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

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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 2004

Fingerprint

clopidogrel
Papio
Heterografts
Swine
Platelet Aggregation
Aspirin
Thrombosis
Transplants
Immunosuppression
Survival
Platelet Aggregation Inhibitors
Tacrolimus
Sirolimus
Therapeutics
Anticoagulants
Primates
Adrenal Cortex Hormones
Blood Platelets
Monoclonal Antibodies

Keywords

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

ASJC Scopus subject areas

  • Immunology

Cite this

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

Effective antiplatelet therapy does not prolong transgenic pig to baboon cardiac xenograft survival. / Schirmer, Johannes M.; Fass, David N.; Byrne, Guerard W.; Tazelaar, Henry D.; Logan, John S.; McGregor, Christopher G A.

In: Xenotransplantation, Vol. 11, No. 5, 09.2004, p. 436-443.

Research output: Contribution to journalArticle

Schirmer, JM, Fass, DN, Byrne, GW, Tazelaar, HD, Logan, JS & McGregor, CGA 2004, 'Effective antiplatelet therapy does not prolong transgenic pig to baboon cardiac xenograft survival', Xenotransplantation, vol. 11, no. 5, pp. 436-443. https://doi.org/10.1111/j.1399-3089.2004.00159.x
Schirmer, Johannes M. ; Fass, David N. ; Byrne, Guerard W. ; Tazelaar, Henry D. ; Logan, John S. ; McGregor, Christopher G A. / Effective antiplatelet therapy does not prolong transgenic pig to baboon cardiac xenograft survival. In: Xenotransplantation. 2004 ; Vol. 11, No. 5. pp. 436-443.
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