Medical training of baboons after orthotopic cardiac xenotransplantation
Elisabeth Neumann1,2, Julia Radan1,2, Maren Mokelke1,2, Rongrui Na 1, Ines Buttgereit1, Martin Bender1,3, Bruno Reichart1, Anna Oblasser-Mirtl4, Jan-Michael Abicht1,3, Matthias Längin1,3.
1Walter Brendel Centre of Experimental Medicine, LMU Munich, Munich, Germany; 2Department of Cardiac Surgery, University Hospital, LMU Munich, Munich, Germany; 3Department of Anaesthesiology, University Hospital, LMU Munich, Munich, Germany; 4Animal Training Center, Rohrbach-Steinberg, Austria
Introduction: Recently, we demonstrated survival for up to 6 months after pig-to-baboon orthotopic heart transplantation. For permission of clinical application of cardiac xenotransplantation, longer survival periods might be requested by the regulatory authorities (FDA/EMA). In Upper Bavaria, Germany, the prerequisite for long-term experiments is the removal of the swivel/tethering system to allow housing with other baboons. Therefore, the main objective of our medical training is the oral intake of drugs. Previously, drugs were mainly hidden in various types of juices. Here we report preliminary results after consulting a professional animal trainer to improve the staff’s training skills.
Methods: Two baboons were taught to perform specific tasks on command and were rewarded with positive reinforcers (e.g. dried fruits) shortly before and after cardiac xenotransplantation. With this so-called operant conditioning oral intake of drugs was trained, as well as other behaviors, such as movement to a desired position, saliva collection, i.m.- injections to prepare the animals for future anesthetic injections and i.v.- injections. The training not only aimed to prepare the animals for necessary medical procedures (medical training) but also served as valuable enrichment.
Results: Both baboons successfully ingested drugs including Pantoprazole, Aspirin, MMF and Rapamycin. The drugs were not mixed in juices or other treats, in spite of the bitter taste of MMF and rapamycin. The success rate was an average of 95% in baboon A and 80% in baboon B, and target drug levels for MMF (2 - 4 µg/l) and rapamycin (4 - 10 ng/l) were reached. Both baboons were successfully trained to receive i.m.-injections with saline solution into their gluteal muscles, which will be necessary in sedation for weekly medical examinations once the swivel/tethering system is removed. First attempts to collect blood from the awake baboons’ forearms were also successful. Other trained behaviors, such as target training, did not specifically function as medical training but provided as social, cognitive and sensory enrichment, helped facilitating daily handling and establishing a good animal-caretaker relationship.
Conclusion: Medical training of baboons is possible and desirable, even under the conditions of a preclinical cardiac xenotransplantation project.
Supported by the Deutsche Forschungsgemeinschaft (TRR127).