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

我们正在申请资金，以购买呼吸、代谢和心血管的综合系统。 从啮齿动物(大鼠和小鼠)获取生理学数据。该系统将允许从唤醒或 睡眠，无拘无束的动物，提供全面的疾病模型和特征 试验性处理的纵向效应。该系统的核心是全身脉搏图 来自数据科学国际的钱伯斯。这些允许同时采集实时生理数据 取自4只不受限制、未麻醉的动物(每舱一只大鼠)。数据包括呼吸频率、潮气量、 分钟通气量、吸气时间、呼气时间。该系统还能够检测到呼吸暂停 (呼吸暂停)。每个房间都配备了温度和相对湿度传感器，以便更准确 潮气量和分钟通气量的计算。这个传感器可以很容易地换成药物雾化器。 以允许使用气雾剂。此外，我们建议购买装有特殊盖子的舱室以供通过。 在不影响气密性的情况下将电缆放置在腔室内。这允许获取数据 来自配备了SpO2红外传感器(MouseOx Plus，Starr Life Sciences)或电缆包裹的动物 导管(用于采血，模拟呼吸道阻塞等)。房间里充斥着气体 (氮气、氧气、二氧化碳)通过气体混合器(CWE公司)，允许产生 模拟低氧、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 分开采样(Sable Systems)，并测量输出的氧气和二氧化碳水平 每只大鼠使用气体分析仪(CWE公司)。这允许获取代谢参数(氧气 消耗量、二氧化碳产生量、呼吸交换率)与换气参数同时进行。 最后，每个腔体都位于遥测接收平台上。这将允许集成遥测数据 采集能力进入全身心搏图，并使收集数据成为可能，如 血压和血糖、心电、脑电、核心体温和交感神经活动。数据分析 软件还能够为每种动物录制视频，这允许测量活动和 确认睡眠/醒来时间。 该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 与退伍军人高度相关的疾病。米哈埃拉·特奥多雷斯库博士研究哮喘对全身的影响 高血压和低氧呼吸反应。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。罗伯特·康海姆博士研究 正常空气、低氧和间歇性条件下肺内微血管灌注量分布 呼吸道阻塞。罗伯特·斯特克博士研究了免疫系统从各种侮辱中恢复的情况，包括艾滋病毒。 内森·桑博博士研究特发性肺纤维化的分子机制。最后，达德利博士 Lamming将研究雷帕霉素(MTOR)途径的机械靶在年龄相关中的作用 啮齿动物的肺部疾病。应用程序中概述了一系列正在进行和计划中的协作项目， 这将极大地扩大这些项目的重点。所有这些项目都对 退伍军人健康，以及我们要求的体积测量套件将促进这些方面的进展 多产和重要的项目，以及激发与其他用户的协作努力。

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.