The effect of cyclosporin A on the level of big endothelin in patients one year after orthotopic heart transplantation.

Orthotopic heart transplantation (OHTx) is currently an established method for the treatment of end-stage heart failure. Persistent elevated plasma endothelin-1 (ET-1) levels have been reported after successful OHTx, the etiology of which is not yet fully understood. Immunosuppressive therapy is assumed to be one of the possible factors affecting ET-1 levels in the body. The present study evaluated the effect of cyclosporin A (CyA) on big ET-1 levels (a precursor of ET-1) in patients 1 year after successful OHTx. The study population comprised 34 patients after OHTx (28 males, 6 females, mean age 49.56+/-11.83 years) divided into two groups according to immunosuppressive protocol (17 patients on cyclosporine-azathioprine-prednisone and 17 patients on cyclosporine-mycophenolate mofetil-prednisone therapy). Plasma levels of big ET-1 and CyA were available for all patients. The control groups consisted of 10 healthy individuals (8 males, 2 females, mean age 41.1+/-11.55 years) and 20 patients with severe heart failure (15 males, 5 females, mean age 54.45+/-8.49 years), respectively. Big ET-1 plasma levels were found to be elevated in OHTx patients in comparison with healthy controls (13.63+/-11.3 fmol/ml vs 2.99+/-1.98 fmol/ml, P=0.005). Big ET-1 plasma levels correlated with plasma CyA levels in patients treated with cyclosporine-azathioprine-prednisone ( r=0.53, P=0.03). This was not the case in either in the OHTx patients as a whole or in the subgroup of patients on cyclosporine-mycophenolate mofetil-prednisone therapy. The plasma levels of big ET-1 are dependent on CyA plasma levels 1 year after successful OHTx in patients treated with the immunosuppressive combination of cyclosporine, azathioprine, and prednisone. As this finding was not observed in the mycophenolate group of patients, mycophenolate mofetil might affect the alteration of the endothelin metabolism.