title: Cardiac xenotransplantation technology provides materials for improved bioprosthetic heart valves.
abstract: OBJECTIVE
  Human subjects and Old World primates have high levels of antibody to galactose-α-1,3 galactose β-1,4-N-acetylglucosamine (α-Gal). Commercially available bioprosthetic heart valves of porcine and bovine origin retain the Gal antigen despite current processing techniques. Gal-deficient pigs eliminate this xenoantigen. This study tests whether binding of human anti-Gal antibody effects calcification of wild-type and Gal-deficient glutaraldehyde-fixed porcine pericardium by using a standard subcutaneous implant model.
  
  
  METHODS
  Expression of α-Gal was characterized by lectin Griffonia simplicifolia-IB4 staining. Glutaraldehyde-fixed pericardial disks from Gal-positive and Gal-deficient pigs were implanted into 12-day-old Wistar rats and 1.5-kg rabbits with and without prelabeling with affinity-purified human anti-Gal antibody. Calcification of the implants was determined after 3 weeks by using inductively coupled plasma spectroscopy.
  
  
  RESULTS
  The α-Gal antigen was detected in wild-type but not Gal-deficient porcine pericardium. Wild-type disks prelabeled with human anti-Gal antibody exhibited significantly greater calcification compared with that seen in antibody-free wild-type samples (mean ± standard error of the mean: 111 ± 8.4 and 74 ± 9.6 mg/g, respectively; P = .01). In the presence of anti-Gal antibody, a significantly greater level of calcification was detected in wild-type compared with GTKO porcine pericardium (111 ± 8.4 and 55 ± 11.8 mg/g, respectively; P = .005). Calcification of Gal-deficient pericardium was not affected by the presence of anti-Gal antibody (51 ± 9.1 and 55 ± 11.8 mg/g).
  
  
  CONCLUSIONS
  In this model anti-Gal antibody accelerates calcification of wild-type but not Gal-deficient glutaraldehyde-fixed pericardium. This study suggests that preformed anti-Gal antibody present in all patients might contribute to calcification of currently used bioprosthetic heart valves. Gal-deficient pigs might become the preferred source for new, potentially calcium-resistant bioprosthetic heart valves.
authors.affiliation: Department of Cardiothoracic Surgery, University College London, London, United Kingdom. mcgregor.christopher@mayo.edu
authors.forename: Christopher G A
authors.initials: CG
authors.lastname: McGregor
authors.forename: Alain
authors.initials: A
authors.lastname: Carpentier
authors.forename: Nermine
authors.initials: N
authors.lastname: Lila
authors.forename: John S
authors.initials: JS
authors.lastname: Logan
authors.forename: Guerard W
authors.initials: GW
authors.lastname: Byrne
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015478:Antigens, Heterophile / Q000096:biosynthesis / Q000276:immunology*; D001323:Autoantibodies / Q000008:administration & dosage; D001705:Bioprosthesis; D002114:Calcinosis / Q000276:immunology*; D005404:Fixatives; D005700:Galactosyltransferases / Q000172:deficiency / Q000235:genetics; D005976:Glutaral; D006350:Heart Valve Prosthesis; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects / Q000295:instrumentation*; D006801:Humans; D008856:Microscopy, Fluorescence; D010496:Pericardium / Q000276:immunology / Q000637:transplantation*; D037121:Plant Lectins; D011474:Prosthesis Design; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013552:Swine / Q000235:genetics; D013997:Time Factors; D014183:Transplantation, Heterologous; D014312:Trisaccharides / Q000096:biosynthesis / Q000276:immunology*
chemical_list: D015478:Antigens, Heterophile; D001323:Autoantibodies; D005404:Fixatives; C045475:Griffonia simplicifolia lectins; D037121:Plant Lectins; D014312:Trisaccharides; C076569:alpha-galactosyl epitope; D005700:Galactosyltransferases; C530267:alpha-1,3-galactosyltransferase 1, porcine; D005976:Glutaral