Life supporting function for over one month of a transgenic porcine heart in a baboon

Background: Inhibition of hyperacute rejection (HAR) and sustained graft su rvival have been demonstrated in a pig-to-primate model of heterotopic card iac xenotransplantation using pigs transgenic for human Decay Accelerating Factor (hDAF). Building on this work, an orthotopic model has been develope d. This case records 39-day cardiac xenograft function in a life-supporting capacity with clinically applicable immunosuppression. Methods: Using a heart from an hDAF transgenic pig, an orthotopic cardiac t ransplant was performed on an adult baboon. The immunosuppressive regimen c onsisted of induction with a short course of cyclophosphamide, followed by maintenance therapy with cyclosporine A, mycophenolate mofetil and a taperi ng course of corticosteroids. Post-operative monitoring included daily anti -pig hemolytic antibody titer surveillance and endomyocardial biopsy. Results: The animal survived 39 days and was active and energetic throughou t its postoperative course, remaining free of signs of cardiopulmonary fail ure. Endomyocardial biopsy performed on post-operative Day 36 revealed only patches of sub-endocardial fibrosis with no signs of active rejection. The baboon succumbed to an acute cardiopulmonary decompensation immediately fo llowing administration of medication via oral gavage. Post-mortem histopath ology demonstrated well-preserved myocardial architecture with small foci o f mild humoral rejection. Conclusions: This case documents the longest survival recorded to date of a discordant orthotopic cardiac xenograft and illustrates that the hDAF tran sgene combined with a clinically acceptable maintenance immunosuppressive r egimen enables sustained, life-supporting function of porcine cardiac xenog rafts in non-human primates. The inhibition of hyperacute rejection and the subsequent control of humoral and cellular rejection for over 1 month demo nstrated in this experiment represent significant progress in the developme nt of a viable strategy for clinical xenotransplantation.