Role of animal models for percutaneous atrial septal defect closure

Zakaria Jalal, Pierre-Emmanuel Seguela, Alban-Elouen Baruteau, David Benoist, Olivier Bernus, Olivier Villemain, Younes Boudjemline, Xavier Iriart, Jean-Benoit Thambo

Abstract

As for any preclinical development of new implantable device, bench testing has been followed by experimental studies on large animal models for the development of atrial septal defect closure devices. Various models have been used according to studied species (porcine, ovine or canine model) and whether the septal defect was percutaneously or surgically created. Animal models of percutaneous atrial septal defect closure aim to assess the healing process and device endothelialisation, as well as the development of magnetic resonance imaging guided procedures, the short-term effects of volume overload on right ventricular contractility through haemodynamic studies and the understanding of other complications such as nickel hypersensitivity. Each technique has its own advantages and drawbacks, and leads to different punch-related, acute septal injuries that could have an effect on the healing process after device implantation. It has been suggested that some long-term, major device-related complications such as thrombosis or infective endocarditis may be associated with an inappropriate healing process or insufficient endothelialisation of the device, leading industrial companies to pay a great deal of attention to the healing process. Tissue reactions in animal models were shown to adequately reproduce the healing response after device implantation in humans, with an endothelial device coverage observed as early as 30 days after implantation and complete after 3 to 6 months. Research perspectives may evaluate both animal models and in-vitro studies in parallel with a view to clarify the endothelialisation process using human endothelial cells through in-vitro experiments. Self-sensing device for detecting the presence of endothelial cells on the surface of intracardiac occluders and high-resolution imaging techniques that could non-invasively assess the complete endothelialisation of a device would also be promising tools which would need large animal models studies before their clinical application.