Baboons undergoing orthotopic concordant cardiac xenotransplantation surviving more than 300 days: Effect of immunosuppressive regimen

Miki Asano, Steven R. Gundry, Hironori Izutani, Sandra Nehlsen Cannarella, Omar Fagoaga, Leonard L. Bailey, Robert E. Michler

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Objective: We reviewed long-term survival among hosts in 3 consecutive series of a rhesus monkey-baboon orthotopic cardiac xenotransplantation model with reference to host immune response, including the effectiveness in preventing rejection and limiting toxicity concerning infection, to evaluate specific immunosuppressive regimens for long-term outcomes. Methods: Six juvenile baboons surviving more than 300 days after transplantation were reviewed. Regimen A consisted of splenectomy, FK506, methotrexate, and antilymphocyte globulin. Regimen B consisted of pretransplantation and chronic maintenance with cyclosporine A (INN: ciclosporin), methotrexate, and antithymocyte globulin. Regimen C was the same as regimen B plus pretransplantation total lymphoid irradiation and intraoperative donor bone marrow cell infusion. Rejections were detected by means of echocardiography. Results: Long-term survivors in 3 groups were followed for a range of 332 to 515 days (mean, 436 days). Rejection frequency in regimens A, B, and C was 0.35, 0.58, and 0.18 per month, and rescue therapy days were 23 (4.8%), 123 (9.5%), and 20 (2.4%), respectively (P < .0001). Infection frequency was 0.58, 0.56, and 0.19 per month, and therapy days were 192 (38.2%), 164 (12.6%), and 7 (0.9%), respectively (P < .0001). Concerning the host immune response, interleukiri 2-activated T cells of all groups during rejection-free periods showed lower numbers compared with those of control animals (P < .0005), and regimen C was the lowest among 3 groups (P < .01). The production of xenoantibody was sufficiently attenuated in all groups. Conclusion: Regimen C leads to long-term survival with fewer rejection and infection episodes by means of suppression of the interleukin 2 pathway and xenoantibody production.

Original languageEnglish (US)
Pages (from-to)60-70
Number of pages11
JournalJournal of Thoracic and Cardiovascular Surgery
Volume125
Issue number1
DOIs
StatePublished - Jan 1 2003

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ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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