Prevention of cardiac allograft rejection by FK506 and rapamycin: assessment by histology and nuclear magnetic resonance

Abstract

We assessed the effect of FK506 and rapamycin (RPM) in a heterotopic abdominal rat heart transplant model using a major histocompatibility mismatch (DA to LEW). The end-point of our study was the histologic grading of rejection (Stanford) and 31P magnetic resonance spectroscopy (MRS) at 1 week after transplantation. Two dosages of FK506 (2.0 and 8.0 mg/kg per os daily) and RPM (1.5 and 6.0 mg/kg intraperitoneally daily) were compared in allografts without and with cyclosporine (12.5 mg/kg per os daily) treatment. The results show: Weak heartbeat and full rejection at day 5 in all untreated allografts; severe rejection in groups on a low dose of FK506 and RPM; mild rejection in both high dose groups comparable to the results of the hearts treated with cyclosporine; MRS does not allow differentiation between no or mild forms of rejection. Energy-rich phosphates are near normal in the high dosage immunosuppression groups but show a significant reduction in the low dosage groups. We conclude that all three tested drugs can reduce the degree of rejection from severe (untreated allografts) to mild if given in an adequate dosage. MRS correlates well with the degree of histologic rejection but permits only the diagnosis of moderate or severe rejection.