ELEVATION OF CIRCULATING AND VENTRICULAR ADRENOMEDULLIN IN HUMAN CONGESTIVE-HEART-FAILURE

Background Adrenomedullin (ADM) is a newly discovered vasodilating and natriuretic peptide that may play an important role in cardiorenal re gulation. Although ADM was originally isolated from human pheochromocy toma, ADM-like immunoreactivity has also been widely detected in vario us tissues, including the cardiovascular system. Methods and Results I n view of reports that ADM circulates in the body and that ADM gene an d ADM-like immunoreactivity are present in the heart, the present stud y was designed to determine the plasma concentration of ADM in healthy subjects and in patients with congestive heart failure (CHF) and to i nvestigate the immunohistochemical presence and localization of ADM in normal and failing human hearts. Plasma ADM concentration was 13.2+/- 2.3 pg/mL in healthy subjects (n=11) and increased to 47.3+/-6.7 pg/mL in patients with CHF (n=11, P<.05 versus normal). Human cardiac tissu es were obtained from five patients with end-stage CHF undergoing card iac transplantation. Five normal donor hearts that were used for cardi ac transplantation served as sources for normal atrial tissues. Normal ventricular myocardium was also obtained by endomyocardial biopsy fro m the right ventricles of these donor hearts immediately before cardia c transplantation. Positive immunostaining was detected within the myo cardia in both atria and ventricles of healthy and severely failing hu man transplanted hearts and was more intense in the atria than in the ventricles. Although there were no significant differences in the inte nsity of immunoreactivity between normal and failing atria, ADM immuno reactivity was significantly more intense in the ventricular myocytes from failing hearts compared with normal hearts. Conclusions The prese nt study demonstrates that plasma concentration of ADM is increased in patients with CHF and that ADM is present in the human heart. ADM imm unoreactivity is markedly increased in the failing human ventricle, su ggesting that ventricular ADM expression may be influenced by the circ umstances associated with CHF. This supports a potential role for this newly identified vasoactive and natriuretic peptide, ADM, in the neur ohumoral activation that characterizes human CHF.