MECHANISMS OF RESPIRATORY MUSCLE ADAPTATION TO LOAD

申请者的长期目标是在儿科领域追求学术生涯 胸科药物。申请者计划发展呼吸系统方面的专业知识 肌肉功能，特别强调基本的生化代谢 和结构机制，负责适应 呼吸肌增加了工作负荷。使用呼吸系统模型 慢性仪器化非麻醉绵羊的肌肉疲劳 提案涉及基本机制，并将侧重于研究) 横隔膜中神经与机械的相互作用，b)衬底 (碳水化合物和脂类)可利用性和利用率及其关系 起作用，c)扰动的影响，如呼吸增加 负荷和慢性低氧对a)和b)以上，以及d)结构的关系 与呼吸肌的早期成熟有关 生活。使用最先进的技术，生理指标(PDI， 将测量隔膜肌电、通气量和动脉血气) 在吸气和呼气时阻力负荷呼吸。这个 由膜片(应变片传感器)产生的力将与 至隔膜的工作长度(声学测微仪、电感线圈) 和PDI。利用组织化学、形态计量学和生化技术， 横隔膜利用葡萄糖、游离脂肪酸和肌内 糖原和甘油三酯将被测定(膈静脉插管， 菲克原理)，负责利用它们的酶将是 学习。氧气消耗和流向隔膜的血液(微球 方法)将被测量。在下列情况下，将检查隔膜的耐久性 肋间肌肉失神经，当迷走神经被阻断时 (迷走神经干降温或局部麻醉)。横隔膜的耐力和耐力 它的结构和生化性质将在暴露于 慢性缺氧。此外，为了更好地了解糖尿病的易感性 对于呼吸肌疲劳的年轻人，这些研究将在 小羊羔。对结构、生化和生理的理解 急性和慢性应激相关呼吸肌的变化 可能会产生新的概念来预防和治疗 呼吸肌疲劳和呼吸衰竭。

The applicant's long-term goal is to pursue an academic career in pediatric chest medicine. The applicant plans to develop expertise in respiratory muscle function with special emphasis on the basic biochemical metabolic and structural mechanisms which are responsible for the adaptation of the respiratory muscles to increased work load. Using a model of respiratory muscle fatigue in chronically instrumented unanesthetized sheep, this proposal addresses basic mechanisms and will focus on the study of a) neural to mechanical interaction in the diaphragm, b) substrate (carbohydrates and lipids) availability and utilization and their relation to function, c) the effects of perturbations such as increased respiratory load and chronic hypoxia on a) & b) above, and d) the relation of structure to function with respect to maturation of respiratory muscles in early life. Using state of the art techniques, physiologic indices (Pdi, diaphragm EMG, ventilation and arterial blood gases) will be measured during inspiratory and expiratory flow resistive loaded breathing. The force generated by the diaphragm (strain gauge transducers) will be related to the operating length of the diaphragm (sonomicrometry, inductance coils) and to Pdi. Using histochemical, morphometric and biochemical techniques, diaphragmatic utilization of glucose, free fatty acids, and intramuscular glycogen and triglyceride will be determined (phrenic vein catheterization, Fick principle) and the enzymes responsible for their utilization will be studied. Oxygen consumption and blood flow to the diaphragm (microsphere method) will be measured. Endurance of the diaphragm will be examined when the intercostal muscles are denervated and when the vagus nerve is blocked (vagal trunk cooling or local anesthesia). Endurance of the diaphragm and its structural and biochemical properties will be studied after exposure to chronic hypoxia. In addition, to better understand the susceptibility of the young to respiratory muscle fatigue, these studies will be performed in the young lamb. Understanding the structural, biochemical and physiologic changes in the respiratory muscles associated with acute and chronic stress is likely to generate new concepts for the prevention and treatment of respiratory muscle fatigue and respiratory failure.