GEOMETRICAL MICROSTRUCTURE AND FUNCTION IN DIAPHRAGM

横膈膜是吸气的主要肌肉。呼吸 疾病的程度，解释和身体损害是相关的，在 部分，隔膜功能的变化。治疗慢性呼吸 疾病例如，我们有责任更好地理解 健康的横膈膜功能以及这种正常功能的方式 受到疾病状态的影响。 隔膜结构和功能之间的相互关系是在 许多方面不太了解。例如，肌节的知识 急性呼吸运动中肌节长度和变化 和慢性疾病（例如，肺气肿，纤维化）可以提供深入了解 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，几乎没有测量 肌节长度在原位隔膜。拟议的调查 将检验横膈膜在一个“夜晚”运作的假设- 肌节长度的“移位”范围， 为了基本上削弱张力的发展（即，<2.3微米） 即使在总肺容量（TLC）下也能达到。1例微循环 在低于TLC的肺体积下的这种行为的结果（即，隔膜 肌节长度>2.3微米）的原因是血管将被拉伸， 直径减小，因此它们的流动动力学和O2输送 能力受损。与之竞争的假说是肌节长度 在高肺容量时变得足够短， 张力的发展，但在低肺容量的微血管将不会 被拉伸。慢性肺部疾病，即，预计会出现纤维化、肺气肿 为了改变隔膜毛细管到纤维几何形状的特定方面， 关系。例如，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 无论是微血管流量还是毛细血管长度或体积， 期待改变。 然而，纤维内扩散距离将 纤维肥大引起的增加。 这些调查将适用于 最近发展的形态测量技术和新的生理 方法（即，微血管氧分压磷光测定法 淬火，活体显微镜），以确定急性和慢性结构 隔膜毛细管和纤维几何形状的变化，并测试 这些变化对微血管流量和PO 2的影响， 需要对PO 2进行建模。 这些调查的最终目标是提供重要的新信息， 信息，以促进更好地了解相互关系 膈肌纤维几何形状与肌肉和微血管功能之间的关系 在健康和疾病的条件下。这种知识是我们固有的 理解横膈膜和意志的结构-功能关系 能够改善慢性呼吸道疾病患者的治疗。

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.