Implementation of the three R's Tenet to primate research: application of a new device as a means of long-term enteral administration of drugs or nutritional supplementation

In experimental research entailing the use of animals, the application of the three R's Tenet (reduction, refinement, replacement) is now diligently adhered to by the scientific community and incorporated in an increasing number of legal frameworks. In particular, the refinement of procedures, by theidentification of strategies that enable the non-stressful administration of food or drugs to nonhuman primates exposed to long-term studies, is strongly recommended. Neuron pig-to-primate xenotransplantation is a complex animal model, requiring oral treatments (and, occasionally, nutritional supplementation) for several months. Sixteen 4–8 year-old purpose-bred cynomolgus monkeys (Macaca fascicularis), weighing between 2.6 and 4.4 kg were used as recipients in xenotransplantation studies and underwent surgical positioning of a surgical placed gastrostomy (SPG). The device consists of an injection port placed subcutaneously on the anterior chest wall and of a silicon valved catheter inserted into the gastric lumen. The device was left in place for a period ranging between 1 and 12 months. In six cases, the SPG was successfully utilized for several months, until the experimental end-point was reached, avoiding the forced handling of nonhuman primates postoperatively. In six cases, the SPG had to be removed prior to reaching the end-point due to local infection at the site of implant that promptly regressed with SPG removal and antibiotic treatment. In two cases, the SPG-implanted primates were euthanized for reasons unrelated to the SPG or the xenotransplantation procedure. Finally, in two ongoing animals the SPG implanted prior to xenotransplantation is currently utilized after more than 3 months in the absence of any complication. The SPG device described minimizes the forced handling of nonhuman primates, otherwise needed to ensure the oral administration of substances by gavage. In this light, the device represents an effective refinement that fully complies with the three R's tenet, that should be considered by Primate Centres exposing nonhuman primates to long-term daily oral administration.