Effective antiplatelet therapy does not prolong transgenic pig to baboon cardiac xenograft survival
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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: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Effective antiplatelet therapy does not prolong transgenic pig to baboon cardiac xenograft survival
AU - Schirmer, Johannes M
AU - Fass, David N
AU - Byrne, Guerard W
AU - Tazelaar, Henry D
AU - Logan, John S
AU - McGregor, Christopher G A
N1 - Copyright 2004 Blackwell Munksgaard
PY - 2004/9
Y1 - 2004/9
N2 - 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.
AB - 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.
KW - Animals
KW - Animals, Genetically Modified
KW - Antigens, CD/genetics
KW - Aspirin/pharmacology
KW - Clopidogrel
KW - Graft Rejection/immunology
KW - Graft Survival/drug effects
KW - Heart Transplantation/immunology
KW - Humans
KW - Membrane Cofactor Protein
KW - Membrane Glycoproteins/genetics
KW - Papio anubis
KW - Platelet Aggregation/drug effects
KW - Platelet Aggregation Inhibitors/pharmacology
KW - Swine
KW - Ticlopidine/analogs & derivatives
KW - Time Factors
KW - Transplantation, Heterologous/immunology
U2 - 10.1111/j.1399-3089.2004.00159.x
DO - 10.1111/j.1399-3089.2004.00159.x
M3 - SCORING: Journal article
C2 - 15303980
VL - 11
SP - 436
EP - 443
JO - XENOTRANSPLANTATION
JF - XENOTRANSPLANTATION
SN - 0908-665X
IS - 5
ER -
