Chronic orthotopic aortic valve implantation model

The ideal animal model to assess implanted prosthetic aortic valves has yet to be universally accepted. The majority of mechanical valves are used for aortic valve replacement (AVR), yet historically animal models have provided data mainly after mitral valve implantation, due to the poor survival of animals undergoing AVR. Proposed regulations will require data from site-specific models. Thus, we modified previously reported chronic ovine models used for orthotopic implantation of aortic valves, to conduct preclinical aortic valve evaluation and to establish a predictive animal model needed for safety, hemodynamics, pathology and handling.

Fourteen sheep underwent AVR with 19 mm mechanical valves. Each animal was placed on cardiopulmonary bypass and the prosthetic valve implanted using a complete transverse ascending aortic transection. Hemodynamic data and aortography were obtained intraoperatively and again after 20 weeks, at which time hemodynamic studies, aortography, and pathological examination were performed.

There were two operative deaths, but no significant complications in the other 12 sheep, 11 of which survived for 20 weeks. One animal died two weeks before sacrifice due to valve thrombosis. Chronic hemodynamic and aortographic data were within normal limits for all 11 sheep, and gross pathology of the implanted valve revealed no abnormalities.

This study demonstrated the feasibility of the ovine model for orthotopic AVR, thus allowing greater confidence in the predictive value of in vivo hemodynamic and angiographic data gathered before clinical trials. Compared with other species, this ovine model provided improved rates of morbidity and mortality, reproducibility, ease of postoperative care, availability and acceptable anatomical similarities to humans. Future aortic valve studies at Medtronic will build on this knowledge base, making ovines - with this surgical technique - our animal model of choice.