Triple immunosuppression reduces mononuclear cell infiltration and prolongs graft life in pig-to-newborn baboon cardiac xenotransplantation

O. P. Minanov, J. H. Artrip, M. Szabolcs, P. A. Kwiatkowski, U. Galili, S. Itescu, Robert E. Michler

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Objective: Pig hearts transplanted into unmedicated newborn baboons do not undergo hyperacute rejection by preformed xenoantibody and complement. These grafts are rejected at days 3 to 4 in association with the infiltration of macrophages and natural killer cells. We investigated whether an immunosuppressive regimen used widely in cardiac allotransplantation could reduce this cellular response and prolong xenograft life. Methods: Ten newborn baboons underwent heterotopic pig cardiac xenotransplantation. Five baboons were immunosuppressed with mycophenolate mofetil (100 mg/kg), methylprednisolone acetate (0.8 mg/kg), and cyclosporine A (INN: ciclosporin; 10 mg/kg). Xenograft rejection was studied by light microscopy and immunofluorescence. The induced humoral response to porcine xenoantigens was documented by enzyme-linked immunosorbent assay using synthetic α-1,3- galactosyl epitopes coupled to bovine serum albumin. Results: Graft life was extended from a mean of 3.6 ± 0.5 days (n = 5) to a mean of 6.2 ± 1.1 days (n = 5, p = 0.01). In comparison with controls, explanted grafts from medicated baboons demonstrated reduced infiltration with natural killer cells and macrophages, but increased evidence of complement-mediated rejection substantiated by increased deposition of immunoglobulin M, complement, and fibrin. In all baboons receiving transplants, levels of both immunoglobuliu M and immunoglobulin G anti-galactose were significantly increased after transplantation, with immunoglobulin G levels remaining persistently elevated. Conclusions: These results indicate that cyclosporine-based triple immunosuppression marginally prolonged xenograft survival and appears to have reduced the natural killer cell and macrophage infiltrates. The immunosuppressive protocol, however, was not adequate to prevent the induced immunoglobulin M humoral response and prevent complement-mediated graft injury.

Original languageEnglish (US)
Pages (from-to)998-1006
Number of pages9
JournalJournal of Thoracic and Cardiovascular Surgery
Volume115
Issue number5
DOIs
StatePublished - 1998
Externally publishedYes

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Heterologous Transplantation
Papio
Immunosuppression
Swine
Transplants
Heterografts
Natural Killer Cells
Cyclosporine
Macrophages
Immunosuppressive Agents
Immunoglobulin M
Immunoglobulin G
Heterophile Antigens
Heterophile Antibodies
Mycophenolic Acid
Bovine Serum Albumin
Fibrin
Galactose
Fluorescence Microscopy
Epitopes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Triple immunosuppression reduces mononuclear cell infiltration and prolongs graft life in pig-to-newborn baboon cardiac xenotransplantation. / Minanov, O. P.; Artrip, J. H.; Szabolcs, M.; Kwiatkowski, P. A.; Galili, U.; Itescu, S.; Michler, Robert E.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 115, No. 5, 1998, p. 998-1006.

Research output: Contribution to journalArticle

Minanov, O. P. ; Artrip, J. H. ; Szabolcs, M. ; Kwiatkowski, P. A. ; Galili, U. ; Itescu, S. ; Michler, Robert E. / Triple immunosuppression reduces mononuclear cell infiltration and prolongs graft life in pig-to-newborn baboon cardiac xenotransplantation. In: Journal of Thoracic and Cardiovascular Surgery. 1998 ; Vol. 115, No. 5. pp. 998-1006.
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AU - Kwiatkowski, P. A.

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AU - Itescu, S.

AU - Michler, Robert E.

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