸中 疾病，呼吸和身体损害的程度是相关的， 部分，对隔膜功能的改变。慢性呼吸系统疾病的治疗 疾病，如肺气肿，取决于我们更好地理解 横隔膜的健康功能和这种正常功能的方式 会受到疾病状态的影响。 隔膜结构和功能之间的相互关系如下所示 许多方面人们对此知之甚少。例如，肌节的知识 急性呼吸动作时肌节长度及其变化 慢性疾病(如肺气肿、纤维化)可以提供对 肌肉收缩功能、能量需求、区域间和区域内 纤维变形、微血管功能和氧交换电位 毛细管床。然而，到目前为止，几乎还没有测量到 肌节长度在原位横隔膜。拟议的调查 将检验横隔膜在一个“夜晚”运行的假设 移位的肌节长度范围，使得长度足够短 实质上损害张力发展(即2.3微米)不是 即使在总肺活量(TLC)的情况下也是如此。一种微循环 这一行为在TLC(即横隔膜)以下的肺体积上的后果 肌节长度2.3微米)是血管会被拉伸，他们的 直径减小，因此它们的流动动力学和氧气输送 能力受损。相互竞争的假说是肌节长度将 在高肺容量时变得足够短，可能会限制 张力发展，但在低肺容量时微血管不会 被拉长了。预计会出现慢性肺部疾病，如纤维化、肺气肿 要改变隔膜毛细到光纤的几何形状 两性关系。例如，纤维化中肺体积的减少将 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……里面 肺气肿，无论是微血管血流还是毛细血管长度或体积都不会 被期待着改变。但是，光纤内扩散距离将 因纤维肥大而增加。这些调查将适用于 最新发展的形态测量技术和新的生理学 方法(即用磷光法测定微血管血氧分压 猝灭，活体显微镜)以识别急性和慢性结构 横隔膜毛细血管和纤维几何形态的变化及测试 这些变化对微血管流量和氧分压的影响也提供了数据 为PO2建模所必需的。 这些调查的最终目标是提供重要的新的 有助于更好地了解相互关系的信息 横隔肌纤维形态与肌肉和微血管功能之间的关系 在健康和疾病的条件下。这种知识是我们的固有知识 对隔膜结构-功能关系和意志的理解 改善慢性呼吸系统疾病患者的治疗。

The diaphragm is the principal muscle of inspiration. In respiratory disease, the degree of ventilatory and physical impairment is related, in part, to changes of diaphragm function. Treatment of chronic respiratory diseases e.g., emphysema is incumbent on our ability to better understand diaphragm function in health and the manner in which this normal function is impacted by the disease state. The interrelationships between diaphragm structure and function are in many respects poorly understood. For example, knowledge of sarcomere length and changes in sarcomere length during acute respiratory maneuvers and chronic diseases (e.g., emphysema, fibrosis) can provide insights into muscle contractile function, energetic demands, inter- and intra-regional fiber deformation, microvascular function and O2 exchange potential of the capillary bed. To date, however, there are almost no measurements of sarcomere length in the in situ diaphragm. The proposed investigations will test the hypothesis that the diaphragm operates over a "night- shifted" range of sarcomere lengths such that lengths sufficiently short to substantially impair tension development (i.e., <2.3 microns) are not attained, even at total lung capacity (TLC). One microcirculatory consequence of this behavior at lung volumes below TLC (i.e., diaphragm sarcomere length >2.3 microns) is that vessels will be stretched, their diameter decreased and consequently their flow dynamics and O2 delivery capacity impaired. The competing hypothesis is that sarcomere length will become sufficiently short at high lung volumes to potentially limit tension development, but at low lung volumes the microvasculature will not be stretched. Chronic lung diseases i.e., fibrosis, emphysema are expected to change specific aspects of diaphragm capillary-to-fiber geometrical relationships. For instance, the reduced lung volumes in fibrosis will increase sarcomere length and stretch the capillary bed thereby impairing flow, increasing flow heterogeneity and reducing O2 delivery. In emphysema, neither microvascular flow nor capillary length or volume would be expected to change. However, intrafiber diffusion distances will increase consequent to fiber hypertrophy. These investigations will apply recently developed morphometric techniques and novel physiologic approaches (i.e., microvascular PO2 determination by phosphorescence quenching, intravital microscopy) to identify acute and chronic structural changes in diaphragm capillary and fiber geometry and test the effect of these changes on microvascular flow and PO2 and also provide data necessary for modelling PO2. The ultimate goal of these investigations is to provide significant new information to facilitate a better understanding of the interrelationships between diaphragm fiber geometry and muscular and microvascular function under conditions of health and disease. This knowledge is intrinsic to our understanding of structure-function relationships in diaphragm and will enable improved treatment of patients with chronic respiratory disease.