Secretion of atrial natriuretic peptide from the heart in man

Plasma concentrations of atrial natriuretic peptide were measured in eight patients undergoing elective cardiac catheterisation and angiography. All patients had normal resting pressures in the cardiac chambers and no clinical evidence of heart failure. Plasma atrial natriuretic peptide rose significantly from the superior vena cava into the right atrium and right ventricle. The increase into the right atrium was variable, with no increase in three subjects, but there was a consistent increase in all subjects from the superior vena cava to to the right ventricle. These findings in the right atrium are probably caused by inadequate mixing and streaming of blood from the coronary sinus containing high concentrations of atrial natriuretic peptide. There was no increase in the concentration of natriuretic peptide from the pulmonary artery to the left ventricle, but the concentrations in the left ventricle were significantly higher than in the superior vena cava. These findings demonstrate that the heart secretes atrial natriuretic peptides in the absence of cardiac failure. Studies based on sampling of the right atrium will not accurately measure cardiac secretion of atrial natriuretic peptide and will therefore be likely to obscure the mechanisms responsible for regulating its secretion. The right ventricle and pulmonary artery are the best sampling sites to measure atrial natriuretic peptide release from the right atrium.     

Secretion of atrial natriuretic peptide from the heart in man.

Plasma concentrations of atrial natriuretic peptide were measured in eight patients undergoing elective cardiac catheterisation and angiography. All patients had normal resting pressures in the cardiac chambers and no clinical evidence of heart failure. Plasma atrial natriuretic peptide rose significantly from the superior vena cava into the right atrium and right ventricle. The increase into the right atrium was variable, with no increase in three subjects, but there was a consistent increase in all subjects from the superior vena cava to to the right ventricle. These findings in the right atrium are probably caused by inadequate mixing and streaming of blood from the coronary sinus containing high concentrations of atrial natriuretic peptide. There was no increase in the concentration of natriuretic peptide from the pulmonary artery to the left ventricle, but the concentrations in the left ventricle were significantly higher than in the superior vena cava. These findings demonstrate that the heart secretes atrial natriuretic peptides in the absence of cardiac failure. Studies based on sampling of the right atrium will not accurately measure cardiac secretion of atrial natriuretic peptide and will therefore be likely to obscure the mechanisms responsible for regulating its secretion. The right ventricle and pulmonary artery are the best sampling sites to measure atrial natriuretic peptide release from the right atrium.     

Atrial natriuretic peptide in chronic heart failure in the rat: a correlation with ventricular dysfunction

To assess the relation between atrial natriuretic peptide and ventricular dysfunction, we simultaneously measured both atrial and plasma immunoreactive atrial natriuretic peptide concentrations in rats 4 weeks after myocardial infarction induced by left coronary artery ligation. When compared to controls (n = 39), rats with infarction (n = 16) had markedly elevated plasma immunoreactive atrial natriuretic peptide concentrations (1205.8 +/- 180.9 vs. 126.7 +/- 8.9 pg/ml, p less than 0.001) and reduced immunoreactive atrial natriuretic peptide concentrations in right and left atria (31.4 +/- 4.6 vs. 61.2 +/- 3.2 ng/mg, p less than 0.001; 14.9 +/- 2.2 vs. 32.7 +/- 2.4 ng/mg, p less than 0.001, respectively). Right ventricular weight increased in proportion to infarct size, and both were correlated with plasma immunoreactive atrial natriuretic peptide levels (r = 0.825, p less than 0.001 and r = 0.816, p less than 0.001, respectively). Right atrial immunoreactive atrial natriuretic peptide content was significantly higher than left in both controls and rats with infarction. Both right and left atrial immunoreactive atrial natriuretic peptide concentrations were negatively correlated with both right ventricular weight as well as plasma immunoreactive atrial natriuretic peptide concentrations (right atrium: r = -0.816, p less than 0.001, r = -0.708, p less than 0.01; left atrium: r = -0.687, p less than 0.01, r = -0.644, p less than 0.01, respectively). These results suggest that chronic stimulation of atrial natriuretic peptide release from both atria is associated with increased turnover and depleted stores of atrial natriuretic peptide in atria in proportion to the severity of heart failure. It also suggests that plasma atrial natriuretic peptide levels may be used as a reliable index of cardiac decompensation in chronic heart failure.     

Right coronary artery stenosis is associated with impaired cardiac endocrine function during exercise

AIMS: Resting plasma levels of atrial natriuretic peptide and B-typenatriuretic peptide rise with left ventricular dysfunction,but little is known about effects of cardiac ischaemia on atrialnatriuretic peptide and B-type natriuretic peptide levels duringexercise. We investigated exercise levels of atrial natriureticpeptide and B-type natriuretic peptide in patients with suspectedangina to determine whether these measurements could improvenon-invasive assessment of coronary disease severity. METHODS AND RESULTS: One hundred patients performed an exercise test (Bruce protocol)within 2 weeks of coronary angiography. Plasma levels of atrialnatriuretic peptide and B-type natriuretic peptide were measuredat rest and at peak exercise. Multivariate regression analysiswas used to assess effects of age, sex, coronary anatomy, exercisetime and ventricular function on atrial natriuretic peptideand B-type natriuretic peptide levels. Increasing age and femalesex were significantly associated with higher resting atrialnatriuretic peptide levels; age alone was associated with higherexercise atrial natriuretic peptide levels. As expected, leftventricular end-diastolic pressure and disease of left anteriordescending and circumflex coronary arteries were associatedwith increased resting B-type natriuretic peptide levels. However,the usual rise in B-type natriuretic peptide levels during exercisewas independently reduced by disease of the right coronary artery. CONCLUSION: This paradoxical effect of right coronary artery disease limitsthe value of natriuretic peptide measurements as predictorsof coronary disease severity. Impaired release of B-type natriureticpeptide may reduce exercise tolerance in patients with rightcoronary artery disease.     

Levels of brain natriuretic peptide in children with right ventricular overload due to congenital cardiac disease

OBJECTIVE: To evaluate the role of the concentration of brain natriuretic peptide in the plasma, and its correlation with haemodynamic right ventricular parameters, in children with overload of the right ventricle due to congenital cardiac disease. METHODS: We studied 31 children, with a mean age of 4.8 years, with volume or pressure overload of the right ventricle caused by congenital cardiac disease. Of the patients, 19 had undergone surgical biventricular correction of tetralogy of Fallot, 11 with pulmonary stenosis and 8 with pulmonary atresia, and 12 patients were studied prior to operations, 7 with atrial septal defects and 5 with anomalous pulmonary venous connections. We measured brain natriuretic peptide using Triage(R), from Biosite, United States of America. We determined end-diastolic pressures of the right ventricle, and the peak ratio of right to left ventricular pressures, by cardiac catheterization and correlated them with concentrations of brain natriuretic peptide in the plasma. RESULTS: The mean concentrations of brain natriuretic peptide were 87.7, with a range from 5 to 316, picograms per millilitre. Mean end-diastolic pressure in the right ventricle was 5.6, with a range from 2 to 10, millimetres of mercury, and the mean ratio of right to left ventricular pressure was 0.56, with a range from 0.24 to 1.03. There was a positive correlation between the concentrations of brain natriuretic peptide and the ratio of right to left ventricular pressure (r equal to 0.7844, p less than 0.0001) in all patients. These positive correlations remained when the children with tetralogy of Fallot, and those with atrial septal defects or anomalous pulmonary venous connection, were analysed as separate groups. We also found a weak correlation was shown between end-diastolic right ventricular pressure and concentrations of brain natriuretic peptide in the plasma (r equal to 0.5947, p equal to 0.0004). CONCLUSION: There is a significant correlation between right ventricular haemodynamic parameters and concentrations of brain natriuretic peptide in the plasma of children with right ventricular overload due to different types of congenital cardiac disease. The monitoring of brain natriuretic peptide may provide a non-invasive and safe quantitative follow up of the right ventricular pressure and volume overload in these patients.     

Atrial natriuretic peptide release responds to atrial stretch and not to atrial pressure: observations during pericardiocentesis in a young woman

The effect of pericardiocentesis on the plasma concentration of atrial natriuretic peptide was studied in a patient with cardiac tamponade. Plasma atrial natriuretic peptide concentrations rose sharply from 42 pmol l-1 to a maximum of 150 pmol l-1 with a corresponding fall in mean right atrial pressure from 20 mmHg to 6 mmHg. Our results suggest that atrial 'stretch' (or transmural pressure) rather than atrial pressure per se, is the primary stimulus for atrial natriuretic peptide release in man.     

Effect of induced ventricular tachycardia on atrial natriuretic peptide in humans

The effects of induced sustained ventricular tachycardia on the release of plasma-immunoreactive atrial natriuretic peptide were evaluated in 11 adult patients undergoing diagnostic electrophysiologic study. Plasma concentrations of atrial natriuretic peptide withdrawn from the right atrium before and during sustained ventricular tachycardia (mean tachycardia cycle length 320 +/- 68 ms, duration greater than 30 s) were determined by radioimmunoassay. Hemodynamic measurements included phasic femoral artery blood pressure and mean right atrial blood pressure before and during ventricular tachycardia. During ventricular tachycardia, atrial natriuretic peptide increased from 93 +/- 49 pg/ml to 234 +/- 195 pg/ml (p less than 0.05), systolic arterial blood pressure decreased from 120 +/- 16 to 70 +/- 23 mm Hg (p less than 0.001), diastolic arterial blood pressure decreased from 63 +/- 8 to 51 +/- 16 mm Hg (p = NS) and mean right atrial blood pressure increased from 3 +/- 1 to 8 +/- 5 mm Hg (p less than 0.02). In six patients, all hemodynamic variables and the atrial natriuretic peptide were measured during repeated stimulation protocols to investigate the effect of ventricular stimulation for ventricular tachycardia induction on atrial natriuretic factor release. Compared with the values obtained during sinus rhythm, there was no significant increase in atrial natriuretic factor during ventricular stimulation at a cycle length of 600 ms (45 +/- 20 versus 52 +/- 21 pg/ml) or at a cycle length of 400 ms (45 +/- 20 versus 57 +/- 18 pg/ml). No significant linear relation could be found among the changes in mean right atrial pressure, systolic arterial blood pressure and the increase in atrial natriuretic peptide.(ABSTRACT TRUNCATED AT 250 WORDS)     

Deconvolution analysis of cardiac natriuretic peptides during acute volume overload

Cardiac natriuretic peptides, especially amino terminal pro-Brain Natriuretic Peptide (NT-proBNP), are emerging as powerful circulating markers of cardiac function. However, the in vivo secretion and elimination (t1/2) of these peptides during acute volume overload have not been studied. We present the first report of the secretion and elimination of cardiac natriuretic peptides, based on deconvolution analysis of endogenous ovine plasma levels measured by specific radioimmunoassay. Four normal, conscious sheep underwent rapid right ventricular pacing (225 bpm) for 1 hour to stimulate acute cardiac natriuretic peptide release. Plasma samples and right atrial pressure measurements were taken at regular intervals 30 minutes before, during, and 4 hours after pacing. Baseline right atrial pressure significantly increased (P:=0.02) during the 1 hour of pacing in association with a prompt increase in plasma BNP (P:=0.03), atrial natriuretic peptide (P:=0.01), and NT-proBNP (P:=0.02). Deconvolution analysis showed that the t1/2 of NT-proBNP (69.6+/-10.8 minutes) was 15-fold longer than BNP (4.8+/-1. 0 minutes). Despite sustained increases in atrial pressure, cardiac secretion of natriuretic peptides (particularly atrial natriuretic peptide) fell during the pacing period, suggesting a finite source of peptide for secretion. Size-exclusion high-performance liquid chromatography revealed NT-proBNP to be a single immunoreactive peak, whereas BNP comprised at least 2 immunoreactive forms. These findings, especially the prompt secretion of BNP and the prolonged t1/2 of NT-proBNP, clarify the metabolism of BNP forms and help to explain the diagnostic value of NT-proBNP measurement as a sensitive marker of ventricular function.     

Atrial strain is the main determinant of release of atrial natriuretic peptide

We studied the response of atrial natriuretic peptide to the hemodynamic and renin-aldosterone variations occurring in four patients who developed cardiac tamponade, either occurring in idiopathic fashion in one or secondary to metastatic involvement of the pericardium in three. Right atrial pressure, heart rate and arterial blood pressure were monitored and serial blood samples were taken before and over three hours after pericardiocentesis. During cardiac tamponade, normal levels of atrial natriuretic peptide (mean +/- SEM: 54 +/- 7.4 pg/ml) were observed in the plasma despite increased right atrial pressure (23 +/- 3.8 cm H2O) and heart rates (98 +/- 4.4). Removal of pericardial fluid (540 to 1160 ml) was associated at first with a 200% increase in plasma concentrations of atrial natriuretic peptide (108 +/- 8.8 pg/ml; P less than 0.001), then with a gradual decline toward normal levels, simultaneous with the normalization of right atrial pressure and heart rate. Activity of renin and concentrations of aldosterone in the plasma were increased during tamponade and returned gradually to normal after pericardiocentesis (3.8 +/- 0.9 to 1.2 +/- 0.3 ng/ml/h and 20 +/- 4.2 to 9 +/- 3.2 ng/dl, respectively; P less than 0.01). These data confirm that atrial strain, not intracavitary pressure in itself nor heart rate, is the main determinant of the acute release of atrial natriuretic peptide, which is associated with a suppressing effect on the renin-aldosterone system. In addition, our data indicate that secretion of atrial natriuretic peptide during cardiac tamponade is not stimulated by secondary hyperaldosteronism.     

Atrial natriuretic peptide in portal vein-ligated rats: alterations in cardiac production, plasma level and glomerular receptor density and affinity.

The atrial natriuretic peptide hormonal system is altered to a variable degree in patients with cirrhosis. Portal pressure and portal-systemic shunting are also varied in cirrhosis. We used a portal vein-ligated rat model with predictable portal hypertension to study the effects of portal hypertension alone on the atrial natriuretic peptide hormonal system. Sham-operated rats were used as controls. Mean portal pressure was significantly increased in portal vein-ligated rats (portal vein-ligated rats, 21.7 +/- 0.74 cm H2O; sham-operated rats, 13.7 +/- 0.47 cm H2O; p less than 0.0001). Plasma atrial natriuretic peptide decreased 50% in the portal vein-ligated rats (p less than 0.0001). Atrial natriuretic peptide messenger RNA level was decreased by 40% to 60% in the left and right atria and in the ventricles of portal vein-ligated rats (p less than 0.05 for each chamber). Only one class of glomerular binding site was identified by competitive binding studies. The atrial natriuretic peptide glomerular receptor density increased in the portal vein-ligated rats (portal vein-ligated rats, 1,660 +/- 393; sham-operated 725 +/- 147 fmol/mg protein, p less than 0.02), whereas affinity decreased (portal vein-ligated, 1.69 +/- 0.49; sham-operated, 0.55 +/- 0.12 nmol/L, p less than 0.02). No difference was seen in the amount of cyclic GMP generated by atrial natriuretic peptide stimulation in isolated glomeruli from portal vein-ligated and sham-operated rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Localization of brain and atrial natriuretic peptide in human and porcine heart.

We have compared the localization of brain and atrial natriuretic peptide-like immunoreactivity in human and porcine hearts, using immunohistochemical techniques at both the light and ultrastructural level and specific antisera to amino-(cardiodilatin) and carboxy-terminal regions of the atrial natriuretic precursor molecule and to brain natriuretic peptide. Atrial myocardial cells in human fetal, normal adult and failing explanted hearts, displayed immunoreactivity for both brain and atrial natriuretic peptide-like sequences. At the subcellular level, brain natriuretic peptide-, cardiodilatin- and alpha-atrial natriuretic peptide-like immunoreactivity were co-localized to secretory granules in atrial myocardial cells. Immunoreactivity was also detected in the left (64%) and right ventricular free walls (23%) of 22 failing explanted hearts, but not in donor cardiac tissues. A gradient of natriuretic peptide immunostaining was observed across ventricular free walls and immunoreactivity for both natriuretic peptide sequences co-localized to secretory granules in a subpopulation of myocardial cells, concentrated in subendocardial regions of the ventricular walls. Brain and atrial natriuretic peptide-like immunoreactivity were also demonstrated in porcine atrial myocardium and cells of the ventricular conduction system. The parallel distribution of cardiac brain and atrial natriuretic peptide-like immunoreactivity suggests a dual regulation and co-storage of the natriuretic peptides in human and porcine hearts.     

Atrial natriuretic peptide in severe heart failure: response to controlled changes in atrial pressures during intravenous nitroglycerin therapy.

Atrial natriuretic peptide (ANP) levels were measured in 17 patients with severe congestive heart failure (New York Heart Association functional class IV), and the response of the peptide was studied during changes in cardiac filling pressures induced by a 24-hour infusion of nitroglycerin. In the control state plasma ANP levels (687 +/- 551 pg/ml) were 10-fold normal. During the administration of nitroglycerin, natriuretic peptide levels decreased (p less than 0.005) with changes matching very closely the decreases in pulmonary arterial wedge and right atrial pressures, a 1% mean decrease in the peptide level for every 1.5 to 2% mean change in atrial filling pressures. In patients with hemodynamic tolerance to constant-dose nitroglycerin infusion, the resulting increase in atrial pressures was accompanied by an appropriate secondary increase in the plasma ANP level. During the 24-hour study period there was a direct linear relationship between both wedge (r = 0.93, p = 0.007) and right atrial (r = 0.93, p = 0.008) pressures and the plasma ANP level, with a zero-pressure ANP intercept near normal (69 pg/ml for wedge, 174 pg/ml for right atrial pressure). The findings were no different in a subgroup of five patients receiving simultaneous treatment with captopril, except that plasma renin activity was higher and the aldosterone level lower than in the control group by a factor of approximately 2.5. The close relationship and tracking of atrial pressure and natriuretic peptide curves suggested that the sensitivity of the atrial stretch response to changes in atrial filling pressures was maintained in severe congestive heart failure.     

Isolated atrial amyloid contains atrial natriuretic peptide: a report of six cases

Twenty five specimens of the human right atrial appendage were examined for immunoreactivity to alpha human atrial natriuretic peptide. In the electron microscope characteristic amyloid fibrils were identified around small blood vessels and adjacent to atrial muscle cells in eight of the surgical cases and in two necropsy cases. In six cases, four surgical and two necropsy, these fibrils contained immunoreactive alpha human atrial natriuretic peptide. Amyloid is known to occur in peptide secreting endocrine tumours and immunoreactive peptide may be incorporated in the amyloid matrix. The demonstration of atrial amyloid containing immunoreactive alpha human atrial natriuretic peptide suggests that some deposits of cardiac amyloid are of a type analogous to that found in other endocrine organs.     

Isolated atrial amyloid contains atrial natriuretic peptide: a report of six cases.

Twenty five specimens of the human right atrial appendage were examined for immunoreactivity to alpha human atrial natriuretic peptide. In the electron microscope characteristic amyloid fibrils were identified around small blood vessels and adjacent to atrial muscle cells in eight of the surgical cases and in two necropsy cases. In six cases, four surgical and two necropsy, these fibrils contained immunoreactive alpha human atrial natriuretic peptide. Amyloid is known to occur in peptide secreting endocrine tumours and immunoreactive peptide may be incorporated in the amyloid matrix. The demonstration of atrial amyloid containing immunoreactive alpha human atrial natriuretic peptide suggests that some deposits of cardiac amyloid are of a type analogous to that found in other endocrine organs.     

Brain natriuretic peptide concentration in pericardial fluid is independently associated with atrial fibrillation after off-pump coronary artery bypass surgery

OBJECTIVES: Postoperative atrial fibrillation is associated with the increased incidence of morbidities and mortality. Predisposing determinants of atrial fibrillation development after off-pump coronary artery bypass grafting remain unclear. We hypothesized that pericardial fluid natriuretic peptide concentrations have a predictive value for developing postoperative atrial fibrillation in patients who have undergone off-pump coronary artery bypass grafting. METHODS: We prospectively measured atrial natriuretic peptide and brain natriuretic peptide concentrations in plasma and pericardial fluid in 42 consecutive patients undergoing off-pump coronary artery bypass grafting, then continuously observed the occurrence of atrial fibrillation following off-pump coronary artery bypass grafting until the time of discharge. RESULTS: Postoperative atrial fibrillation was documented in nine patients (21%, atrial fibrillation group), and not in 33 patients (no atrial fibrillation group). Between the groups, there was neither significant difference in plasma atrial natriuretic peptide concentrations nor in pericardial atrial natriuretic peptide concentrations. Plasma brain natriuretic peptide concentrations were comparable in both groups [56.2 (interquartile range 42.7-102.8) vs. 35.2 pg/ml (13.8-75.0), P=0.07]. Pericardial fluid brain natriuretic peptide concentrations were significantly higher in the atrial fibrillation group than in the no atrial fibrillation group [188.0 (124.8-411.0) vs. 39.3 pg/ml (10.0-88.4), P=0.0001]. In a multivariable logistic regression model, pericardial brain natriuretic peptide concentration was significantly associated with a higher risk of postoperative atrial fibrillation (odds ratio=3.0 every 50 pg/ml increase; 95% confidence interval, 1.1-8.6; P=0.04). CONCLUSION: Our results suggested that pericardial fluid brain natriuretic peptide concentration is independently associated with the development of atrial fibrillation after off-pump coronary artery bypass grafting.     

Atrial natriuretic peptide during pacing in controls and patients with coronary arterial disease

At rest, during cardiac catheterization, aortic plasma levels of immunoreactive atrial natriuretic peptide did not differ between 10 controls with atypical chest pains and normal coronary arteries and 9 patients with stable angina pectoris and coronary arterial disease (55.2 +/- 19.8 vs. 64.8 +/- 19.8 pg/ml, NS). Nor did atrial natriuretic peptide values differ between the two groups during or after atrial pacing (150 beats/minute), which induced electrocardiographic and metabolic signs of acute myocardial ischaemia in the patients with coronary arterial disease but in none of the controls. Pacing, when carried out for more than 300 seconds, induced an increase of plasma atrial natriuretic peptide that correlated with duration of pacing (r = 0.80, P less than 0.001), and similarly in controls and patients with coronary arterial disease. In a second part of the study, which included 2 controls and 2 patients with coronary arterial disease, post-pacing coronary sinus concentrations of atrial natriuretic peptide were 10-20 times higher than peripheral levels (415- greater than 890 pg/ml). The concentration of atrial natriuretic peptide rose as blood from the caval veins (34 +/- 7 pg/ml) entered the right atrium (56 +/- 24 pg/ml), but thereafter was unchanged in the pulmonary artery (51 +/- 3 pg/ml) and the aorta (46 +/- 9 pg/ml). In conclusion, the results gave no evidence for ischaemic heart disease without congestive cardiac failure to be associated with altered levels of atrial natriuretic peptide. It was confirmed that atrial pacing stimulates the secretion of atrial natriuretic peptide which is produced by the heart and released via the coronary sinus into the circulation.     

Effect of congestive heart failure on rate of atrial natriuretic factor release in response to stretch and isoprenaline

STUDY OBJECTIVE--The aim was to investigate the pattern of release of atrial natriuretic factor induced by mechanical and adrenergic stimulation from atria of rats with or without congestive heart failure. DESIGN--Monocrotaline, a pyrrolizidine alkaloid, was given to rats to cause severe pulmonary hypertension, leading to a marked degree of right ventricular hypertrophy and failure. Measurements of noradrenaline and atrial natriuretic factor were performed in each cardiac chamber and in plasma. Right and left atria of control rats and rats with congestive heart failure were isolated and subjected to mechanical or adrenergic stimulation to study the in vitro release of atrial natriuretic factor. MATERIALS--Studies were performed on plasma, ventricles, and isolated right and left atria of 276 male Wistar rats, 80-100 g weight, with or without congestive heart failure. MEASUREMENTS AND MAIN RESULTS--In monocrotaline rats right and left ventricular concentrations of noradrenaline were significantly reduced. In the same rats concentrations of atrial natriuretic factor fell to 15.2% in the right atria and to 65.5% in the left atria. Whole heart content of atrial natriuretic factor was diminished, while plasma concentrations were increased sevenfold. Isolated hypertrophied right atria of failing hearts did not release atrial natriuretic factor in response to stretch or to isoprenaline (10(-9)M) and they were insensitive to the inotropic action of isoprenaline. On the other hand, non-hypertrophied left atria from the same animals released increased amounts of atrial natriuretic factor under basal conditions and after both stimuli, despite reduced tissue stores of the peptide. CONCLUSIONS--Heart failure may deplete cardiac stores of noradrenaline and atrial natriuretic factor, especially in hypertrophied chambers, and can result in a decrease in the release of atrial natriuretic factor from atrial tissue in response to mechanical and adrenergic stimulation.     

Elevation of atrial natriuretic peptide prohormone. Hemodynamic background of the elevation of N-terminal natriuretic peptide prohormone in children with congenital heart disease.

We postulated previously that variables related to pulmonary flow are independent predictors of levels of atrial natriuretic peptide in children with congenital heart disease. The aim of this study was to test this hypothesis in relation to other hemodynamic and clinical variables. During catheterization we measured the levels of plasma N-terminal atrial natriuretic peptide prohormone in the plasma of 68 children with congenital heart disease. All had undergone complete clinical, echocardiographic and invasive hemodynamic investigations. The influence on the prohormone was analyzed for 10 different variables in a multiple linear regression model. The variability could be explained in large parts (adjusted R2 =77.2%) by variations in atrial pressures or sizes, together with the degree of excessive pulmonary blood flow and signs of heart failure. A value for atrial natriuretic peptide prohormone above 800 pmol/l predicted hemodynamic imbalance (defined as elevated pressures in left or right atrium or the pulmonary arteries, and/or Qp/Qs > 1.5) with a specificity of 94%, a sensitivity of 73%, a positive likelihood ratio of 12.2, and a negative likelihood ratio of 0.29. In conclusion, variables related to pulmonary blood flow are influential determinants of the levels of atrial natriureic peptide in children with congenital heart disease. Atrial pressures, and symptoms of heart failure are also of major importance.     

The role of frequency of atrial contraction versus atrial pressure in atrial natriuretic peptide release

This study was designed to investigate the role of frequency of atrial contraction compared to acute increases in right atrial pressure in the regulation of atrial natriuretic peptide (ANP) release in humans. The studies were performed in patients undergoing electrophysiological study. In group 1 (n = 12) the rate of atrial contraction was increased by continuous rapid right atrial pacing at a rate of 120 beats/min (bpm; group 1A; n = 6) or 176 bpm (group lb; n = 6) for 5 min. No increases in atrial pressure or circulating ANP occurred in response to atrial tachycardia. In contrast, continuous rapid right ventricular pacing (group II: n = 12) at ventricular rates of 120 bpm (group IIa; n = 6) and 150 bpm (group IIb; n = 6) increased both right atrial pressure and circulating ANP. These results demonstrate that, in contrast to studies in vitro, increases in the frequency of atrial contraction in the absence of increases in atrial pressure do not release atrial natriuretic peptide. These studies, therefore, support the conclusion that atrial pressure is the primary physiological stimulus for ANP.