Rejection Pathways in Heart Transplant Recipients

Since the beginning of this century experimental heart transplantations in animal studies were performed.' These studies were started in Rotterdam in the seventies to compare heterotopic and orthotopic heart transplantations, and to study the process of chronic rejection. The history of the first human heart transplantation started in South-Africa and it was carried out by Barnard in 1967. Several cardiac surgeons around the world initiated new transplantation programmes. However, the problems with patient and donor organ selection as well as with immunosuppression, severe rejection and infection were common. This meant in 1968, only 22% of all transplants survived after the first year.6 Consequently, many centres stopped their programmes. Heart transplantation, as a routine treatment for organ failure, only became possible with the development in 1973 of the endomyocardial biopsy technique for monitoring acute rejection? and in 1975 by the further discovery of cyclosporin A. In the early eighties cyclosporin A was successfully introduced as an immunosuppressive medicine post clinical heart transplantation.' Cyclosporin A acts by binding to calmodulin and thereby inhibits the transcription of the IL-2 and IFN-y gene." With the development of these new processes, a 50% survival rate after 5 years was achieved in 1982.

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