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Abstract

Abstract

Reconstruction of the pulmonary valve and outflow tract is frequently needed to repair congenital defects. Current substitutes lead to graft failure and reoperation due to calcification, shrinkage, progressive insufficiency or transvalvular gradients, and relative growth of the patient compared to the valve. CorMatrix extracellular matrix (ECM), derived from decellularized, non-crosslinked small intestine submucosa (SIS) is used for general cardiac repairs and regenerates into normal cardiac tissue with growth potential. Previously, we showed that an ECM pulmonary valve leaflet remodeled into a neo-leaflet histologically similar to native valve architecture. In this study we used an ECM valved conduit for pulmonary valve replacement in an ovine model to demonstrate its potential to remodel into native tissue. A trileaflet valved conduit was produced from CorMatrix ECM sutured into a tube then intussuscepted to form a tube within a tube. At three equidistant points the inner tube was sutured to the outer tube forming three leaflets to guide unidirectional flow with physiologic opening and closing mechanics. Under cardiopulmonary bypass the ovine pulmonary valve and pulmonary artery section was removed and replaced with the ECM valved conduit. Valve function was evaluated by echocardiography post-operatively and at bi-monthly intervals until euthanasia at 3, 5, 8, and 12 months. Histological evaluation included H and E, Movat pentachrome, von Kossa, anti-CD31, and anti-eNOS. Our echocardiography results show that a pulmonary valve constructed from ECM opens and closes completely without regurgitation or stenosis for 12 months. Grossly, explanted valves appeared similar to native valves and were remodeling after 3 months with further progression to native morphology after 5, 8 and 12 months. Histological examination showed diffuse cellular infiltration by 3 months. At 5 months, collagen organization was increased and glycosaminoglycans were distributed throughout the middle of the leaflet. At 3 months, SEM and eNOS staining demonstrated a confluent and functional endothelial lining on the pulmonary artery and hinge regions of the valve. At 5 months, this lining extended to the center of the leaflet with confluent areas at the leaflet tip. At 8 and 12 months, a tri-layered structure similar to native valve architecture was demonstrated histologically by a Movat stain with a confluent endothelial lining demonstrated by eNOS and CD31 staining. The von Kossa stain showed an absence of calcific deposits at all time points except occasionally at the suture. These results demonstrate the potential of a CorMatrix ECM pulmonary valve to remodel into endothelialized tissue that is indistinguishable from the host’s native valve both grossly and histologically. Such a regenerated valve would be expected to improve patient outcomes since it remodels into native tissue with growth potential.

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/content/papers/10.5339/qproc.2012.heartvalve.4.81
2012-05-01
2020-09-20
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http://instance.metastore.ingenta.com/content/papers/10.5339/qproc.2012.heartvalve.4.81
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  • Accepted: 05 June 2012
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