title: Glutaraldehyde-fixed bioprosthetic heart valve conduits calcify and fail from xenograft rejection.
abstract: BACKGROUND
  Glutaraldehyde fixation (G-F) decreases but likely does not eliminate the antigenicity of bioprosthetic heart valves. Rejection (with secondary dystrophic calcification) may be why G-F xenograft valves fail, especially in young patients, who are more immunocompetent than the elderly. Therefore, we sought to determine whether rejection of G-F xenograft occurs and to correlate this with graft calcification.
  
  
  RESULTS
  Ascending aortas/valves (from rats [syngeneic] or guinea pigs [xenogeneic]) were transplanted (fresh or after 48 hour of G-F) into the infrarenal aortas of young rat recipients for 20 days. A xenogeneic group was also treated with steroids until graft harvest. The valves and media/adventitia were scored blindly for inflammation (0 to 4). Percent graft infiltration by T cells/macrophages was determined (immunohistochemistry), and rat IgG ELISAs were performed. There was >3 times more valve inflammation, >10 times more valve T-cell/macrophage infiltrate, and >3 times antibody rise in the G-F xenogeneic groups compared with the fresh syngeneic or the G-F syngeneic groups (P<0.05). There was >2 times more adventitial inflammation and T-cell/macrophage infiltrate in the xenogeneic groups (P<0.05). Steroid treatment decreased inflammation and antibody rise in the xenogeneic groups (P<0.05). Correlation analysis revealed media/adventitia inflammation (P=0.02) and percent macrophage (P=0.01) infiltration to be predictors of calcification.
  
  
  CONCLUSIONS
  G-F xenografts have cellular/humoral rejection and calcify secondarily.
authors.affiliation: Division of Cardiac Surgery, University of Alberta, Edmonton, Canada.. rizmanji@shaw.ca
authors.forename: Rizwan A
authors.initials: RA
authors.lastname: Manji
authors.forename: Lin F
authors.initials: LF
authors.lastname: Zhu
authors.forename: Nimrit K
authors.initials: NK
authors.lastname: Nijjar
authors.forename: David C
authors.initials: DC
authors.lastname: Rayner
authors.forename: Greg S
authors.initials: GS
authors.lastname: Korbutt
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Churchill
authors.forename: Ray V
authors.initials: RV
authors.lastname: Rajotte
authors.forename: Arvind
authors.initials: A
authors.lastname: Koshal
authors.forename: David B
authors.initials: DB
authors.lastname: Ross
mesh_terms: D000818:Animals; D001705:Bioprosthesis; D002114:Calcinosis / Q000209:etiology* / Q000473:pathology; D002465:Cell Movement; D005976:Glutaral / Q000494:pharmacology* / Q000627:therapeutic use; D006084:Graft Rejection / Q000209:etiology* / Q000276:immunology; D006168:Guinea Pigs; D006350:Heart Valve Prosthesis; D007249:Inflammation / Q000188:drug therapy; D008264:Macrophages / Q000502:physiology; D011475:Prosthesis Failure; D051381:Rats; D013256:Steroids / Q000494:pharmacology / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000502:physiology; D014183:Transplantation, Heterologous; D014185:Transplantation, Isogeneic
chemical_list: D013256:Steroids; D005976:Glutaral