117.2: Medical training of baboons in orthotopic cardiac xenotransplantation

Introduction: With the clinical application of cardiac xenotransplantation drawing nearer, longer survival periods in the preclinical orthotopic cardiac pig-to-baboon-model 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, the cooperation during medical and husbandry procedures, is the reliable oral intake of drugs. Here we report preliminary results after consulting a professional animal trainer to improve the staff’s training skills. Methods: Four baboons were taught to perform specific tasks on command and were rewarded with positive reinforcers (e.g. dried fruits) before and after cardiac xenotransplantation. With this so-called positive reinforcement training oral intake of drugs was trained, as well as movement to a desired position, saliva collection, i.m.-injections and other behaviors. A training session and its success (e.g. date, duration of a training session, first performance of a desired behavior, etc.) was documented on training protocols during or shortly after a training session. Results: The baboons were trained on 114 ± 32 days; training sessions (TS) for each behavior lasted 5 ± 3 minutes. Training of oral drug intake was successful in all animals for some drugs (e.g. aspirin and ondansetron). Only one of four baboons learned to take the bitter tasting mycophenolate mofetil (MMF) in sufficient amounts (109 TS required). All four baboons learned to move to a desired position on command (8 ± 6 TS required) and tolerated saliva collection (24 ± 19 TS required). Two baboons also learned to voluntarily accept i.m.-injections with saline solution (25 and 33 TS, respectively). During medical training, positive socio-communicative behavior patterns (e.g. lip smacking) became more frequent, whereas undesirable behavior patterns (e.g. leaving of training position) did not increase, indicating a positive effect on the animal-trainer-relationship. Conclusion: We conclude that medical training of baboons is possible even under the conditions of a preclinical cardiac xenotransplantation experiment. In comparison to other behaviors, oral ingestion of MMF is very difficult and time consuming to train in our experimental setting; particularly, consistent intake necessary for long-term experiments seems to be out of reach with a training program based on positive reinforcement alone. Furthermore, medical training is an invaluable tool for trust building and enrichment. German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) TRR 127. German Primate Center (Deutsches Primatenzentrum, DPZ). Walter Brendel Centre of Experimental Medicine. Animal Training Center (ATC).