Molecular forms of adrenomedullin in pericardial fluid and plasma in patients with ischaemic heart disease

Experimental studies have demonstrated that adrenomedullin (AM) has a positive inotropic action and exerts inhibitory effects against ventricular remodelling as an autocrine and paracrine factor. However, there is no clinical evidence for AM acting as a local regulator in the human heart. We measured the levels of various molecular forms of AM, i.e. an active form of mature AM (AM-m), an intermediate inactive form of glycine-extended AM (AM-Gly) and total AM (AM-T=AM-m+AM-Gly), in plasma and pericardial fluid using our newly developed immunoradiometric assay in consecutive 67 patients undergoing coronary artery bypass graft surgery. Pericardial fluid and plasma cAMP, atrial natriuretic peptide and brain natriuretic peptide levels were also measured. The relationships between pericardial fluid AM levels and ventricular functions and other hormone levels were analysed. The level of each molecular form of AM in pericardial fluid was closely correlated with that of the other molecular forms of AM in the fluid. However, levels were not correlated with those in plasma. AM-T levels were slightly higher in pericardial fluid than in plasma (+72%; P<0.05), whereas AM-m levels and AM-m/AM-T ratios were markedly higher in pericardial fluid than in plasma (AM-m, +994%; AM-m/AM-T ratio, +443%; both P<0.01). AM-m, AM-Gly and AM-T levels in pericardial fluid were correlated with indices of left ventricular function, and with atrial natriuretic peptide and brain natriuretic peptide levels. Interestingly, AM and cAMP levels were positively correlated in plasma, but negatively correlated in pericardial fluid. In addition, AM-m, AM-Gly and AM-T levels in pericardial fluid were higher in patients with acute coronary syndrome than in those with stable ischaemic heart disease (AM-m, +80%; AM-Gly, +96%; AM-T, +83%; all P<0.01). These results suggest that AM in pericardial fluid reflects cardiac synthesis, and that enhanced cardiac secretion of AM is associated with left ventricular dysfunction, ventricular overload and myocardial ischaemia. Considering that AM has positive inotropic, coronary vasodilatory and anti-remodelling actions, increased cardiac AM may play a compensatory role in the ischaemic and failing myocardium.     

Cardiometabolic therapy of ischemic heart disease

A total of 59 patients suffering from ischemic heart disease with effort angina (functional classes II-IV) entered the study. Of them, 29 patients received antianginal drugs and 10-day courses of a combination of drugs with membran-oprotective properties (MPD); 30 patients received antianginal drugs alone. Blood levels of lipid peroxidation products, lipid structure of erythrocytic membrane, exercise tolerance were studied before and after the treatment. MPD therapy was associated with lower activity of lipid peroxidation, stabilization of cell membrane structure and greater exercise tolerance due to more effective cardiac performance.     

Secondary prevention of ischemic heart disease

Thirty-three coronary patients received preventive therapy in unfavorable for the disease seasons (late autumn, early winter). Chemotherapy included three treatment combinations: acetylsalicylic acid plus nicotinic acid, curantyl plus nicotinic acid and intercordin plus potassium salts. The preventive measures reduced the frequency of anginal attacks and meteoropathic reactions. The hemostasis, fibrinolysis and microcirculation exhibited a positive trend.