Cardiac xenotransplantation technology provides materials for improved bioprosthetic heart valves

Christopher G.A. McGregor, Alain Carpentier, Nermine Lila, John S. Logan, Guerard W. Byrne

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Objectives: 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.

Original languageEnglish (US)
Pages (from-to)269-275
Number of pages7
JournalJournal of Thoracic and Cardiovascular Surgery
Volume141
Issue number1
DOIs
StatePublished - Jan 2011
Externally publishedYes

Bibliographical note

Funding Information:
Supported by the Mayo Clinic and the University of Paris Descartes, Assistance Publique Hôpitaux de Paris, and the Alain Carpentier Foundation .

Keywords

  • BHV
  • GGTA1
  • GSIB4
  • Griffonia simplicifolia-IB4
  • Ig
  • LVAD
  • PBS
  • bioprosthetic heart valve
  • galactose-α-1,3 galactose β-1,4-N-acetylglucosamine
  • immunoglobulin
  • left ventricular assist device
  • phosphate-buffered saline
  • α-1,3 galactosyltransferase
  • α-Gal

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