Role of Inflammation and Ischemia after Implantation of Xenogeneic Pulmonary Valve Conduits: Histological Evaluation after 6 to 12 Months in Sheep

OBJECTIVE: Commercially available biological heart valve prostheses undergo degenerative changes, which finally lead to complete destruction. Here we evaluate the role of inflammation and ischemia after implantation of xenogeneic heart valve conduits (XPC) generated by novel concepts of tissue engineering. METHODS: Acellularized (a-)XPC and autologus re-seeded (s-)XPC were implanted into sheep. Samples were taken as follows: after acellularization (n = 2), after re-seeding (n = 2), 6 months (seeded/non-seeded: n = 3/5), 9 months (n = 2/5), and 12 months (n = 3/2) post implantation. Five native porcine conduits served as control. Using histological methods, samples were evaluated for pathological changes and existence/density of microvessels. RESULTS: Prior to implantation a-XPC were completely free of cells. Six months after implantation, leaflets and pulmonary arteries of s-XPC and a-XPC showed good endothelial surface coverage. Microvessel density within the myocardial cuffs and pulmonary vessel walls were comparable to control in all grafts. However, 6, 9 and 12 months after implantation pathological severe microvessel ingrowth, calcification and cellular infiltrations were observed on a-XPC and s-XPC valves, whereas myocardial cuffs and XPC-artery walls showed only mild degenerative alterations. CONCLUSIONS: Inflammatory reactions play a pivotal role in the degeneration of a-XPC and s-XPC. Thus, since ischemia seems to have little or no influence on this process, inflammation inductive factors should be the center of interest.