title: Is the tricuspid position suitable for testing replacement bioprosthetic valves in the sheep model?
abstract: OBJECTIVE
  Glutaraldehyde may promote calcification in xenograft tissue by the action of toxic aldehyde group residues involved in the cross-link process. Post-fixation treatment with homocysteic acid (HA) neutralizes this toxicity by bonding aldehyde groups, and enhances biocompatibility on the basis of strongly electronegative sulfonic groups. Previous studies in a rat subcutaneous model showed significant long-term mitigation of mineralization of glutaraldehyde-fixed pericardium treated with HA. This study aimed to assess the anticalcific efficacy of HA in a valvular implant in growing sheep, and establish if the tricuspid position is suitable for testing replacement bioprosthetic valves.
  
  
  METHODS
  Eleven stented 25 mm Pericarbon bioprostheses (seven HA-treated, four standard) were implanted in the tricuspid position of growing sheep. Infective endocarditis occurred in four prostheses. Among the remaining seven, three (two HA-treated, one standard) were explanted at 91 days (mid-term), and four (two HA-treated, two standard) at 140-141 days (long-term). All explants were studied by gross, X-ray, light, transmission and scanning electron microscopy, as well as by atomic absorption spectroscopy.
  
  
  RESULTS
  No histological and ultrastructural difference in tissue preservation were observed between HA-treated and standard Pericarbon bioprostheses, either in the mid or long term. The mean calcium content of mid-term HA-treated explants was 9.55 mg/g compared with 16.26 mg/g in mid-term standard explants. Only one late standard explant failed as a result of severe stenosis caused by massive dystrophic calcification. Among four late explants, two showed significant increase in mineralization (HA-treated, 87.45 mg/g; standard, 181.20 mg/g), while two showed calcium contents similar to those in mid-term explants (HA-treated, 11.96 mg/g; standard, 17.32 mg/g).
  
  
  CONCLUSIONS
  Post-fixation treatment with HA preserves structural properties after tricuspid implantation in growing sheep. The tricuspid implant in the sheep model failed to reproduce remarkable accelerated progressive calcification in all xenografts so as to demonstrate a significant difference between HA and standard explants. The tricuspid position for testing replacement bioprosthetic valves should be abandoned, and investigations repeated with the prosthesis in the mitral position.
authors.affiliation: University of Padua and Modena-Reggio Emilia, Sorin Biomedica-Cardio, Saluggia, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Pettenazzo
authors.forename: G
authors.initials: G
authors.lastname: Thiene
authors.forename: A M
authors.initials: AM
authors.lastname: Gatti
authors.forename: E
authors.initials: E
authors.lastname: Pasquino
authors.forename: E
authors.initials: E
authors.lastname: Talenti
authors.forename: G
authors.initials: G
authors.lastname: Noera
authors.forename: T
authors.initials: T
authors.lastname: Bottio
authors.forename: M
authors.initials: M
authors.lastname: Valente
mesh_terms: D000818:Animals; D001705:Bioprosthesis; D002114:Calcinosis / Q000378:metabolism / Q000517:prevention & control*; D002118:Calcium / Q000378:metabolism*; D006085:Graft Survival / Q000187:drug effects; D019918:Heart Valve Prosthesis Implantation / Q000379:methods*; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D023421:Models, Animal; D051381:Rats; D012756:Sheep; D013997:Time Factors; D014261:Tricuspid Valve / Q000737:chemistry / Q000473:pathology* / Q000637:transplantation*
chemical_list: D006710:Homocysteine; C007956:homocysteic acid; D002118:Calcium