Timing of antirejection therapy.

In order to determine the optimal time for treating rejection, groups of immunosuppressed rats bearing heart allografts were treated with single pulses of methylprednisolone on days 0, 2, 4, 6, or 8 after transplantation. Untreated rats rejected their grafts in 8 days. Treatment on day 0 prolonged the survival of the transplants in this group, but treatment on days 2 or 4 was largely ineffective. However, significant prolongation of graft survival was achieved when methylprednisolone was given on days 6 or 8. In a separate study, the electrical activity of nine heart allografts in immunosuppressed rats was recorded every 2nd day and biopsies were obtained on days 4, 6, and 8. These observations showed that rejection was well advanced on days 6 and 8, times when rejection treatment was most successful. In this model, therefore, it would seem that rejection treatment is more effective when given late (days 6 and 8) than when given early (days 2 and 4). Treatment on the day of transplantation (day 0) was also effective.