Circulating adrenomedullin is increased after heart transplantation

Objective: Adrenomedullin (ADM), secreted by the failing human heart, is a newly discovered potent endogenous vasorelaxing and natriuretic peptide that may play a role in cardiorenal regulation. No data are available on ADM in heart-transplant recipients (Htx) and the aim of this study was to determine the short- and long-term responses of ADM after heart transplantation. Methods: Circulating ADM and its relationship with parameters of cardiovascular hemodynamics, humoral factors and renal function were determined in normal subjects and Htx early (1, 2, 4, 8, 15 and 30 days) and late (32±16 months) after transplantation. Additionally, ADM was obtained in matched hypertensive and renal-transplant patients (n=9 in each group). Results: Plasma ADM, elevated in heart failure patients, further increased transiently at day 1 after transplantation (from 37.9±15.9 to 125.8±15.3 pmol/1, P<0.01) and, although decreasing thereafter, remained elevated until the 30th day after transplantation (52.1±25.2 pmol/1). Late after transplantation, ADM concentrations were still increased compared to normal values (31.3±5.3 vs, 19.4±2.7 pmol/1, P<0.001). ADM positively correlated with endothelin, atrial natriuretic peptide (ANP) and cyclosporine. ADM was also correlated with increased diastolic (r=0.68, P<0.04) and systolic (r=0.66, P<0.05) blood pressure in late Htx. No relationship was observed between ADM and left ventricular mass index, aldosterone and creatinine. ADM elevation was similar in hypertensive, renal- transplant patients and in Htx. Conclusions: Circulating ADM is increased after heart transplantation, in relation to hypertension, endothelin, cyclosporine and ANP. In view of ADM'S biological properties, these results might suggest a compensatory role for ADM against further development of vasoconstriction and fluid retention states after heart transplantation.