Tacrolimus versus cyclosporine induction therapy in pulmonary transplantation in miniature swine.
OBJECTIVE
Tacrolimus 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 1.5 mg/kg per day methylprednisolone and 1.0 mg/kg per day azathioprine. CsA (n=5) was adjusted to trough levels of 300-500 ng/ml, tacrolimus (n=5) was adjusted to 16-26 ng/ml. All 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 chimerism 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 allograft survival in CsA-treated animals was 55+/-15 days and all animals rejected their grafts within 42 days after withdrawal of immunosuppression. In tacrolimus-treated animals, median survival was 152+/-65 days with the longest survivor being electively sacrificed on POD 390 (P=0.0064). The degree of donor leukocyte chimerism and the frequency of CD4+CD25+ T-cells were higher in the tacrolimus group, however, these differences were not statistically significant.


CONCLUSIONS
The results of our study show that primary immunosuppression with tacrolimus is superior to cyclosporine after pulmonary allotransplantation in a large animal model.
Warnecke
Gregor
G
Division of Thoracic and Cardiovascular Surgery, Hannover Medical School, Carl-Neuberg-Strasse 1, 30623 Hannover, Germany.
Avsar
Murat
M
Steinkamp
Thomas
T
Reinhard
Renate
R
Niedermeyer
Jost
J
Simon
André R
AR
Haverich
Axel
A
Strüber
Martin
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002678:Chimera; D016572:Cyclosporine / Q000627:therapeutic use*; D005434:Flow Cytometry; D006085:Graft Survival; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007962:Leukocytes / Q000276:immunology; D008171:Lung Diseases / Q000276:immunology / Q000601:surgery*; D016040:Lung Transplantation / Q000379:methods*; D007959:Lymphocyte Culture Test, Mixed; D023421:Models, Animal; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013552:Swine; D013556:Swine, Miniature; D016559:Tacrolimus / Q000627:therapeutic use*; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D016572:Cyclosporine; D016559:Tacrolimus