Abstract 2981: Orthotopic Implantation of Decellularized Allogenic Aortic Valves in the Subcoronary Position: Preclinical Testing
Objective: Successful animal and clinical implantation of decellularized heart valves has been performed in the pulmonary position. For the aortic position with the high hemodynamic demands of the systemic circulation and the challenging implantation procedure comparable results have yet not been achieved.
Methods: Allogenic aortic valves (n=10) were decellularized using detergents (dAV). Five prostheses were analyzed for decellularization quality and scaffold preservation. Five valves were orthotopically implanted in juvenile sheep in a subcoronary technique. After 5 months, echocardiography, immunohistology, histology, electron microscopy and western blot (WB) were used for analysis.
Results: All animals survived the follow-up with increased body weight (38.8±2.8 vs. 56.0±2.6kg, p<0.001). After implantation, 3 dAV showed negligible and 2 other minor insufficiency (I°), which remained unchanged at explantation. Effective orifice area increased slightly (1.1±0.2 vs. 1.6±0.3cm2, p=0.051). Explanted dAV showed excellent macroscopy (n=4) with minor soft tissue nodula observed at the free cusp margins of only one dAV. No valve showed any signs of thrombosis or calcification. The microscopical cusp architecture was preserved with an almost complete endothelial repopulation as confirmed by vWF+/CD31+-staining, WB of endothelial markers (eNOS/vWF), and SEM. Partial interstitial reseeding with vimentin+-cells was noted. Quantitative measurement of collagen-I, laminin and elastin (WB) demonstrated preserved scaffold composition as compared to native tissue.
Conclusion: For the first time, excellent valve function and preserved structural integrity of decellularized AV up to 5 months after subcoronary implantation was demonstrated in juvenile sheep. Advanced endothelial and beginning interstitial repopulation and tissue remodelling under the high shear stress milieu of the aortic valve encourage further long-term studies and clinical investigation.