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

Wm S. Middleton Memorial Veterans Hosp, Madison WI

Investigators

Abstract

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.