INCREASED CIRCULATING ADRENOMEDULLIN, A NOVEL VASODILATORY PEPTIDE, IN SEPSIS

Human adrenomedullin (hAM), a potent vasodilatory peptide originally i dentified in pheochromocytoma, has been shown to be present in various human tissues and circulate in human plasma. We measured plasma conce ntrations of immunoreactive hAM in patients with sepsis who had been a dmitted to intensive care unit (ICU). Plasma hAM concentrations in 12 septic patients upon entering the ICU were extremely elevated (107 +/- 139 fmol/ml: mean +/- SD) compared to those of 16 age-matched normal subjects (7.9 +/- 3 fmol/mL). Among 10 patients with normal renal func tion, plasma hAM levels either decreased or increased during the hospi tal course; the former group survived and the latter group succumbed. Two patients with acute renal failure had markedly elevated plasma hAM levels during the early course, which declined rapidly during the rec overy course. High performance liquid chromatography of plasma extract s from one patient with acute renal failure revealed a single major co mponent of immunoreactive hAM coeluting with authentic hAM (1-52) duri ng acute and recovery phase. Plasma hAM concentration showed positive correlations with heart rate, right atrial pressure, and serum creatin ine concentration, but not with other hemodynamic variables. These dat a suggest that a marked increase in circulating hAM in sepsis may be c aused by its decreased clearance and/or its enhanced synthesis by mult iple organ dysfunction, and that increased endogenous hAM may be invol ved in the mechanism of cardiovascular abnormalities associated with s epsis.