title: The pathology of fresh and cryopreserved homograft heart valves: an analysis of forty explanted homograft valves.
abstract: OBJECTIVE
  Tissue degeneration reduces the durability of aortic and pulmonary homograft heart valves. Homograft valves can evoke cellular and humoral immune responses that might be detrimental to the valve tissue. Analyzing explanted homograft valves helps in understanding the different factors that eventually lead to tissue degeneration.
  
  
  METHODS
  A total of 40 homografts was acquired from patients whose grafts had been explanted because of stenosis (n = 22), insufficiency (n = 8), paravalvular leakage (n = 4), other technical problems (n = 4), noncardiac death (n = 1), and stenosis with endocarditis (n = 1). The period of implantation varied from 14 days to 16 years (median, 4 years). Cryopreserved valves (n = 31) were, in the majority, derived from beating-heart donors, whereas the fresh valves were sterilized with antibiotics and stored at 4 degrees C for an average of 32 days. Four unimplanted cryopreserved valves, 1 native aortic valve, and 1 native pulmonary valve were used as references. Analysis included macroscopy, light microscopy with routine hematoxylin and eosin staining (cellularity and tissue structure), and immunohistochemical studies to allow identification of macrophages (CD68) and T lymphocytes (CD3), endothelial cells, leukocyte adhesion molecules (CD54, CD106, and CD62E), and immunoglobulin (IgG) and complement factor (C3) depositions. In situ hybridization for the Y chromosome was performed in 10 cases, with host-donor sex mismatch, to distinguish between host and donor cells. The outcomes of histology and immunohistochemistry were related to clinical factors, such as implantation time and reason for explantation.
  
  
  RESULTS
  In the first year after implantation, a strong reduction in cellularity of the valve tissue was observed, with almost acellular tissues after 1 year. Trilaminar tissue architecture disappeared with the same speed, whereas endothelial cells were almost absent in all explants. Macrophages and T lymphocytes were encountered in 85% and 78% of the leaflets, respectively. Expression of leukocyte adhesion molecules was low in almost all grafts, and IgG and C3 depositions were not increased. Valve tissue cellularity consisted mainly of ingrown host cells when the implantation time exceeded 1 year.
  
  
  CONCLUSIONS
  During the first year of implantation, homograft valves rapidly lose their cellular components and normal tissue architecture. A low-grade inflammatory response was observed, but no convincing evidence of immune-mediated injury was found.
mesh_terms: D000293:Adolescent; D000328:Adult; D001021:Aortic Valve / Q000276:immunology / Q000473:pathology* / Q000637:transplantation; D001024:Aortic Valve Stenosis / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015925:Cryopreservation; D006085:Graft Survival; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007223:Infant; D008853:Microscopy; D008875:Middle Aged; D011664:Pulmonary Valve / Q000276:immunology / Q000473:pathology* / Q000637:transplantation; D014019:Tissue Donors; D014184:Transplantation, Homologous; D014998:Y Chromosome / Q000235:genetics