Movement-Responsive Cage for Simultaneous Pharmacology Studies in MiniPigs

DESCRIPTION (provided by applicant): Animal models for human disease are important tools for biomedical and pharmaceutical research. Pigs, like humans, develop hypertension, diabetes and cardiovascular disease and respond to stress by releasing hormones via the HPA axis. We propose to utilize pigs more effectively and humanely, by allowing multiple experiments to be conducted simultaneously in the same freely-moving subject, while reducing their stress associated with handling during dosing or collection of biofluids. This will be accomplished through a movement-responsive caging system that we propose to construct, called the "PigTurn". Like the "Raturn", a system we successfully developed for rodents, the PigTurn will enable automated programmed dosing, automated blood sampling, simultaneous electrocardiography, in vivo microdialysis and behavioral monitoring, thus multiplying the amount of data available from each experiment and providing correlations between pharmacokinetics and pharmacodynamics in the same subject. Pigs are important in preclinical studies of new drugs, not only for efficacy but also to determine absorption, distribution, metabolism, and elimination (ADME), and toxicity. Human and pig are far more similar in terms of anatomy and physiology than the mouse, rat or dog. We wish to create a prototype, movement-responsive cage for pigs weighing 10 to 30 kg, i.e. minipigs that are purpose-bred for research. The concept is based on our movement-responsive cage for rodents, which has been widely adopted in pharmaceutical research in an automated blood sampling and dosing machine ("Culex"). It would permit parallel studies in the same freely- moving animal because multiple test leads could be operated during the same period of time. Examples of such test leads include separate dosing and blood collection or biofluid catheters, temperature sensors, EEG and ECG leads and microdialysis lines. Inherent in the design is a behavioral monitor capable of continuously-recording clockwise or counterclockwise rotation and vertical movement. Acknowledging the differences between a rat and a pig, we will preserve the essential principles of the rodent cage while making a cage to safely accommodate a mobile pig connected to one or more test leads. The specific aims of Phase 1 are directed towards engineering, behavioral studies and construction of a prototype, with emphasis on the enclosure, movement-responsive mechanism, umbilical system to protect the test leads and the response of minipigs to these features. The long term goals (Phase 2) are to validate this tool with automated blood sampling, electrocardiology and other techniques directed towards simultaneous pharmacokinetics and pharmacodynamics. This device will have broad appeal among public research institutions, pharmaceutical companies, contract research organizations and other laboratories interested in simultaneously collecting biofluids, physiological data and behavior from pigs, or other large animals.