Tacrolimus versus cyclosporine induction therapy in pulmonary transplantation in miniature swine.

Objective: Tacrotimus has been shown to provide superior immunosuppression in various solid organ transplant settings. The purpose of our study was to compare the survival of porcine lung allografts after induction with either cyclosporine A (CsA) or tacrolimus. Methods: Single lung transplantation from MHC mismatched donors was performed in 10 minipigs. Immunosuppression included 1.5mg/kg per day methylprednisotone and 1.0 mg/kg per day azathioprine. CsA (n = 5) was adjusted to trough levels of 300-500 ng/ml, tacrotimus (n- 5) was adjusted to 16-26 ng/ml. AU immunosuppressive drugs were discontinued on postoperative day (POD) 28. Allograft survival was monitored by sequential chest radiographs, bronchoscopy and transbronchial. biopsy histology. Peripheral blood leukocytes were scanned for donor chinnerism and CD3, CD4, CD8 and CD25 expression. Results: The animals survived a 4-week course of immunosuppression without radiological or histological signs of rejection on POD 28. Median attograft survival in CsA-treated animals was 55 +/- 15 days and aR animals rejected their grafts within 42 days after withdrawal of immunosuppression. In tacrotimus-treated animals, median survival was 152 +/- 65 days with the longest survivor being electively sacrificed on POD 390 (P=0.0064). Thedegreeof donor leukocyte chimerism and thefrequencyof CD4(+)CD25(+)T-cells were higher in the tacrolimus group, however, these differences were not statistically significant. Conclusion: Theresultsof our study show that primary immunosuppression with tacrotimus is superior to cyclosporine after pulmonary allotransplantation in a large animal model. (c) 2005 Elsevier B.V. Alt rights reserved.