ShEEP Request for a Integrated Whole Body Plethysmograph, Metabolic and Cardiovascular System

ShEEP 请求集成全身体积描记器、代谢和心血管系统

• 批准号: 9796670
• 负责人: Mihaela Teodorescu
• 金额: --
• 依托单位: WM S. MIDDLETON MEMORIAL VETERANS HOSP
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-01 至 2019-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9796670
• 关键词: AIDS/HIV problem; Acute Lung Injury; Aerosols; Aging; Air; Algorithms; Anesthesia procedures; Animals; Apnea; Area; Asthma; Attenuated; Biological Sciences; Blood Glucose; Blood Pressure; Blood specimen; Body Temperature; Breathing; Bronchoconstriction; Carbon Dioxide; Cardiovascular Physiology; Cardiovascular system; Catheters; Collaborations; Computer software; Data; Data Analyses; Data Science; Diabetes Mellitus; Disease; Disease model; Electrocardiogram; Electrodes; Electroencephalography; Environmental air flow; Equipment; Exposure to; FRAP1 gene; Funding; Gases; Goals; HIV; Health; Healthcare; Hospitals; Humidity; Hypercapnia; Hyperoxia; Hypoxia; Immune system; Implant; International; Knowledge; Left; Lung; Lung diseases; Martes zibellina; Measurement; Measures; Metabolic; Molecular; Mus; Nebulizer; Nerve; Nitrogen; Obstructive Sleep Apnea; Oxygen; Oxygen Consumption; Pathway interactions; Perfusion; Pharmaceutical Preparations; Physiologic intraventricular pressure; Physiological; Plethysmography; Pressure Transducers; Production; Pulmonary Fibrosis; Pulse Oximetry; Rattus; Recovery; Regulation; Research; Research Personnel; Respiratory System; Respiratory physiology; Rodent; Rodent Model; Role; Sampling; Sheep; Signal Transduction; Site; Sleep; Sleep Wake Cycle; System; Systemic hypertension; Telemetry; Temperature; Tidal Volume; Time; Vascular Diseases; Veterans; Video Recording; Whole Body Plethysmography; Work; age related; airway obstruction; animal data; awake; data acquisition; data integration; design; effective therapy; experimental study; gas analyzer; idiopathic pulmonary fibrosis; innovation; metabolic rate; pressure; prevent; programs; respiratory; respiratory gas; response; restraint; sensor

We are requesting funding to purchase an integrated system for respiratory, metabolic and cardiovascular physiology data acquisition from rodents (rats and mice). This system will allow data recordings from awake or sleeping, unrestrained animals to provide comprehensive characterization of the disease model and longitudinal effects of experimental treatments. At the core of this system are Whole Body Plethysmography chambers from Data Sciences International. These allow simultaneous acquisition of real-time physiologic data from 4 unrestrained, unanesthetized animals (one rat per chamber). Data include respiratory rate, tidal volume, minute ventilation, inspiratory time, expiratory time. The system is also able to detect breathing pauses (apneas). Each chamber is equipped with temperature and relative humidity sensors for more accurate calculations of tidal volume and minute ventilation. This sensor can easily be swapped out for a drug nebulizer to allow for aerosol administration. Additionally, we propose to acquire chambers with special lids for passage of cables inside the chamber in a way that does not compromise air tightness. This allows for acquiring data from animals outfitted with a SpO2 infrared sensor (MouseOx Plus, Starr Life Sciences) or a cable-encased catheter (for blood sampling, simulating airway obstructions, e.t.c.). The chambers are fed with gases (nitrogen, oxygen, carbon dioxide) through a gas mixer (CWE Incorporated) that allow for creation of experimental mixtures to simulate hypoxia, hyperoxia or hypercapnia. The gas outflow of each chamber is sampled separately (Sable Systems) and the outgoing oxygen and carbon dioxide levels are measured for each rat by a gas analyzer (CWE Incorporated). This allows acquisition of metabolic parameters (oxygen consumption, CO2 production, respiratory exchange ratio) simultaneously with ventilatory parameters. Lastly, each chamber is situated on a telemetry receiver platform. This will allow integration of telemetry data acquisition capabilities into the Whole Body Plethysmograph, and make it possible to collect data such as blood pressures and glucose, ECG, EEG, core temperature and sympathetic nerve activity. The data analysis software is also capable of video recording for each animal, which allows for measurement of activity and corroborate sleep/wake times. This equipment will be used to support the work of several investigators whose research programs focus on diseases of high relevance to the Veterans. Dr. Mihaela Teodorescu studies effects of asthma on systemic hypertension and ventilatory response to hypoxia. She will use the equipment to expose animals to normal and hypoxic air, and to acquire respiratory and cardiovascular data. Dr. Robert Conhaim studies regulation of microvascular perfusion distribution within the lung under normal air, hypoxic conditions, and under intermittent airway occlusion. Dr. Robert Striker investigates immune system recovery from various insults, including HIV. Dr. Nathan Sandbo studies the molecular mechanisms of Idiopathic Pulmonary Fibrosis. Finally, Dr. Dudley Lamming will conduct studies on the role of mechanistic target of rapamycin (mTOR) pathway in age-related lung disease in rodents. An array of ongoing and planned collaborative projects is outlined in the application, which will vastly expand the focus of these programs. All of these projects have significant implications for Veterans' health, and the plethysmography suite we are requesting will facilitate the progress of these productive and important projects, as well as stimulate collaborative efforts with other users.

我们正在申请资金购买一个呼吸、代谢和心血管综合系统 从啮齿动物（大鼠和小鼠）采集生理学数据。该系统将允许数据记录从清醒或 睡眠、不受约束的动物，以提供疾病模型的全面表征， 实验治疗的纵向效应。该系统的核心是全身体积描记术 数据科学国际（Data Sciences International）这些允许同时采集实时生理数据 来自4只未受限制的未麻醉动物（每个室一只大鼠）。数据包括呼吸频率、潮气量、 分钟通气量、吸气时间、呼气时间。该系统还能够检测呼吸暂停 （呼吸暂停）。每个箱体都配有温度和相对湿度传感器， 计算潮气量和每分钟通气量。这种传感器可以很容易地交换了药物喷雾器 以允许气雾剂施用。此外，我们建议购买带有特殊盖子的通道室 电缆在室内的方式，不损害气密性。这允许获取数据 来自配备SpO 2红外传感器（MouseOx Plus，Starr Life Sciences）或电缆包裹的动物 导管（用于血液采样、模拟气道阻塞等）。腔室被注入气体 通过气体混合器（CWE Incorporated）将气体（氮气、氧气、二氧化碳）混合，该气体混合器允许产生 模拟缺氧、高氧或高碳酸血症的实验混合物。每个腔室的气体流出量为 分别取样（Sable系统），并测量输出的氧气和二氧化碳水平， 每只大鼠通过气体分析仪（CWE Incorporated）测量。这允许采集代谢参数（氧气 消耗量、CO2产生量、呼吸交换率）与净化参数同时进行。 最后，每个腔室都位于遥测接收器平台上。这将允许整合遥测数据 采集功能到全身体积描记器，并使其能够收集数据，如 血压和葡萄糖、ECG、EEG、核心温度和交感神经活动。数据分析 软件还能够对每只动物进行视频记录，这允许测量活动， 证实睡眠/醒来时间。 这些设备将用于支持几名研究人员的工作，他们的研究计划侧重于 与退伍军人相关的疾病。Mihaela Teodorescu博士研究了哮喘对全身的影响 高血压和对缺氧的代偿反应。她将使用这些设备将动物暴露在正常和 低氧空气，并获取呼吸和心血管数据。Robert Conhaim博士研究了 在正常空气、低氧条件下和间歇性低氧条件下肺内微血管灌注分布 气道阻塞Robert Striker博士研究免疫系统从各种侮辱中恢复，包括艾滋病毒。 博士Nathan Sandbo研究特发性肺纤维化的分子机制。最后，达德利医生 Lamming将研究雷帕霉素（mTOR）通路的机制靶点在年龄相关性 啮齿类动物的肺病申请中概述了一系列正在进行和计划进行的合作项目， 这将极大地扩大这些项目的重点。所有这些项目都对 退伍军人的健康，和体积描记套件，我们要求将促进这些进展 我们的目标是为生产性和重要的项目提供支持，并促进与其他用户的合作努力。