Insufficient secretion of atrial natriuretic peptide at acute phase of myocardial infarction.

To investigate the secretion of the plasma levels of atrial natriuretic peptide (ANP) in patients with acute myocardial infarction (AMI), we evaluated the relationship between plasma levels of ANP and pulmonary capillary wedge pressure (PCWP) in 45 consecutive patients during the acute phase of AMI ( approximately 12 h after the attack) (group 1) and compared data with those obtained after 1 mo (group 2). In both groups 1 and 2, plasma ANP levels significantly correlated with PCWP. The slope of the linear regression line between the PCWP and ANP in group 1 was significantly lower, by about one-third, than that in group 2. In addition, we examined changes in ANP levels and left ventricular end-diastolic pressure (LVEDP) over 180 min after AMI induced by injection of microspheres into the left coronary arteries of three dogs. The LVEDP and ANP levels 30 min after AMI were significantly higher than those before; however, despite the persistent high LVEDP during the 180 min after AMI, ANP levels decreased gradually and significantly to 63% of the peak level at 150 min. These findings suggest that the secretion of ANP during the acute phase of myocardial infarction may be insufficient relative to the chronic phase.     

Biphasic and monophasic pattern of brain natriuretic peptide release in acute myocardial infarction

This study evaluated brain natriuretic peptide (BNP) release in acute myocardial infarction (AMI), absolute values as well as pattern of its release. There are two different patterns of BNP release in AMI; monophasic pattern--concentration in the first measurement is higher than in the second one, and biphasic pattern--concentration in the first measurement is lower than in the second one. We observed significance of biphasic and monophasic pattern of BNP release related to diagnostic and prognostic value. We included in this prospective observational study total of 75 AMI patients, 52 males and 23 females, average age of 62.3 +/- 10.9 years with range of 42 to 79 years. BNP was measured and pattern of its release was evaluated. In AMI group BNP levels were significantly higher than in controls (462.88 pg/mL vs. 35.36 pg/mL, p < 0.001). We found statistically significant real negative correlation (p < 0.05) between BNP concentration and left ventricle ejection fraction (LVEF) with high correlation coefficient (r = -0.684). BNP concentrations were significantly higher among patients in Killip class II and III compared to Killip class I; Killip class I BNP = 226.18 pg/mL vs. Killip class II 622.51 pg/mL vs. Killip class III 1530.28 pg/mL, p < 0.001. BNP concentrations were significantly higher in patients with; (i) myocardial infarction vs. controls; (BNP 835.80 pg/mL vs. 243.03 pg/mL); (ii) in pts with positive major adverse cardiac events (MACE) vs. negative MACE (BNP 779.08 pg/mL vs. 242.28 pg/mL, p < 0.001); (iii) in pts with positive compared to negative left ventricle (LV) remodelling (BNP 840.77 pg/mL vs. 341.41 pg/mL, p < 0.001). Group with biphasic pattern of BNP release had significantly higher BNP concentration compared to monophasic pattern group. In biphasic pattern group we found significant presence of lower LVEF, Killip class II and III, LV remodelling and MACE. We found that BNP is strong marker of adverse cardiac events in patients presenting with a myocardial infarction. In our AMI group we found significant elevation of BNP and it is suspected that second peak secretion is not only due to systolic dysfunction and subsequent remodeling of LV but also due to impact of ischaemia. Patients with biphasic pattern probably have worse prognosis due to severe coronary heart disease. Besides its diagnostic role as a simple blood marker of systolic function, BNP is also important prognostic marker who helps making clinical decision about early invasive vs. conservative management.     

Atrial natriuretic peptide, B-type natriuretic peptide, and serum collagen markers after acute myocardial infarction.

Experimental data suggest that atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) act locally as antifibrotic factors in heart. We investigated the interrelationships of natriuretic peptides and collagen markers in 93 patients receiving thrombolytic treatment for their first acute myocardial infarction (AMI). Collagen formation following AMI, evaluated as serum levels of amino terminal propeptide of type III procollagen, correlated with NH(2)-terminal proANP (r = 0.45, P < 0.001), BNP (r = 0.55, P < 0.001) and NH(2)-terminal proBNP (r = 0.50, P < 0.01) on day 4 after thrombolysis. Levels of intact amino terminal propeptide of type I procollagen decreased by 34% (P < 0.001), and levels of carboxy terminal cross-linked telopeptide of type I collagen (ICTP) increased by 65% (P < 0.001). ICTP levels correlated with NH(2)-terminal proBNP (r = 0.25, P < 0.05) and BNP (r = 0.28, P < 0.05) on day 4. Our results suggest that ANP and BNP may act as regulators of collagen scar formation and left ventricular remodeling after AMI in humans. Furthermore, degradation of type I collagen is increased after AMI and may be regulated by BNP.     

Biosynthesis, secretion, and receptor selectivity of human brain natriuretic peptide.

Biosynthesis, secretion and receptor selectivity of human brain natriuretic peptide (hBNP) were studied. The BNP mRNA level in the ventricle was approximately 40% of that in the atrium and, taking tissue weight into account, the total amount of BNP mRNA in the ventricle was about twofold greater than the total amount in the atrium. The plasma BNP-like immuno-reactivity (-LI) level in normal subjects was 0.90 +/- 0.07 fmol/mL, which was 16% of the ANP-LI level. In contrast, the plasma BNP-LI level markedly increased in patients with congestive heart failure, with a progressive rise in proportion to its severity. There was a significant step-up of the plasma BNP-LI level in the coronary sinus (CS) compared with that in the aortic root, and the difference in the plasma BNP-LI level between the CS and the aorta (Ao), delta (CS-Ao)BNP, increased with the severity of congestive heart failure. In addition, the difference in the BNP-LI level between the anterior inverventricular vein (AIV) draining the ventricle and the aorta (delta (AIV-Ao)BNP) was comparable to delta (CS-Ao) BNP, indicating that BNP is secreted predominantly from the ventricle. Binding ability to human clearance receptors (C receptors) and cyclic GMP (cGMP) production of hBNP were investigated and compared with those of ANP. hBNP bound to human C receptors very weakly (about 7%), but exerted cGMP production similar to ANP in cultured human mesangial cells and bovine endothelial cells. In conclusion, hBNP is a novel cardiac hormone mainly synthesized in and secreted from the ventricle and plays physiological and pathophysiological roles in the dual cardiac natriuretic peptide system.     

Increased secretion of brain natriuretic peptide and atrial natriuretic peptide, but not sufficient to induce natriuresis in rats with nephrotic syndrome.

The levels of immunoreactive brain natriuretic peptide (ir-BNP) and immunoreactive atrial natriuretic peptide (ir-ANP) were evaluated by radioimmunoassay in both the atrium, ventricle and plasma of adriamycin-induced nephrotic rats and control rats. There was no difference in right and left atrial concentrations of ir-BNP, however, a higher right atrial concentration of ir-ANP was observed in nephrotic rats than in controls (p less than 0.01). The ventricular ir-BNP and ir-ANP were increased in nephrotic rats compared to controls (BNP: p less than 0.001, ANP: p less than 0.001). Cardiac BNPs were composed of pro-BNP (gamma-BNP) and its C-terminal 45-amino-acid peptide (BNP-45). The ratio of BNP-45/gamma-BNP in nephrotic rats was higher than that of controls in both atria and in the ventricle. Plasma ir-BNP and ir-ANP were significantly higher in nephrotic rats than in controls (BNP: p less than 0.001, ANP: p less than 0.001), and each level was negatively correlated with urinary sodium excretion in nephrotic rats (BNP: r = -0.84, p less than 0.001, ANP: r = -0.88, p less than 0.001). These results suggest that production and secretion of both BNP and ANP are concomitantly stimulated by a decreased renal ability to eliminate sodium and water, but this secretion is insufficient to induce effective natriuresis in nephrotic rats.     

Atrial and brain natriuretic peptide in adrenal steroidogenesis.

We elucidated the role of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in human and bovine adrenocortical steroidogenesis. The urinary volume, sodium excretion and cyclic GMP (cGMP) excretion and plasma cGMP were markedly increased by the synthetic alpha-human ANP (alpha-hANP) infusion in healthy volunteers. Plasma arginine vasopressin (AVP) and aldosterone levels were significantly suppressed. Both ANP and BNP inhibited aldosterone, 19-OH-androstenedione, cortisol and DHEA secretion dose-dependently and increased the accumulation of intracellular cGMP in cultured human and bovine adrenal cells. alpha-hANP significantly suppressed P450scc-mRNA in cultured bovine adrenal cells stimulated by ACTH. Autoradiography and affinity labeling of [125I]hANP, and Scatchard plot demonstrated a specific ANP receptor in bovine and human adrenal glands. Purified ANP receptor from bovine adrenal glands identified two distinct types of ANP receptors, one is biologically active, the other is silent. A specific BNP receptor was also identified on the human and bovine adrenocortical cell membranes. The binding sites were displaced by unlabelled ANP as well as BNP. BNP showed an effect possibly via a receptor which may be shared with ANP. The mean basal plasma alpha-hANP level was 25 +/- 5 pg/ml in young men. We confirmed the presence of ANP and BNP in bovine and porcine adrenal medulla. Plasma or medullary ANP or BNP may directly modulate the adrenocortical steroidogenesis. We demonstrated that the lack of inhibitory effect of alpha-hANP on cultured aldosterone-producing adenoma (APA) cells was due to the decrease of ANP-specific receptor, which caused the loss of suppression of aldosterone and an increase in intracellular cGMP.     

Atrial natriuretic peptide levels during development of chronic heart failure after myocardial infarction in rats

Serum levels of atrial natriuretic peptide (ANP) are elevated in chronic heart failure presumably due to dilatation of the left atrium resulting from increases in intracardiac pressures. To define the time course of changes in serum ANP levels and to determine the relationship to left ventricular end-diastolic pressure, rats were subjected to coronary artery ligation to produce myocardial infarction and left ventricular failure. Atrial natriuretic peptide levels were measured weekly for four weeks thereafter. In rats with myocardial infarction and elevation of left ventricular end-diastolic pressure there was no change in ANP levels at 7 and 14 days. However, at day 21 and 28, ANP levels were elevated more than 3 fold. There was a correlation between ANP levels and left ventricular end-diastolic pressures. There was no correlation between ANP levels and right atrial pressures or serum sodium concentrations. We conclude that the chronic elevation of left ventricular end-diastolic pressure is required to produce an increase in ANP after myocardial infarction which results in chronic heart failure.     

Protective effect of peptide semax the rat heart in acute myocardial infarction

Semax, a member of ACTH-derived peptides family, has been employed in the treatment of acute ischemic stroke in patients. It decreased neurological deficit and reduced NO hyperproduction in the rat brain, caused by acute cerebral hypoperfusion. We suggested that semax is also able to protect rat heart from ischemic damage in acute myocardial infaction (AMI). AMI was induced by left coronary artery occlusion, myocardial ischemic area averaged 30 % of left ventricle. In 2 hours after coronary occlusion, the AMI group developed 11 % reduced mean arterial blood pressure and 48 % increased diastolic blood pressure in left ventricle in comparison with sham-operated control group. However, infusion of either dobutamine, which directly stimulates myocardial contractility, or sodium nitroprusside and phenylephrine, that change vascular resistance and thus cardiac afterload, did not reveal distinctions in hemodynamic parameters between groups. These data indicate absense or only moderate cardiac dysfunction in rats with AMI and are consistent wih morphometrical and histochemical studies that did not detect any necrotic or apoptotic (TUNEL-test) changes in left ventricular cardiomyocytes in spite of development of distinct ischemic disturbances of mitochondria and nuclear in about 50 % of cardiomyocytes in 2 hours after AMI. Semax (150 microg/kg), given i. p. 15 min and 2 hours after coronary occlusion, caused no effect on cardiac function, but completely prevented ischemia-induced ultrastructural changes of cardiomyocytes. This protective effect was accompanied by the ability of peptide to blunt the increase in plasma concentrations of nitrates, observed in AMI group.     

Hemodynamic monitoring in acute myocardial infarction.

The main cause of in-hospital death in patients with acute myocardial infarction is the "power failure syndrome". Hemodynamic monitoring provides precise and current data on the filling and output status of the left ventricle and, when indicated, the right ventricle. The information obtained is used to determine the hemodynamic status more precisely than is possible from conventional clinical assessment. It permits categorization of patients by hemodynamic status; the hemodynamic subset classification of Forrester, Diamond and Swan is a powerful tool in guiding therapy and establishing prognosis in individual patients. In addition to guiding the initiation of therapy, hemodynamic monitoring is useful in the continuing assessment of potent and complex treatment. This therapy is directed at resolving hemodynamic derangements without unfavourably altering the myocardial oxygen supply-demand relationship. Specific clinical indications for hemodynamic monitoring may include confusing or complicated clinical situations in which diagnostic problems exist, complicating mechanical derangements, severe congestive heart failure, cardiogenic shock and clinical research in acute myocardial infarction.