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J Thorac Cardiovasc Surg 2005;130:844
© 2005 The American Association for Thoracic Surgery

Cardiothoracic Transplantation

Cardiac xenotransplantation: Recent preclinical progress with 3-month median survival

Division of Cardiovascular Surgery, Department of Surgery, Mayo Clinic, and the Mayo Clinic William J. von Liebig Transplant Center, Rochester, Minn.

Received for publication February 24, 2005; revisions received April 7, 2005; accepted for publication April 7, 2005.

^_* Address for reprints: Christopher G. A. McGregor, MB, FRCS, Director, Mayo Clinic William J von Liebig Transplant Center, 6-716 Mary Brigh D, Saint Marys Hospital, Rochester, MN 55905. (Email: mcgregor.christopher{at}mayo.edu).

OBJECTIVES: Transplantation is limited by a lack of human organ donors. Organs derived from animals, most likely the pig, represent a potential solution to this problem. For the heart, 90-day median graft survival of life-supporting pig hearts transplanted to nonhuman primates has been considered a reasonable standard for entry into the clinical arena. Overcoming the immune barrier to successful cardiac xenotransplantation is most appropriately first explored with the non–life-supporting heterotopic model.

METHODS: We performed a series of 7 heterotopic heart transplantations from CD46 transgenic pigs to baboons using a combination of therapeutic agents largely targeted at controlling the synthesis of anti-pig antibodies. Rituximab (anti-CD20) and Thymoglobulin (rabbit antithymocyte globulin [ATG]; SangStat Medical Corp, Fremont, Calif) were used as induction therapy. Baseline immunosuppression consisted of splenectomy, tacrolimus, sirolimus, steroids, and TPC (an anti-Gal antibody therapeutic). Rejection events were not treated.

RESULTS: By using Kaplan-Meier analysis, median graft survival was 96 days (range, 15–137 days; 95% confidence interval, 38–99 days). Only 2 grafts were lost as a result of rejection, as defined by cessation of graft palpation. There was no evidence of a consumptive coagulopathy, infectious complications were treatable, and no posttransplantation lymphoproliferative disorders occurred. No cellular infiltration was observed.

CONCLUSIONS: This study reports the longest median survival to date (96 days) of pig hearts transplanted heterotopically into baboons. Duplication of these results in the orthotopic life-supporting position could bring cardiac xenotransplantation to the threshold of clinical application.

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