Elevation of two molecular forms of adrenomedullin in plasma and urine in patients with acute myocardial infarction treated with early coronary angioplasty

Abstract

Adrenomedullin (AM) has vasodilatory, diuretic and natriuretic actions. Two molecular forms of AM circulate in human plasma: an active, mature form of AM (AM-m) and an intermediate, inactive, glycine-extended form of AM (AM-Gly). In the present study we investigated the pathophysiological significance of the two molecular forms of AM in plasma and urine in patients with acute myocardial infarction. We serially measured venous and arterial plasma levels and urinary excretion of AM-m, AM-Gly and total AM (Am-T; =AM-m+AM-Gly) over 2 weeks using our recently developed immunoradiometric assay in 26 consecutive patients with acute myocardial infarction and in age-matched normal controls, and studied the relationships between AM levels and clinical parameters. Plasma AM-m, AM-Gly and AM-T levels were increased on admission in patients with acute myocardial infarction compared with age-matched normal controls. Levels of AM-m, AM-Gly and AM-T in plasma reached a peak 24 h after the onset of symptoms. Plasma AM-m, AM-Gly and AM-T levels were significantly correlated with plasma levels of brain natriuretic peptide and pulmonary arterial pressure. Plasma AM-Gly levels in the vein were similar to those in the artery, whereas plasma AM-m levels were significantly lower in the artery than in the vein. Urinary excretion of AM-m, AM-Gly and AM-T was also increased on admission, and reached a peak at 12 h after the onset of symptoms. Urinary excretion of AM-m and AM-Gly was significantly correlated with urinary sodium excretion. The AM-m/AM-T ratio was significantly higher in the urine than in the vein or artery. AM-m levels were significantly correlated with AM-Gly levels in both the urine and plasma; however, there were no significant correlations between plasma and urinary AM levels. The results suggest that levels of both molecular forms of AM are increased in the urine as well as in the plasma in the acute phase of myocardial infarction. Since AM exerts potent cardiovascular and renal effects, increased concentrations of AM in plasma and urine in the acute phase of myocardial infarction may be involved in the defence mechanism against further elevations of peripheral and pulmonary vascular resistance and oliguria in acute myocardial infarction.

Cardiovascular Alterations Associated with Acute Pancreatitis

“…Isolated in human pheochromocytoma, it is also present in the heart, brain, lung, kidney and gastrointestinal organs, and elicits its potent vasodilatory activity through an increase in cyclic adenosine monophosphate levels. Plasma concentrations of ADM are increased in patients with myocardial infarction [19] and correlate with the severity of congestive heart failure. The reliable quantification of ADM is hindered by a short half-life and technical difficulties.…”

Copeptin, myeloperoxidase and pro-adrenomedullin for acute coronary syndrome in patients with chronic kidney disease

“…[60][61][62] While it has not been shown to have utility in the early diagnosis of myocardial infarction, it may be prognostic of adverse outcomes and all-cause mortality among patients presenting with acute chest pain. 31,63 Elevated levels are seen in other cardiovascular conditions, including congestive heart failure 64,65 and hypertension, 66 as well as noncardiovascular conditions such as systemic inflammatory states 67 and type 2 diabetes mellitus. 68 Once again, increased levels seen in patients with CKD 69,70 further confound its interpretation in the setting of ACS, reducing its relevance for clinical use.…”

Heart in acute pancreatitis: facts and fictions

“…Finally, adrenomedullin (ADM), a 52-amino-acid peptide elevated in plasma of patients having heart failure and/or postacute coronary syndrome, has been isolated in human pheochromocytoma and it is also present in the heart, brain, lung, kidney and gastrointestinal organs; it has a potent vasodilator activity due to an increase in cyclic adenosine monophosphate levels. 27 It should be underlined that the quantification of ADM is quite difficult due to a short halflife and the lack of the reliable laboratory techniques. The identification of mid-regional pro-adrenomedullin (MR-proADM) 28,29 has overcome these problems, because it is a stable peptide possibly reflecting the concentration of ADM. MR-proADM is probably secreted in equimolar amounts to those of ADM, and it does not have any physiological effects which might explain its apparent stability.…”