PROLONGED SURVIVAL OF HAMSTER-TO-RAT PULMONARY XENOGRAFTS BY TACROLIMUS (FK506) AND CYCLOPHOSPHAMIDE

Background: Severe shortage of donor organs in clinical lung transplan tation prompted us to investigate the potential use of pulmonary xenog rafts. The purpose of this study was to determine whether an immunosup pressive regimen of tacrolimus (FK506) and cyclophosphamide would prol ong the survival of hamster-to-rat pulmonary xenografts. Method: Left lung transplantation was done with male Golden Syrian hamsters used as donors and inbred male Lewis rats as recipients. Control animals (n = 10) received no immunosuppressive drugs whereas experimental animals (n = 6) were treated with tacrolimus and cyclophosphamide. Tacrolimus was administered intramuscularly at a dosage of 2 mg/kg per day on pos toperative days 0 to 4, followed by 1 mg/kg per day on days 5 to 29 an d 0.5 mg/kg per day on days 30 to 99. Cyclophosphamide (8 mg/kg per da y) was administered orally from the day before transplantation to day 8. After transplantation the animals were monitored by chest radiograp hy. Recipient animals were killed at timed intervals (days 60 and 100) and when the chest radiograph showed complete opacification of the tr ansplanted lung. At necropsy, pulmonary xenografts were examined histo logically for evidence of rejection, which was graded on a scale of 0 (no rejection) to 4 (severe rejection). Antihamster lymphocytotoxic an tibody titer was also measured in recipient animals after transplantat ion. Results: Pulmonary xenografts in the control animals had a medium survival time of 3 days, whereas the median survival in treated anima ls was more than 74 days. All pulmonary xenografts in control animals had severe rejection on day 3 after transplantation, whereas those in the treated animals had no rejection on days 60 and 100. The lymhocyto toxic antibody titers in control animals increased from 1:16 before op eration to 1:4096 on day 3 (p < 0.01). In the treated animals, the lym phocytotoxic antibody titer on day 21 was 1:8, which was not different from the preoperative value (1:16). Conclusion: These results indicat e that a combination of tacrolimus and a short course of cyclophospham ide prolongs the survival of pulmonary xenografts in a hamster-to-rat model.