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 hyperacutely 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, transgenic 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 histological signs of hyperacute rejection. Pulmonary artery thrombosis induced by a size mismatch was observed in two of these animals. The other three recipients died because of failure to produce even a low cardiac output and/or dysrhythmia. The remaining five animals survived between four and nine days. One animal died of bronchopneumonia on day 4. Three xenografts stopped beating on day 5 due to acute vascular rejection. The longest survivor was killed on day 9 with a beating, histologically 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. Orthotopically transplanted transgenic pig hearts are capable of maintaining cardiac output in baboons. An optimum immunosuppressive regimen is the subject of ongoing research.
Imutran Ltd./A Novartis Pharma AG Company, Department of Cardiothoracic Surgery, Papworth Hospital, Cambridge, United Kingdom.
M
M
Schmoeckel
F N
FN
Bhatti
A
A
Zaidi
E
E
Cozzi
P D
PD
Waterworth
M J
MJ
Tolan
G
G
Pino-Chavez
M
M
Goddard
R G
RG
Warner
G A
GA
Langford
J J
JJ
Dunning
J
J
Wallwork
D J
DJ
White
D000818:Animals; D030801:Animals, Genetically Modified; D018958:CD55 Antigens / Q000235:genetics / Q000502:physiology*; D005260:Female; D006084:Graft Rejection; D016027:Heart Transplantation; D007165:Immunosuppression Therapy; D008297:Male; D010215:Papio; D013552:Swine; D014183:Transplantation, Heterologous
D018958:CD55 Antigens