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J Thorac Cardiovasc Surg 2000;120:29-38
© 2000 The American Association for Thoracic Surgery
CARDIOTHORACIC TRANSPLANTATION |
From the Department of Surgery,a Duke University Medical Center, Durham, NC; the Departments of Surgery, Pediatrics, and Immunology,c Mayo Foundation, Rochester, Minn; and Nextran,b Princeton Forrestal Center, Princeton, NJ.
Supported by National Institutes of Health grants HL50985 and HL52297 and by Nextran. Christine L. Lau is a recipient of the International Society for Heart and Lung Transplantation Research Fellowship.
Address for reprints: R. Duane Davis, MD, Department of General and Thoracic Surgery, Box 3864, Duke University Medical Center, Durham, NC 27710 (E-mail: davis053{at}mc.duke.edu ).
Objective: Pulmonary transplantation has become the preferred treatment for end-stage lung disease, but application of the procedure is limited because of a paucity of donors. One way to solve donor limitations is to use animal organs as a donor source or xenotransplantation. The current barrier to pulmonary xenotransplantation is the rapid failure of the pulmonary xenograft. Although antibodies are known to play a role in heart and kidney xenograft rejection, their involvement in lung dysfunction is less defined. This project was designed to define the role of antibodies in pulmonary graft rejection in a pig-to-baboon model.
Methods: Orthotopic transgenic swine left lung transplants were performed in baboons depleted of antibodies by one of three techniques before transplantation: (1) ex vivo swine kidney perfusion, (2) total immunoglobulin-depleting column perfusion, and (3) ex vivo swine lung perfusion. Results were compared with those of transgenic swine lung transplants in unmodified baboons.
Results: All three techniques of antibody removal resulted in depletion of xenoreactive antibodies. Only pretransplantation lung perfusion improved pulmonary xenograft function compared with lung transplantation in unmodified baboons.
Conclusions: The pathogenesis of pulmonary injury in a swine-to-primate transplant model is different from that in renal and cardiac xenografts. Depletion of antibodies alone does not have a beneficial effect and may actually be detrimental.
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