Prolongation of Heterotopic Rat Heart Allograft Survival by ‘Methotrexate-Folinic Acid Rescue

Brown Norway rats received heterotopic (WF/BN) X F1 heart transplants. Functional graft survival time (FST) was 10.0 ± 0.5 days. When the highest tolerable daily dose of methotrexate (25 µg/kg) was given, FST was 26.2 ± 5.6 days. When the highest tolerable dose of methotrexate with ‘folinic acid rescue’ (175 µg/kg) was administered, the FST was found to be 25.3 ± 11.0 days. Folinic acid given between daily methotrexate doses diminished the toxicity of the latter drug but also its therapeutic transplant-protective effectiveness. Methotrexate alone given in multiple nontoxic doses proved to be a strong and safe transplant-protective immunosuppressive agent.