MIDDLE EAR PRESSURE REGULATION IN HEALTH AND DISEASE

中耳(ME)压力调节要求咽鼓管(ET)开口提供足够数量的气体，以平衡通过粘膜与血液进行气体交换所造成的净损失。调节失调导致ME低压、粘膜炎症和渗出性中耳炎(OME)。平衡供需关系的破坏可能是由于ET扩张期间交换的气体数量减少，或跨粘膜气体交换速度增加，或两者兼而有之。了解控制压力调节的机制和破坏正常功能的条件是制定OME预防或治疗策略的基本原理。我们最近的研究为疾病发病机制的水肿性空泡学说提供了令人信服的支持，也表明ET功能可以在ME病理的前提条件下上调。估计了恒河猴ME压力调节数学模型的自由参数。使用这些估计，我们的模型准确地预测了测量的ME气体成分、MEE压力响应对各种条件的动力学以及实验和临床观察的反直觉结果。其他实验表明，惰性气体的跨粘膜交换主要受灌流限制，而与血液成分化学结合的气体主要受扩散限制。这些结果的必然结果是炎症和/或更快的血流速度增加了氮气和其他惰性气体的跨粘膜交换。该模型将持续性OME描述为一种粘膜疾病，规定了人为使ME充气的操作可以促进疾病缓解的条件。拟议中的实验改进了我们的数学模型，以便更好地代表生理学，澄清正常ME生理学的某些方面(例如，乳突气细胞在压力调节中的作用)，进一步定义炎症和渗出对跨粘膜气体交换速率的影响，评估特定治疗方法对跨粘膜气体交换RTE的影响，完成治疗方法对跨粘膜气体交换速率的影响的开发和测试，完成评估粘膜健康的仪器的开发和测试，并为人体受试者生成各种模型参数的初步估计。这些结果将被用来。1)提高我们对ME压力调节在健康和疾病中的认识，2)发展ME压力调节失调的诊断试验，3)提出合理的干预措施来呈现或治疗OME。

Middle ear (ME) pressure regulation requires that Eustachian tube (ET) openings supply sufficient quantities of gases to balance the net loss due to transmucosal gas exchange with blood. Dysregulation causes ME under- pressures, mucosal inflammation and otitis media with effusion (OME). Disruption of the balance supply-demand relationship can result from a decreased volume of gas exchanged during ET dilations, an increased rate of transmucosal gas exchange, or both A knowledge of the mechanisms that control pressure regulation and of the conditions that disrupt normal function is fundamental to developing rationale preention or treatment strategies for OME. Recent studies conducted by us provided convincing support for the hydrops ex vacuo theory of disease pathogenesis and also showed that ET function can be up-regulated by preconditions to ME pathology. Free parameters of a mathematical model of ME pressure regulation were estimated in the monkey. Using those estimates, our model accurately predicted the measured ME gas composition, the kinetics of the MEE pressure response to a variety of conditions, and the counter-intuitive results of experiments and clinical observations. Other experiments showed that transmucosal exchange of inert gases is primarily perfusion limited, while that of gases that chemically bind with blood components is primarily diffusion limited. A corollary to these results is an increased transmucosal exchange of N2 and other inert gases by inflammation and/or greater blood flow rates. Representing persistent OME as a mucosal disease, the model prescribes the conditions under which maneuvers that artificially aerate the ME can promote disease resolution. The proposed experiments refine our mathematical model so as to better represent physiology, clarify certain aspects of normal ME physiology (e.g. role of mastoid air cells in pressure regulation), further define the effects of inflammation and effusion on the rate of transmucosal gas exchange, evaluate specific treatments for their effect on the rte of transmucosal gas exchange, complete the development and testing of treatments for their effect on the rate of transmucosal gas exchange, complete the development and testing of instruments that assess mucosal health, and generate initial estimates of the various model parameters for human subjects. These results will be used to. 1) improve our understanding of ME pressure regulation in health and disease, 2) develop diagnostic tests of ME pressure dysregulation, and 3) suggest rational interventions to present or treat OME.