Engineering Approach to the Ventilatory Pump

描述(申请人提供)：呼吸衰竭是慢性阻塞性肺疾病(COPD)患者发病和死亡的主要原因。然而，呼吸泵功能的机械决定因素仍然不是很清楚。我们的目标是用工程学的方法来研究导致COPD泵故障的机械因素。肺部过度充气和极大的横隔膜缩短会扭曲横隔膜，导致其膜曲率丧失，并降低其肌力。这将严重限制通气泵的功能。我们的目的是建立一个通用的横隔膜力学模型，用于评估肺减容手术对重度肺气肿患者呼吸泵功能的影响。我们将扩展我们在狗的横隔膜和胸壁力学方面的知识，并将开始应用相同的原理和方法来研究正常人和严重肺气肿患者在肺减容手术(LVRS)前后的呼吸力学。最后，我们将开发一个全面的横隔膜力学理论，最终可以用来预测横隔肌在健康和疾病状态下的功能。我们将通过对狗和人类的横隔膜力学的活体研究来实现这一目标，并辅之以数学建模技术。我们的具体目标是：具体目标1：确定肺过度充气如何改变双侧半膈肌同时次最大和次最大激活时的横隔膜的压力产生能力。假设1：在高频刺激和低肺容量的情况下，双侧横隔肌的极度收缩会导致横隔膜的扁平和扭曲，因此其产生压力的能力严重受损。具体目标2：建立一个完整的横隔膜力学模型。假设3：利用隔膜的结构和本构关系的隔膜的综合力学模型应该为评估通气泵的压力产生能力提供足够的定量信息。具体目的#3：评估终末期肺气肿患者肺减容术前后和正常人的横隔膜功能。假说2a：在正常人中，肌纤维沿最大主曲率方向排列，假说2b：在严重肺气肿患者，横隔肌相对平坦，在LVRS后，横隔肌纤维曲率增加。因此，膜张力比手术前更有效地传递到跨膈压中。一旦我们得到了主曲率的分布，我们将使用我们在目标2中开发的横隔膜力学模型来预测正常人和重度肺气肿患者在LVRS前后的横隔膜功能。这些目标的完成将大大增强我们对呼吸泵在健康和疾病中的作用的基本了解。

DESCRIPTION (provided by applicant): Respiratory failure is a major cause of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). However, the mechanical determinants of ventilatory pump function are still not well understood. Our goal is to use an engineering approach to investigate the mechanical factors that mediate pump failure in COPD. Hyperinflation of the lungs and extreme diaphragm shortening can distort the sheet of the diaphragm, cause loss of its membrane curvature, and reduce its muscle force. This will severely limit the function of the ventilatory pump. Our objective is to build a general model of diaphragm mechanics that can be utilized to evaluate the effect of lung volume reduction surgery on respiratory pump function in patients with severe emphysema. We will extend our knowledge of diaphragm and chest wall mechanics in dogs, and will begin to apply the same principles and approaches to the study of ventilatory mechanics in normal human subjects and patients with severe emphysema before and after lung volume reduction surgery (LVRS). Finally, we will develop a comprehensive theory of diaphragm mechanics that can eventually be used to predict diaphragm muscle function in both healthy and diseased states. We will achieve this objective with in vivo studies of diaphragm mechanics in dogs and humans complemented with mathematical modeling techniques. Our specific aims are: Specific Aim #1: To determine how hyperinflation of the lungs alters the pressure generating ability of the diaphragm during simultaneous sub-maximal and maximal activation of both hemi-diaphragms. Hypothesis 1: Extreme muscle contraction of both hemi-diaphragms at high frequencies of stimulation and at lower lung volumes causes flattening and distortion of the membrane of the diaphragm, and therefore its generating ability of pressure is severely compromised. Specific Aim #2: To develop a comprehensive mechanical model of the diaphragm. Hypothesis 3: A comprehensive mechanical model of the diaphragm that utilizes both structure and constitutive relationships of the diaphragm should provide sufficient quantitative information on the evaluation of the pressure generating ability of the ventilatory pump. Specific Aim #3: To evaluate diaphragm function in patients with end-stage emphysema before and after LVRS, and in normal humans. Hypothesis 2a: In normal individuals, muscle fibers are oriented along the direction of maximum principal curvature, Hypothesis 2b: In severe emphysema patients, the diaphragm is comparatively flattened, and after LVRS, there is a gain in diaphragm muscle fiber curvature. Therefore, membrane tension is transmitted into trans-diaphragmatic pressure more effectively than before the surgery. Once we obtained the distribution of principal curvatures we will use our model of diaphragm mechanics developed in Aim 2 to predict diaphragm function in normal individuals and patients with severe emphysema before and after LVRS. The completion of these aims will significantly enhance our fundamental understanding of the ventilatory pump function in health and disease.