CARDIAC SECRETION OF ADRENOMEDULLIN IN HUMAN HEART-FAILURE

Adrenomedullin (ADM) is a newly discovered endogenous vasorelaxing and natriuretic peptide. Recently, we have reported that plasma ADM is in creased in severe congestive heart failure (CHF) in humans and that in creased immuno-histochemical staining is observed in the failing human ventricular myocardium. The present study was designed to test the hy pothesis that the failing human ventricle secretes ADM and that circul ating ADM progressively increases with the severity of clinical CHF, P lasma ADM was significantly increased in human CHF (39.8 +/- 3.6 pg/ml , P < 0.001 vs. normal) as compared with normal subjects (14.4 +/- 2.7 pg/ml), Plasma ADM was increased in mild CHF (NYHA class II, 30.1 +/- 3.4 pg/ml, P < 0.01 vs. normal), moderate CHF (NYHA class III, 31.5 /- 3.0 pg/ml, P < 0.01 vs. normal), and severe CHF (NYHA class IV, 66. 1 +/- 9.4 pg/ml, P < 0.001 vs. normal). In 13 patients with CHF in who m plasma samples were obtained from aorta (AO), coronary sinus (CS) an d anterior interventricular vein (AIV), there was a significant step-u p in plasma ADM between AO and AIV (50.6 +/- 9.3 pg/ml and 62.1 +/- 11 .1 pg/ml, respectively, P < 0.01) and between AO and CS (50.6 +/- 9.3 pg/ml and 58.6 +/- 11.4 pg/ml, respectively, P < 0.05). The current st udy demonstrates that the failing human heart secretes ADM in human CH F suggesting contribution to the increase in plasma ADM, and indicates for the first time an additional endocrine system of cardiac origin w hich is activated in human CHF and may function in cardiorenal regulat ion. (J. Clin. Invest. 1996. 97: 2370-2376.)