Nuclear magnetic resonance (NMR) criteria of early cardiac rejection are similar to those seen in myocardial ischemia, that is, a reduction of high energy phosphatases (Pc; ATP) and an increase of inorganic phosphates (Pi). Our aim was to assess in vivo changes of phosphorous spectroscopy (31P) induced by cardiac rejection and myocardial ischemia in the same animal. Heterotopic heart isografts (n = 5) and untreated allografts (n = 5) were examined at seven days on a two tesla wide-bore magnet with a surface coil. Subtotal global ischemia was produced for sequential NMR measurements, followed by heart excision for histological rejection grading (Billingham). Results 1. Isograft served as controls and showed normal energy-rich phosphate compounds and pH. 2. Rejecting (moderate to severe) allografts showed a decrease of Pc/Pi and beta-ATP/Pi ratio compared with isografts. However no significant pH drop could be detected. 3. Induced ischemia was confirmed by marked ECG-ST elevation and showed a significant early global myocardial acidosis (pH less than 6.9) particularly in severe prolonged ischemia (p less than 0.05). 4. Using 31P NMR techniques, ischemically induced changes were similar in isografts and allografts with a trend towards a more pronounced extent in the latter groups. In conclusion, magnetic resonance spectroscopy (31P and pH) allows in vivo differentiation between cardiac rejection and acute myocardial ischemia.

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We assessed FK506 (FK) 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 histologic grading of rejection (Billingham and working formulation) at 1 week. Two doses of FK (2.0 and 8.0mg/kg p.o., q.d.) and RPM (1.5 and 6.0mg/kg i.p., q.d.) were compared to allografts without and with ciclosporin (12.5mg/kg p.o., q.d.) treatment. Results show: (1) weak heartbeat and full rejection on day 5 in all untreated allografts; (2) weak heartbeat and high degree of rejection in groups receiving low doses of FK and RPM; (3) strong heartbeat and mild rejection in both high FK and RPM dose groups comparable to the results of the hearts treated with ciclosporin; (4) 1 animal in each high FK and RPM dose group showed possible signs of toxicity, and (5) the strength of the heartbeat was not a reliable indicator of the efficacy of an immunosuppressive drug. We conclude that even in a major histocompatibility mismatch model at the time of the strongest immune response (1 week), all three tested drugs can reduce the degree of rejection from severe (untreated allografts) to mild if given in an adequate dosage.

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.

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 31 P 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 mglkg 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.