Role of animal models for percutaneous atrial septal defect closure

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.

Transvenous implantation of the Occlutech Atrial Flow Regulator: Preliminary results from swine models

“…The volume of flow across a fenestration is affected by pressure gradient, viscosity of the blood, and body surface area among others. We propose that using Poiseuille’s law (see Appendix ) allows us to quantify the volume of blood flowing through the device . The relative viscosity of blood with a hematocrit of 40 to 45 is between 2.5 and 4, we used 3 as our viscosity at 37°C and hematocrit of 45.…”

“…Pigs have been used for many years as models for medical research and particularly for ASD research. 7 Despite this, there are significant differences between porcine and human atrial septal geometry and structure. It is disappointing but not surprising, therefore, that one animal showed complete obliteration of the orifice of the AFR.…”

“…We propose that using Poiseuille's law (see Appendix 1) allows us to quantify the volume of blood flowing through the device. 7 The rela- • The Atrial Flow Regulator appears symmetrically placed, well-seated, with the right disc well-opposed to the underlying atrial septal wall. • The left disc is not fully apposed at its most cranial extent.…”

“…Pigs have been used for many years as models for medical research and particularly for ASD research . Despite this, there are significant differences between porcine and human atrial septal geometry and structure.…”

Angioscopic Evaluation of Atrial Septal Defect Closure Device Neo‐Endothelialization

“…The 6‐month duration was decided on the basis of the results of a small population of animal experiments that showed that the devices were sufficiently neo‐endothelialized after 3 to 6 months. 23 , 24 , 25 To date, neo‐endothelialization has not been assessed in vivo in humans, and the evidence to support the appropriate treatment duration is inadequate. Only limited numbers of autopsy cases and device extraction cases demonstrated the extent of neo‐endothelialization of closure devices in humans.…”