Abstract
HEART transplantation is an established treatment for patients with end-stage heart failure. Optimal pharmacologic immunosuppression is needed to prevent morbidity and mortality associated with allograft rejection with a minimum of side effects associated with the immunosuppressive drug. Acute graft failure is a problem that apparently was overcome but, unfortunately, chronic rejection and the severe side effects of immunosuppressive drugs are the complications of organ transplantation which need a solution. Mycophenolate mofetil (MMF) is a new immunosuppressive drug with promising results, but long-term experience is still awaited. We have used MMF for more than 1.5 years in combination with cyclosporine A (CyA) and prednisone after cardiac transplantation. MMF is the morpholinethylester of the immunosuppressive agent mycophenolic acid (MPA). This new antimetabolite shows specific activity in lymphocytes where the target enzyme inosine monophosphate dehydrogenase (IMPDH) is blocked and therefore the production of guanosine triphosphate (GTP) inside the cell is reduced. In this way T and B lymphocytes are inhibited in differentiation and proliferation. The drug also reduces antibody production of plasma cells and production of GTP dependent ligands as endothelial adhesion molecules. MPA is glucuronidated to its single metabolite mycophenolic acid glucuronide (MPAG), which was shown to be immunosuppressive by itself. This new immunosuppressive drug is considered to have several advantages in comparison to azathioprine (AZA). Although there is a lot of experience with MMF in renal transplantation, scanty information is available in cardiac transplantation. This prospective, randomized study was designed to evaluate the clinical outcome of patients after heart transplantation under this novel regimen of immunosuppressive therapy and to reduce CyA whole-blood levels in the study group.
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