Sheep models in translational surgery.

Abstract

The selection of an animal model is tedious. One must consider several factors; one of these, of utmost importance, is the translational value of the animal model. The sheep, as a translational surgical model, possesses a multiple of advantages that makes it one of the preferred models in several research domains. Sheep are the state-of-the-art test models for cardiovascular research and safety studies required for approval of cardiovascular implantable devices; the sheep's heart size, cardiac muscle, heart valves and the mechanical, haemodynamic and coagulation parameters are very similar to humans. Furthermore, the pregnant sheep/lamb are robust models for studying neonatal adaptation and placental physiology due to its physiological similarities with humans. Its placental structure supports efficient gas exchange, resembling human oxygen transfer mechanisms. The ovine model is mainly used in studies of adaptation at birth, foetal physiology during labour and in congenital diaphragmatic hernia. The sheep model is also used in several orthopaedic pre-clinical models, mainly in the study of critical bone defects, cancellous bone healing, osteomyelitis and joint replacement surgeries. It is also a preferred model of bone healing in osteoporosis. Moreover, the sheep has gained popularity as a model of osteoarthritis (OA); it is a validated model of surgically induced OA. Several therapeutic modalities can be evaluated using validated outcome measures such as, kinetics, kinematics, imaging, repeated arthroscopic grading, synovial fluid analysis and biomarkers. The ovine model, because of its size, is the closest to humans for the evaluation of spinal surgery techniques, devices and spinal fusion biological enhancers/ cancellous graft replacement. Finally, we will outline the different specificities of sheep analgesia and anaesthesia. Challenges encountered in ruminant anaesthesia are mainly in relation with their digestive physiology that creates a high risk of regurgitation during anaesthesia and a hindrance of diaphragm/respiratory movements due to rumen repletion and meteorism. Fasting regimen and management of recovery should encompass strategies that limit the starving sensation and allow for reduced social isolation. Clarification of the interactions between scientific objectives and anaesthesia-analgesia protocols prevents conflicts between the ethics and the purpose of the experiment while allowing for development of model-specific anaesthesia and pain management protocols. The sheep has become a popular model because of its size, availability, robustness, cost and ease of handling. Furthermore, as a preclinical model, the same validated objective outcome measures used to measure success in humans can apply to sheep.