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，需求和中耳气体余额从猴子的研究结果来看，我们开发了一种多层次，互动的反馈模型来描述中耳（ME）压力调节的效率和疏离的病理生理后果。该模型仅需要系统几何形状和代表的理化特性的知识气体和组织预测我压力的行为以及有利于过渡的条件正常和病理状态。如果有效，该模型允许测试我先前建议的我的机制压力调节，定义导致压力脱离的因果序列（MEPD）/中耳炎培养基与积液（OME）一起确定可以通过治疗方法来预防或“治愈”的中介联系 MEPD相关疾病表达。该模型尚未校准人类ME的规格也没有对其针对临床疾病的适用性进行测试。实验包括在这个翻译研究项目中，开发了一个经验数据库，用于测试模型的预测单个组件的水平以及完全组装时。具体而言，我们将表征跨三个影响我压力的主要途径，即被动交换鼓膜膜（TM）和中耳粘膜（MEM），以及在Eustachian上进行主动/被动交换管（ET）。因为人类测试ET函数（ETF）的方案通常仅限于耳朵完整的TM，我们计划扩展现有测试，并开发新的协议，以在压力舱的控制环境。此外，我们将评估与我们的四个相关的假设 MEPD在病毒上呼吸道感染期间的MEPD介导的OM表达（VURI）；即1）宪法ETF定义了Vuri期间耳鼻肌并发症的风险； 2）TransMem惰性气体交换是通过局部神经源性炎症增加； 3）MEM炎症，水肿和积液在特定的关键的我的压力大约为-200 mmh2o，而4）透射惰性气体交换增加 MEM炎症。