Effective antiplatelet therapy does not prolong transgenic pig to baboon cardiac xenograft survival

Johannes M. Schirmer, David N. Fass, Guerard W. Byrne, Henry D. Tazelaar, John S. Logan, Christopher G.A. McGregor

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Background: Microvascular thrombosis is a prominent characteristic of delayed xenograft rejection, therefore the effects of antiplatelet therapy with aspirin and clopidogrel on long-term cardiac xenograft function was investigated in a heterotopic pig-to-baboon cardiac transplant model. Methods: Donor hearts from human CD46 transgenic pigs were transplanted heterotopically to baboons. The recipients received immunosuppression that included tacrolimus, sirolimus, corticosteroids, anti-CD20 monoclonal antibody and TPC, an α-galactosyl- polyethylene glycol conjugate. In group 1 (n = 9) in addition to immunosuppression, the recipients received combination therapy consisting of aspirin (80 mg/day) and clopidogrel (75 mg/day) beginning 2 days after transplant and continuing until cessation of graft function. Antiaggregatory efficacy was evaluated by platelet aggregation assay. In group 2 (n = 9) antiplatelet drugs were not given. Results: Functional assays confirmed inhibition of platelet aggregation in group 1 suggesting sufficient systemic effects of the treatment. However, anticoagulant therapy did not result in significant prolongation of xenograft function (group 1: median survival 22 days, range 15 to 30 days; group 2: median survival 15 days, range 4 to 53 days). Histologic analysis at rejection revealed no difference in the level of platelet containing thrombi between the groups. Conclusions: Inhibition of platelet aggregation by a combination of aspirin and clopidogrel did not have a significant impact on the length of xenograft survival or on the development of microvascular thrombosis in this pig-to-primate model.

Original languageEnglish (US)
Pages (from-to)436-443
Number of pages8
JournalXenotransplantation
Volume11
Issue number5
DOIs
StatePublished - Sep 1 2004

Keywords

  • Acute vascular rejection
  • Antiplatelet
  • Aspirin
  • Clopidogrel
  • Xenotransplant

ASJC Scopus subject areas

  • Immunology
  • Transplantation

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    Schirmer, J. M., Fass, D. N., Byrne, G. W., Tazelaar, H. D., Logan, J. S., & McGregor, C. G. A. (2004). Effective antiplatelet therapy does not prolong transgenic pig to baboon cardiac xenograft survival. Xenotransplantation, 11(5), 436-443. https://doi.org/10.1111/j.1399-3089.2004.00159.x