Surgical technique: establishing a pre-clinical large animal model to test aortic valve leaflet substitute

Abstract

To overcome current limitations of valve substitutes and tissue substitutes the technology of tissue engineering (TE) continues to offer new perspectives in congenital cardiac surgery. We report our experiences and results implanting a decellularized TE patch in nine sheep in orthotropic position as aortic valve leaflet substitute. Establishing the animal model, feasibility, cardiopulmonary bypass issues and operative technique are highlighted. side effect of lifelong anticoagulation. The lack of an ideal valve substitute has raised interest in alternative techniques, such as repairing the diseased valve rather than replacing it. In the past several years, the percentage of valve repair as compared to AVR has increased (1). For many of the aortic valve repair techniques, a patch is needed as substitute, partial or complete replacement or leaflet extension. So far various cusp tissue substitutes have been tested, but failed to fulfill the requirements for an optimal patch material. Currently used patch material for valve repairAn optimal patch material should be pliable, hemostatic and resistant to tearing, should not shrink or calcify, and should possibly not induce an inflammatory cascade. Since the late 1960s, attempts have been made to use biologic materials like fascia lata, dura mater and bovine pericardium with poor outcomes (4-6). An easily available source for valve repair is the autologous pericardium, which is widely used for partial or total cusp replacement or leaflet extension (7-10). Some groups propagate pretreatment with glutaraldehyde, which prevents secondary shrinking and calcification (9,10). On the other hand, untreated fresh autologous pericardium might possess true growth, but distensibility as well. Despite good short-and mid-term results, it is associated with a high degeneration rate in the long term (11)(12)(13)(14) and is associated with bacterial endocarditis (8,10,15). Bovine pericardium-used as leaflet extension-has been shown to be less effective as compared to autologous pericardium (16,17), and autologous pericardium has greater resistance to retraction. Since polytetrafluoroethylene (PTFE) was successfully used for right ventricular outflow graft reconstruction or in mitral leaflet position with good longterm results (18)(19)(20), it was applied as leaflet extension in the aortic valve position. Nosál' and coworkers reported 13 congenitally affected patients, with the youngest being 22 months old, in whom PTFE leaflet extensions were done with a follow-up till 30 months (21). However, there still remains a higher risk of endocarditis, and concerns have been raised about leaflet thickening and decreased mobility (18,22). Technical and scientific achievements in the field of tissue engineering (TE) may offer new perspectives with the potential of an off-the-shelf starter matrix for guided tissue regeneration. Study rationaleThe ultimate goal is to develop an aortic valve leaflet substitute which is physiological, durable and has the potential for growth, and test it in ...

Establishing a pre-clinical growing animal model to test a tissue engineered valved pulmonary conduit

“…Compared to a human, structural changes and calcification of a cardiac valve (primary outcome parameter) occurs much earlier in an ovine. Because 1 year of a sheep life roughly equals 7 years of a human's life 'long-term' outcome results may be acquired in shorter time periods (ratio 1:7); (II) From other pre-clinical experiments using off-theshelf de-cellularized TE patches (17,18) as aortic valve leaflet (19) we learned that the potential benefits of a thoracotomy outweighed those of a sternotomy, especially when considering a chronic study. According to our experience using a LLT via the fourth intercostal space (i) offers good exposure to the pulmonary trunk and the pulmonary valve, (ii) allows reliably the cannulation of the descending aorta and the right atrium via the right auricle and (iii) promotes early extubation and sufficient spontaneous breathing as postoperative pain is diminished in these animals normally lying on the sternum; (III) The exposure of the ascending aorta, clamping and infusion of cardioplegia is technically challenging in sheep due to the short size of the ascending aorta.…”