Life-supporting pig-to-baboon heart xenotransplantation

Background: The aim of this study was to investigate the effect of the expr ession of human decay-accelerating factor in transgenic pigs on hyperacute rejection in a pig-to-baboon heterotopic heart transplantation model and to assess the ability of such transgenic pig hearts in supporting the life of a primate when transplanted orthotopically. Methods: Hearts from pigs transgenic for human decay-accelerating factor we re transplanted heterotopically (n = 3) and orthotopically (n = 5) into the baboon. All animals received cyclosporine, steroids, and cyclophosphamide. Blood was sampled regularly for total antipig antibody titers, trough cycl osporine levels, full blood count, electrolytes, and creatinine. Rejection of the heterotopic hearts was defined as the absence of palpable cardiac pu lsation. Explanted hearts were examined histologically with hematoxylin and eosin and with immunochemistry for complement components C3, C4, C9, and i mmunoglobulin M. Results: None of the hearts were hyperacutely rejected. In the heterotopic group one heart underwent acute vascular rejection on day 13, and the remai ning two recipients with beating xenografts were killed on days 2 and 21. I n the orthotopic group, one recipient with a life-supporting xenograft was killed on day 9 because of poor general condition. Histologic examination d emonstrated no evidence of rejection. Two xenografts stopped beating on day 5, and histologic study showed acute vascular rejection in both. There wer e also two graft failures for technical reasons in this group. Conclusions: Hyperacute rejection is abrogated in pig-to-baboon heart xenot ransplantation with the expression of the human decay-accelerating factor t ransgene. The human decay-accelerating factor transgenic pig heart is able to support primate Life for a prolonged period.