Effective antiplatelet therapy does not prolong transgenic pig to baboon cardiac xenograft survival.
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 alpha-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.
Schirmer
Johannes M
JM
Mayo Clinic William J von Liebig Transplant Center, Mayo Clinic, Rochester, MN 55905, USA.
Fass
David N
DN
Byrne
Guerard W
GW
Tazelaar
Henry D
HD
Logan
John S
JS
McGregor
Christopher G A
CG
D000818:Animals; D030801:Animals, Genetically Modified; D015703:Antigens, CD / Q000235:genetics; D001241:Aspirin / Q000494:pharmacology; D000077144:Clopidogrel; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D006801:Humans; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000235:genetics; D048530:Papio anubis; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013552:Swine; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000473:pathology
D015703:Antigens, CD; C497857:CD46 protein, human; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin