Molecular forms of circulating adrenomedullin in patients with congestive heart failure

In the biosynthesis of adrenomedullin (AM), an intermediate form, AM(1-52)- glycine-COOH (iAM), is cleaved from proAM and subsequently processed to a b iologically active mature form, AM(1-52)-NH2 (mAM), by enzymatic amidation. We recently reported that immunoreactive AM in human plasma consists of mA M and iAM. To clarify the pathophysiological roles of mAM and iAM in heart failure, we established an assay method to specifically detect mAM, and we determined the plasma concentrations of mAM and iAM in 68 patients with con gestive heart failure (CHF). The plasma mAM concentrations of the CHF patie nts classified as being class I or II of New York Heart Association (NYHA) functional classification were significantly greater than those of the 28 h ealthy controls, and a further increase was noted in the class III or IV pa tients. Similar increases in plasma iAM were also observed in these patient s compared with controls. The increased plasma mAM and iAM in 12 patients w ith exacerbated CHF were significantly reduced by treatment of their CHF fo r 7 days. In addition, the plasma concentrations of both mAM and iAM were s ignificantly correlated with pulmonary capillary wedge pressure, pulmonary artery pressure, right atrial pressure, cardiothoracic ratio, heart rate, a nd the plasma concentrations of atrial and brain natriuretic peptides in th e CHF patients. Thus the plasma concentrations of both mAM and iAM were inc reased progressively in proportion to the severity of CHF. These results su ggest that, though the role of iAM remains to be clarified, mAM acts agains t the further deterioration of heart failure in patients with CHF.