ORTHOTOPIC HEART-TRANSPLANTATION IN A TRANSGENIC PIG-TO-PRIMATE MODEL

Background. Previous studies demonstrated that hearts from transgenic pigs expressing human decay-accelerating factor (hDAF) were not hypera cutely rejected when transplanted heterotopically into the abdomen of cynomolgus monkeys. This study examines orthotopic transplantation of hDAF transgenic pig hearts into baboon recipients, Methods. Orthotopic xenogeneic heart transplantation was performed using piglets, transge nic for hDAF, as donors. Ten baboons were used as recipients and were immunosuppressed with a combination of cyclophosphamide, cyclosporine, and steroids, Results, Five grafts failed within 18 hr without any hi stological signs of hyperacute rejection. Pulmonary artery thrombosis induced by a size mismatch was observed in two of these animals. The o ther three recipients died because of failure to produce even a low ca rdiac output and/or dysrhythmia. The remaining five animals survived b etween four and nine days, One animal died of bronchopneumonia on day 4. Three xenografts stopped beating on day 5 due to acute vascular rej ection, The longest survivor was killed on day 9 with a beating, histo logically normal xenograft, because of pancytopenia. Conclusions. The results reported here demonstrate that hDAF transgenic pig hearts are not hyperacutely rejected when transplanted into baboon recipients. Or thotopically transplanted transgenic pig hearts are capable of maintai ning cardiac output in baboons. An optimum immunosuppressive regimen i s the subject of ongoing research.