Gas Supply, Demand and Middle Ear Gas Balance

气体供应、需求和中耳气体平衡

• 批准号: 7657382
• 负责人: Cuneyt Metin Alper
• 金额: $ 10.43万
• 依托单位: CHILDREN'S HOSP PITTSBURGH/UPMC HLTH SYS
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7657382
• 关键词: Adolescent; Adult; Affect; Air; Animal Experiments; Appendix; Behavior; Blood; Bolus Infusion; Buffers; Chemicals; Child; Cicatrix; Clinical; Communicable Diseases; Condition; Constitutional; Constriction procedure; Controlled Environment; Data; Data Set; Databases; Diagnosis; Diffusion; Disease; Disease model; ET protocol; Ear; Edema; Enrollment; Equilibrium; Eustachian Tube; Evolution; Failure; Feedback; Functional disorder; Funding; Gases; Genetic Predisposition to Disease; Goals; Human; In Situ; Individual; Infection; Inflammation; Inflammatory; Knowledge; Laboratories; Link; Liquid substance; Logistic Regressions; Mastoid process; Measurable; Measurement; Measures; Mechanics; Mediating; Melanocytic nevus; Methods; Modeling; Modification; Mole the mammal; Monkeys; Mucous Membrane; Muscle; Nasopharynx; Neurogenic Inflammation; Noble Gases; Nose; Otitis Media; Otitis Media with Effusion; Otoscopy; Partial Pressure; Pathogenesis; Pathology; Pathway interactions; Peripheral; Physical Function; Physiological; Population; Principal Investigator; Process; Property; Protocols documentation; Publishing; Rate; Recording of previous events; Recurrence; Regulation; Relative (related person); Research; Research Personnel; Research Project Grants; Resistance; Rhinovirus; Risk; Role; Secondary to; Series; Simulate; Standards of Weights and Measures; Sum; System; Temperature; Test Result; Testing; Time; Tissues; Translational Research; Tube; Tympanic membrane; Tympanometry; Upper Respiratory Infections; Viral; Work; concept; day; effusion; human data; insight; interest; middle ear; novel; outcome forecast; physical model; physical property; practical application; pressure; prevent; prognostic; programs; psychologic; research study; response; social; theories; vector; virus genetics; volunteer

GAS SUPPLY, DEMAND AND MIDDLE EAR GAS BALANCE From the results of studies in monkeys, we developed a multi-level, interactive, feedback model to describe the efficiency of middle ear (ME) pressure-regulation and the pathophysiological consequences of disregulation. That model requires knowledge only of system geometry and the physiochemical properties of represented gases and tissues to predict the behavior of ME pressure and the conditions that favor transitions between normal and pathological states. If valid, the model allows for testing previously suggested mechanisms of ME pressure-regulation, defining the causal sequences leading to ME pressure disregulation (MEPD)/otitis media with effusion (OME) and identifying mediational links that could be targeted by treatments to prevent or "cure" MEPD related disease expressions. That model has not been calibrated to the specifications of the human ME nor have any of its specific predictions been tested for applicability to clinical disease. The experiments included in this translational research project develop an empirical database for testing the predictions of the model at the levels of individual components and when fully assembled. Specifically, we will characterize the properties of gas exchange across the three main pathways that affect ME pressure, i.e. passive exchange across the tympanic membrane (TM) and middle ear mucosa (MEM), and active/passive exchange across the Eustachian tube (ET). Because protocols for testing ET function (ETF) in humans are generally limited to ears with a non- intact TM, we plan to expand existing tests and to develop new protocols for testing ears with an intact TM in the controlled environment of a pressure-chamber. Also, we will evaluate four hypotheses relevant to our description of MEPD mediated OM expression during a viral upper-respiratory tract infection (vURI); i.e. 1) constitutional ETF defines the risk of otological complications during a vURI; 2) transMEM inert gas exchange is increased by local, neurogenic inflammation; 3) MEM inflammation, edema and effusion develop at a specific critical ME underpressure of approximately -200 mmH2O, and 4) transMEM inert gas exchange is increased by MEM inflammation.

天然气储量、需求和中期天然气平衡 从猴子的研究结果，我们开发了一个多层次的，互动的，反馈模型来描述 中耳（ME）压力调节的效率和失调的病理生理后果。 该模型只需要系统的几何结构和所代表的物理化学性质的知识 气体和组织，以预测ME压力的行为和有利于在 正常和病理状态。如果有效，该模型允许测试先前提出的ME机制 压力调节，定义导致ME压力失调（MEPD）/中耳炎的因果顺序 与积液（OME），并确定中介联系，可以通过治疗，以预防或“治愈” MEPD相关疾病表达。该模型尚未根据人体ME的规格进行校准 也没有对它的任何具体预测进行临床疾病适用性的测试。实验包括 在这个转化研究项目中，开发了一个经验数据库，用于测试模型在 单个组件的水平和完全组装时的水平。具体来说，我们将描述的性质， 通过影响ME压力的三个主要途径进行气体交换，即通过 鼓膜（TM）和中耳粘膜（MEM），以及通过咽鼓管的主动/被动交换 管（ET）。由于用于测试人类ET功能（ETF）的方案通常限于具有非耳道的耳朵， 完整的TM，我们计划扩大现有的测试，并制定新的协议，测试耳朵与完整的TM在 压力室的受控环境。此外，我们还将评估与我们的研究相关的四个假设。 病毒性上呼吸道感染（vURI）期间MEPD介导的OM表达的描述;即1） 宪法ETF定义了vURI期间耳科并发症的风险; 2）transMEM惰性气体交换是 局部神经源性炎症增加; 3）MEM炎症、水肿和积液在特定的 临界ME负压约为-200 mmH 2 O，以及4）transMEM惰性气体交换增加 MEM炎症。