Gas Supply, Demand and Middle Ear Gas Balance

气体供应、需求和中耳气体平衡

基本信息

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
项目类别：
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

项目摘要

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.

气体供应、需求和中耳气体平衡根据对猴子的研究结果，我们开发了一个多层次、交互式、反馈模型来描述中耳（ME）压力调节的效率以及失调的病理生理后果。该模型仅需要了解系统几何形状和所代表的物理化学性质气体和组织来预测 ME 压力的行为以及有利于之间转变的条件正常和病理状态。如果有效，该模型允许测试之前建议的 ME 机制压力调节，定义导致 ME 压力失调 (MEPD)/中耳炎的因果序列积液（OME）并确定可以通过治疗来预防或“治愈”的中介联系 MEPD 相关疾病表达。该模型尚未根据人类 ME 的规格进行校准也没有测试其任何具体预测是否适用于临床疾病。实验包括在这个转化研究项目中，开发一个经验数据库，用于测试模型的预测各个组件的水平以及完全组装时的水平。具体来说，我们将表征影响 ME 压力的三个主要路径之间的气体交换，即跨过鼓膜 (TM) 和中耳粘膜 (MEM)，以及跨咽鼓管的主动/被动交换管（ET）。因为用于测试人类 ET 功能 (ETF) 的协议通常仅限于具有非完整的 TM，我们计划扩展现有的测试并开发新的协议来测试耳朵中具有完整的 TM 压力室的受控环境。此外，我们将评估与我们相关的四个假设病毒上呼吸道感染 (vURI) 期间 MEPD 介导的 OM 表达的描述；即 1) 宪法 ETF 定义了 vURI 期间发生耳科并发症的风险； 2) transMEM惰性气体交换为因局部神经源性炎症而增加； 3）MEM炎症、水肿和积液在特定的时间发生临界 ME 负压约为 -200 mmH2O，并且 4) transMEM 惰性气体交换增加 MEM 炎症。