This award aims to reduce the number of rats and rabbits in cardiac injury research by establishing protocols to generate a cardiac injury in vitro using living myocardial slices (LMSs).
Cardiac injury research has a heavy reliance on animal models, particularly rats and rabbits, due to a lack of in vitro models that accurately replicate the complexity of the heart. In vivo studies of ischemia temporarily block an artery under general anaesthesia, to replicate the temporary loss of blood supply, and the effects are then observed after blood flow is restored. These studies are classified as severe under the UK’s Animals (Scientific Procedures) Act 1986 because of the level of suffering caused. Professor Cesare Terracciano and colleagues have previously developed LMSs, where thin heart slices from mammals are kept in culture and are viable for up to five days. Using slice culture preserves the 3D tissue structure and cellular heterogeneity of the heart, providing a better in vitro representation of the organ compared to other in vitro models, which are typically 2D. LMSs can be produced from a number of mammals, including rats, rabbits and humans, and each heart can be used to prepare up to 8, 15 and 50 slices respectively.
Studying cardiac injuries in the LMS currently requires the injury to be induced in the animal before the tissue slices are prepared. Cesare will optimise techniques to generate the injury in vitro, using cryoinjury to replicate myocardial necrosis and an ischemic solution to induce global ischemia/reperfusion. The processes leading to heart failure will also be examined by mechanically overloading the tissue. Workshops will be conducted at Cesare’s laboratory to disseminate and build confidence in the model and injury techniques.
van der Velden J et al. (2022). Animal models and animal-free innovations for cardiovascular research: current status and routes to be explored. Consensus document of the ESC Working Group on Myocardial Function and the ESC Working Group on Cellular Biology of the Heart. Cardiovascular Research, in press. doi: 10.1093/cvr/cvab370