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.

我们要求资金购买用于呼吸，代谢和心血管的集成系统 从啮齿动物（大鼠和小鼠）中获取生理数据。该系统将允许醒着或 睡觉，不受约束的动物，以提供疾病模型的全面表征和 实验治疗的纵向作用。该系统的核心是整体体积学 来自数据科学国际的钱伯。这些允许同时获取实时生理数据 来自4种无动，未经麻醉的动物（每个腔室一只大鼠）。数据包括呼吸速率，潮汐量， 微小的通风，灵感时间，呼气时间。该系统还能够检测到呼吸停顿 （apneas）。每个室配备温度和相对湿度传感器，以更准确 计算潮汐量和微小通风。该传感器可以很容易地换成药物雾化器 允许使用气溶胶。此外，我们建议用特殊盖子获取通道 腔室内电缆以不损害空气紧密度的方式。这允许获取数据 来自配备SPO2红外传感器（Mouseox Plus，Starr Life Sciences）或电缆粘附的动物 导管（用于血液采样，模拟气道阻塞，E.T.C。）。室被气体喂 （氮，氧，二氧化碳）通过气体搅拌机（CWE掺入），允许创建 实验性混合物，以模拟缺氧，高氧或高碳酸盐。每个房间的气体流出是 分别采样（黑貂系统）和外发氧和二氧化碳水平用于测量 每只大鼠通过气体分析仪（CWE Incorporated）。这允许获取代谢参数（氧 消耗，二氧化碳产生，呼吸道交换比）与通气参数同时。 最后，每个室位于遥测接收器平台上。这将允许整合遥测数据 获取整个身体的功能，并使收集数据（例如 血压和葡萄糖，ECG，EEG，核心温度和交感神经活动。数据分析 软件还能够为每种动物进行视频录制，从而可以测量活动和 证实睡眠/唤醒时间。 该设备将用于支持几位研究人员的工作，其研究计划的重点是 与退伍军人相关的疾病。 Mihaela Teodorescu博士研究哮喘对系统性的影响 高血压和对缺氧的通气反应。她将使用设备将动物暴露于正常和 低氧空气，并获得呼吸道和心血管数据。罗伯特·康希姆（Robert Conhaim）博士研究 在正常空气，低氧条件下和间歇性下，肺内的微血管灌注分布 气道阻塞。 Robert Striker博士研究了包括HIV在内的各种侮辱中的免疫系统恢复。 Nathan Sandbo博士研究了特发性肺纤维化的分子机制。最后，达德利博士 Lamming将对雷帕霉素（MTOR）途径在与年龄相关的机理靶标的作用进行研究 啮齿动物中的肺部疾病。应用程序中概述了一系列正在进行的和计划的协作项目， 这将大大扩展这些计划的重点。所有这些项目对 退伍军人的健康和我们要求的完整性套件将有助于这些进步 富有成效和重要的项目，并激发与其他用户的协作努力。