Plasma Concentrations of Atrial and Brain Natriuretic Peptides and Cyclic Guanosine Monophosphate in Response to Dobutamine Infusion in Patients with Surgically Repaired Tetralogy of Fallot

We examined the plasma concentrations of atrial and brain natriuretic peptides (ANP and BNP) and cyclic guanosine monophosphate (cGMP) during dobutamine infusion and their relationship with hemodynamic parameters in 14 patients with surgically repaired tetralogy of Fallot (TOF). Dobutamine was infused at an initial dose of 5 μg/kg/min and increased by 5 μg/kg/min up to 20 μg/kg/min. The plasma ANP, BNP, and cGMP concentrations were determined before infusion, at the end of each stage, and 15 minutes after discontinuing dobutamine infusion. The plasma concentrations of ANP, BNP, and cGMP were elevated in all patients before dobutamine infusion. The ANP, BNP, and cGMP concentrations decreased in 11 of the 14 patients during dobutamine infusion. In contrast, the plasma ANP and BNP concentrations increased in the remaining 3 patients without a change in the cGMP concentration. The right ventricular pressure and volume were significantly elevated in these patients. The plasma cGMP concentration correlated with the ANP concentration (r= 0.62, p < 0.01) but not the BNP concentration. The plasma ANP concentration during dobutamine infusion correlated with right ventricular systolic pressure (r= 0.71, p < 0.05), mean right atrial pressure (r= 0.29, p < 0.05), and mean pulmonary capillary wedge pressure (r= 0.32, p < 0.05). The BNP concentration correlated with right ventricular volume (r= 0.61, p < 0.05) and systolic pressure (r= 0.46, p < 0.05). In conclusion, rapid changes in ANP, BNP, and cGMP concentrations during dobutamine infusion reflect the changes in atrial and ventricle pressure and volume overload. In surgically repaired TOF, the ANP concentration is affected by right ventricular systolic pressure, right atrial pressure, and pulmonary capillary pressure. Furthermore, the BNP concentration reflects right ventricular pressure and volume overload.     

Atrial natriuretic peptide and other vasoactive hormones during treatment of severe diabetic ketoacidosis in children

Plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), renin activity (PRA), aldosterone, norepinephrine, and cortisol, and renal functions were investigated in nine children with diabetic ketoacidosis. Before therapy, blood glucose concentration was 608.4 +/- 142.2 mg/dL and base excess -21 +/- 1.9 mmol/L. The calculated volume depletion was 2505 +/- 1005 mL/1.73 m2. At the onset of the study, the plasma concentration of ANP (5.3 +/- 1.2 fmol/L) was low, and concentrations of AVP (159 +/- 44 pg/mL), PRA (59 +/- 19 ng angiotensin l/mL/hr), aldosterone (114 +/- 11 ng/dL), norepinephrine (430 +/- 67 pg/mL), and cortisol (33 +/- 2.1 micrograms/dL) were markedly elevated. Fluid replacement raised plasma ANP concentration, which reached physiologic levels on the first day of therapy. PRA, aldosterone, norepinephrine, and cortisol also normalized during the first 24 hours of therapy, whereas AVP remained above the physiologic range at 20.4 +/- 6.8 pg/mL on the third day. Our data indicate that in diabetic ketoacidosis, volume depletion, enhanced sodium excretion, and hyponatremia activated vasoconstrictor and sodium-retaining hormone systems and that secretion of the natriuretic and vasodilator hormone ANP is suppressed. All of these hormonal alterations seem directed at maintaining adequate fluid volume and sodium homeostasis.     

Atrial Natriuretic Peptide and Renin-Aldosterone Relationship in Healthy Newborn Infants

ABSTRACT. Plasma atrial natriuretic peptide (ANP) and aldosterone concentrations, and plasma renin activity (PRA) were measured by radioimmunoassay concurrently in 20 healthy full term infants, in cord blood, at 24 hours after birth and on the 4th day of life. ANP and aldosterone increased significantly at 24 hours and was persistently elevated on the 4th day of life. PRA remained unchanged during the first four days of life. In cord blood, ANP concentrations were correlated with aldosterone concentrations ( r = 0.49, p <0.05) and hematocrit ( r = 0.58, p <0.02). At the 24 hours of life, plasma ANP concentrations were correlated with weight loss observed on the 4th day of life ( r = -0.70, p <0.005), while the percentage changes in plasma aldosterone concentrations were correlated with percentage changes in systolic blood pressure (BP) ( r = 0.49, p <0.05). These findings suggest that during the early newborn period ANP and aldosterone act as an integrated system which has a role in regulation blood pressure and intravascular volume homeostasis.     

Atrial natriuretic peptide and renin-aldosterone relationship in healthy newborn infants.

Plasma atrial natriuretic peptide (ANP) and aldosterone concentrations, and plasma renin activity (PRA) were measured by radioimmunoassay concurrently in 20 healthy full term infants, in cord blood, at 24 hours after birth and on the 4th day of life. ANP and aldosterone increased significantly at 24 hours and was persistently elevated on the 4th day of life. PRA remained unchanged during the first four days of life. In cord blood, ANP concentrations were correlated with aldosterone concentrations (r = 0.49, p less than 0.05) and hematocrit (r = 0.58, p less than 0.02). At the 24 hours of life, plasma ANP concentrations were correlated with weight loss observed on the 4th day of life (r = -0.70, p less than 0.005), while the percentage changes in plasma aldosterone concentrations were correlated with percentage changes in systolic blood pressure (BP) (r = 0.49, p less than 0.05). These findings suggest that during the early newborn period ANP and aldosterone act as an integrated system which has a role in regulation blood pressure and intravascular volume homeostasis.     

The effect of dopamine administration on the activity of the renin-angiotensin-aldosterone system in sick preterm infants

Nine premature infants with birth weight of 1150 to 2500 g and gestational age of 28 to 35 weeks were given dopamine in a dose of 2–4 g/kg/min to treat cardiopulmonary distress.In addition to monitoring of blood gases, blood pressure, acid-base balance, urine flow and urinary sodium excretion, plasma renin activity (PRA) and plasma aldosterone concentration (PA) was also determined prior to and during dopamine therapy.The dopamine-induced increase in urine flow and urinary sodium excretion was associated with a significant increase of PRA from 18.2±5.1 ng/ml/h to 33.0±5.6 ng/ml/h (P<0.025), while PA and blood pressure remained unaltered by dopamine administration.It is suggested that the angiotensin II-stimulated aldosterone production is overridden by the inhibitory effect of dopamine.Abbreviations RAAS renin-angiotensin-aldosterone system - PRA plasma renin activity - PA plasma aldosterone     

The renin-angiotensin-aldosterone system in infancy and childhood in basal conditions and after stimulation

Plasma renin activity (PRA), aldosterone (PA), sodium and potassium concentration were measured in 107 healthy infants and children under basal conditions of normal diet and recumbency. Urinary aldosterone (U_Aldo), sodium and potassium were also measured (n=51). A significant (P<0.001) age-related decrease in PRA (r=-0.67), PA (r=-0.67), and U_Aldo (r=-0.56) was observed, with a striking scatter of values especially in infancy. The renin-angiotensin-aldosterone system (RAAS) was also studied after stimulation by standardised sodium restriction during 4 days, followed by acute postural change (n=40). After salt restriction a rise of PRA and U_Aldo was noted, but a rise in PA could not be demonstrated in children aged 0–6 months. The influence of postural change on the RAAS seems more important in older children. The reported values not only in basal but also in stimulated conditions allow study of the RAAS in diseases such as salt loss and hypertension.Abbreviations PRA plasma renin activity - PA plasma aldosterone - U_Aldo urinary aldosterone - RAAS renin-angiotensin-aldosterone system - U_K urinary potassium - U_Na urinary sodium     

Utility of N-Terminal Brain Natriuretic Peptide Plasma Concentrations in Comparison to Lactate and Troponin in Children with Congenital Heart Disease Following Open-Heart Surgery

We conducted a prospective study in a pediatric cardiac intensive care unit in order to determine the diagnostic value of N-terminal brain natriuretic peptide (N-BNP) plasma concentration in the perioperative care of children with congenital heart disease (CHD). N-BNP plasma concentrations were determined by using a validated enzyme immunoassay. We measured N-BNP the day before surgery and up to 15 days postoperatively in 23 children (age range, 0.25–11 years) undergoing cardiac surgery due to various CHDs. Supply and duration of catecholamines, vasodilators, and respiratory therapy were determined and correlated to N-BNP. In addition, troponin T (TnT) and arterial Lactat (aL) concentrations were measured simultaneously. We found a significant correlation between preoperative and maximal N-BNP levels and dosage of vasodilators (r = 0.41, p < 0.02 and r = 0.83, p < 0.01, respectively). Maximal TnT and aL levels were not correlated to dosage of vasodilators. The dosage and duration of catecholamines, the duration of respiratory therapy, and the plasma concentration of TnT and aL were not correlated to pre- or perioperative N-BNP. Maximal TnT and aL levels were correlated to duration (r = 0.53, p < 0.01 and r = 0.48, p < 0.02) and dosage (r = 0.52, p < 0.02 and r = 0.60, p < 0.01) of catecholamines and duration of respiratory therapy (r = 0.57, p < 0.01 and r = 0.50, p < 0.02). As recent studies show, N-BNP appears to be a powerful neurohumoral indicator of ventricular function and prognosis for guiding therapy in the outpatient department or for discriminating cardiac from noncardiac symptoms. In contrast, the value of N-BNP for guiding perioperative therapy in pediatric cardiac intensive care units is limited.     

Two molecular forms of adrenomedullin in congenital heart disease

To investigate the pathophysiological role of two forms of adrenomedullin (AM), a mature AM (AM-m) and a glycine-extended AM (AM-Gly), in congenital heart disease, we measured plasma levels of AM in patients with cyanotic heart disease, high pulmonary blood flow without pulmonary hypertension (PH), high pulmonary blood flow with PH, Fontan procedure, intracardiac repair without complication, and intracardiac repair with PH and control subjects. Plasma AM-m and AM-Gly were increased only for cyanotic heart disease (2. 5 ± 1.3 pmol/L, p < 0.001; 13.1 ± 6.2 pmol/L, p < 0.05) and intracardiac repair with PH (2.3 ± 1.5 pmol/L, p < 0.01; 13.0 ± 7.0 pmol/L, p < 0.05) compared with control (1.0 ± 1.4 and 8.6 ± 1.3 pmol/L, respectively). They were similarly correlated with mean systemic arterial pressure (r = –0.40 and –0.37 respectively; p < 0.001), mixed venous oxygen saturation (r = –0.60 and –0.50; p < 0.0001), systemic arterial oxygen saturation (SA_sat) (r = –0.56 and –0.46; p < 0.0001), and pulmonary arterial resistance (Rp) (r = 0.41 and 0.38; p < 0.005). Multiple regression analysis revealed that SA_sat and Rp were independently correlated with AM. Interestingly, the venous AM-m level was significantly higher than the arterial AM-m, suggesting that the mature form is extracted in pulmonary circulation, whereas there were no venoarterial differences in AM-Gly. These results suggest that plasma AM-m and AM-Gly are similarly regulated and the main clearance site of AM-m is the lung in patients with congenital heart disease.     

Determinants of hemoglobin concentration in cyanotic heart disease

Summary Children with cyanotic heart disease were studied to determine the effects of chronic hypoxemia, iron stores, and age on hemoglobin. Red cell mean corpuscular volume >90th percentile was found in 72% of children and hemoglobin was higher in this group than in patients with a mean corpuscular volume in the 10–90th percentile or <10th percentile (p<0.05). In children presumed iron sufficient and with oxygen saturation >75%, multiple regression analysis showed that age (p<0.0001) and oxygen saturation (p<0.0001) were associated with hemoglobin. Significant correlations between hemoglobin and oxygen saturation were present for children <2 years (r=–0.50) and 2–11 years (–0.48), but not for patients>11 years. We conclude that variables other than oxygen saturation, including age and iron stores, are important in determining hemoglobin concentration in cyanotic heart disease.     

Plasma renin activity and plasma aldosterone concentration in infants with various sodium intakes

Plasma renin activity (PRA) and plasma aldosterone concentration (PA) were measured in 20 healthy infants 2–12 months of age, after taking a commercial modified cow's milk formula with 8.2 mmol/l sodium for at least five days, and after at least five days on a home-made, undiluted acidified cow's milk formula with 12.6 mmol/l sodium. The mean sodium intakes were 1.20 and 1.87 mmol/kg of body weight per day respectively. The arithmetic means for the corresponding PRA were 6.16 and 1.08 ng/ml·h (difference not significant) and the corresponding arithmetic means for PA were 603 and 355 pg/ml, the difference being highly significant (P<0.01). It is concluded that one has to consider the sodium intake in the milk formula when studying plasma aldosterone in infancy.Supported by a research grant from the Interest Association for Science of the Socialist Republic of Croatia, contract No. V-11/78     

Amino-Terminal Fragment of Pro-Brain Natriuretic Hormone Identifies Functional Impairment and Right Ventricular Overload in Operated Tetralogy of Fallot Patients

To evaluate the relationship between plasma concentration of amino-terminal fragment of pro-brain natriuretic peptide (NT-proBNP), functional capacity, and right ventricular overload in survivors of tetralogy of Fallot (TOF) repair, we prospectively studied 70 operated TOF patients (44 males, 21 ± 1 years old; mean ± SEM) who underwent, during the same day, echocardiography, cardiac magnetic resonance imaging, neurohormonal characterization (plasma NT-proBNP, catecholamines, plasma renin activity, and aldosterone assay), and cardiopulmonary exercise testing. Forty-eight age- and sex-matched healthy volunteers served as the control group. Compared to controls, maximal workload and peak oxygen consumption (VO₂/kg) were lower in operated TOF patients (p < 0.001), whereas NT-proBNP concentration was elevated (p < 0.001). No difference was found among the other neurohormones. In operated TOF patients, NT-proBNP showed a significant positive correlation with right ventricular (RV) end systolic and end diastolic volumes and RV systolic pressure, and it showed a negative correlation with peak VO₂/kg and RV ejection fraction. From multivariable analysis, NT-proBNP concentration was found to be an independent predictor of peak VO₂/kg, RV end systolic volume, and RV systolic pressure. These results show an association among RV overload, decrease in functional capacity, and cardiac natriuretic peptide expression in operated TOF patients. NT-proBNP plasma assay may be a useful tool for diagnostic purposes and for decision making in this setting.     

Cardiovascular effects of hypertransfusion therapy in children with sickle cell anemia

Summary Thirteen children, age 1.9 to 14.8 years with documented sickle cell disease, underwent echocardiographic assessment of cardiac status while on and off periodic hypertransfusion therapy (HTX). Two to three units of washed packed red blood cells were transfused every 2–4 weeks in children with splenic sequestration crises, cerebrovascular accidents (CVA), aseptic necrosis of the femoral head, and miscellaneous complications of sickle cell disease to maintain hemoglobin (Hgb) concentrations of 10g/dl and % sickle hemoglobin (S Hgb) of 20%. This therapy administered over an average duration of 24 months resulted in normalization of left heart chamber enlargement and statistically significant decrease in heart rate, left ventricular mass, and cardiac output. Echocardiographically derived left ventricular function parameters remained normal on and off transfusion therapy. Changes in left ventricular diastolic dimension and cardiac output correlated with changes in % S Hgb (r=0.59,p<0.001; andr =0.54,p<0.001, respectively), and with changes in Hgb concentration (r=–0.78,r=–0.76,p<0.001). Expression of left heart abnormalities as a single composite function (Ydv), using multivariate regression analysis, allowed a comparison of cardiac status of 99 normal black controls, nontransfused sickle cell anemia (SCA) patients, and 13 study patients on and off HTX, and permitted serial assessment of cardiac status on and off treatment over 5 years in a single patient. Normalization of left heart abnormalities in children with sickle cell disease receiving HTX provides further evidence that the major cardiac changes are due to the hypervolemia that results from chronic anemia, and that these changes are reversible with correction of the anemia. Although the specific effect of iron-overload from chronic transfusion therapy was not assessed, we did not find evidence for myocardial dysfunction in children with SCA on or off HTX.     

Value of direct measurement of active renin concentrations in congenital adrenal hyperplasia due to 21-hydroxylase deficiency

In congenital adrenal hyperplasia (CAR) due to 21-hydroxylase deficiency, measurement of plasma renin activity (PRA) has been the method of choice in diagnosing salt loss and in monitoring adequacy of mineralocorticoid replacement therapy. Due to methodological problems in PRA determinations, direct immunoradiometric assays for the measurement of active renin concentration have been developed. We measured PRA and active renin concentrations simultaneously in 39 patients with CAH (30 salt-wasting, 9 simple virilizing) to evaluate the potential role of this new method in the management of this disease. PRA was determined with an enzymatic assay (sample volume: 2 × 1000 l plasma), active renin concentration with a direct immunoradiometric assay (sample volume: 2 × 200 l plasma or serum). We found a highly significant correlation between active renin and PRA in our patients (P < 0.001), as previously shown in healthy subjects. Active renin was as reliable as PRA to assess the quality of mineralocorticoid replacement.     

Right Ventricular Volume Measurements in Ventilated Preterm Neonates

Pulmonary hypertension is associated with worse perinatal outcomes in infants with respiratory disorders. In these infants, right ventricular dysfunction may result in poor pulmonary blood flow. The objective of this study was to follow changes in right ventricular volumes during the first 2 days of life in infants with respiratory distress syndrome. Serial echocardiographic examinations were performed on days 0–2 on infants ventilated for respiratory distress syndrome. Two-dimensional echocardiography with the ellipsoid approximation was used to calculate systolic and diastolic volumes. In 17 ventilated preterm infants, right ventricular volumes were significantly lower on day 2 compared with day 0 and decreased from a median (interquartile range) end systolic volume of 0.80 ml/kg (0.66–0.91 ml/kg) to 0.45 ml/kg (0.39–0.54 ml/kg) (p < 0.001). End diastolic volume decreased from a median (interquartile range) of 1.54 ml/kg (1.44–1.65 ml/kg) to 1.30 ml/kg (1.22–1.60 ml/kg) (p = 0.039). Right ventricular ejection fraction increased from a median (interquartile range) of 0.48 ml/kg (0.44–0.56 ml/kg) to 0.62 ml/kg (0.58–0.71 ml/kg) during the same period (p < 0.001), as did right ventricular output from a median (interquartile range) 120 ml/kg/min (96–125 ml/kg/min) to 140 ml/kg/min (113–168 ml/kg/min) (p = 0.044). Right ventricular volume decreases during the first 2 days of life in ventilated preterm infants. However, right ventricular performance is maintained.     

Corticosterone methyl oxidase type II deficiency: a cause of failure to thrive and recurrent dehydration in early infancy

Corticosterone methyl oxidase type II (CMO II) deficiency is an uncommon cause of salt-wasting in infancy. We describe a boy who presented with recurrent dehydration and severe failure to thrive in the first 3 months of life, associated with mild hyponatraemia (serum Na⁺ 127–132 mEq/l) and hyperkalaemia (serum K⁺ 5.3–5.9 mEq/l). The diagnosis was suggested by an elevated plasma renin activity (PRA): serum aldosterone ratio, and subsequently confirmed by an elevated serum 18-hydroxycorticosterone: aldosterone ratio. Treatment with 9-fluorohydroxycortisone normalized growth parameters and PRA levels. CMO II deficiency should be considered in infants with recurrent dehydration and failure to thrive, even when serum sodium and potassium levels are not strikingly abnormal.     

Hormonal background of the hypertension and fluid derangements associated with adrenocorticotrophic hormone treatment of infants

We studied the hormonal background of the fluid derangements and arterial hypertension associated with adrenocorticotrophic hormone (ACTH) treatment for infantile spasms in ten infants aged 5–22 months. They received a 6 week course of (carboxymethyl-cellulose-)ACTH: 80IU at 0800 hours daily in weeks 1–3, then tapering, and termination at the end of week 6. The infants showed large, variable increases in 24 h urine cortisol during treatment. The mean plasma cortisol concentration (24 h after ACTH injection) was not significantly increased, but was correlated with the relative dose of ACTH. The mean plasma aldosterone concentration decreased. No significant change occurred in plasma renin activity (PRA), or in the concentrations of renin substrate (RS) or arginine vasopressin (AVP). Seven infants developed arterial hypertension, which was severe in three. This severe hypertension was associated with the highest relative ACTH doses and the highest plasma RS and cortisol concentrations. In the group as a whole, systolic blood pressure correlated with plasma RS and cortisol concentrations, but not with the other parameters. At the end of treatment urine and plasma cortisol dropped below the pretreatment levels and stayed low for >2 weeks. There was a sharp peak in PRA and plasma aldosterone concentration, and a decrease in plasma RS. Plasma AVP levels dropped markedly. The mean body weight increased sharply and urine flow decreased. Mean plasma electrolyte levels remained unaltered. The danger at termination of ACTH treatment appears to be associated with a sudden transition from hypercortisolism to hypocortisolism, activation of the renin-angiotensin-aldosterone axis, and suppression of AVP secretion.Abbreviations ACTH adrenocorticotrophic hormone - AVP arginine vasopressin - PRA plasma renin activity - RS renin substrate - 17-KGS 17-ketogenic steroids Dedicated to Professor Walter Teller on the occasion of his 60th birthday     

Effects of dopamine infusion on plasma catecholamines in preterm and term newborn infants

Newborn infants (21 preterm and 13 term) received dopamine infusions at a low (2.5–3.4 g/kg per min) and/or high (5–10 g/kg per min) infusion rate and changes in plasma catecholamines were monitored. The mean baseline values for dopamine, noradrenaline and adrenaline were between 240 and 560, 125 and 144 and 62 and 82 pg/ml, respectively. During low-rate infusion of dopamine, there was a significant increase in plasma dopamine (20–100fold), noradrenaline (three- to five-fold) and adrenaline (threefold). Administration of dopamine at the high rate resulted in an even larger increase in the plasma catecholamines (dopamine, 100–300fold; noradrenaline, seven- to eightfold; adrenaline, four- to sixfold). In a double-log plot, there was a highly significant correlation between the plasma concentrations of dopamine and noradrenaline (r=0.77;P<0.001). In conclusion, infusion of dopamine in term and preterm newborn infants is accompanied by an enhanced sympatho-adrenal tone which may contribute to the cardiovascular effects of dopamine in these patients.     

Two decades of acute hematogenous osteomyelitis in children: are there any changes?

Our purpose was to compare the clinical course of acute hematogenous osteomyelitis (AHO) 20 years ago and today in the Department of Paediatric Surgery, Kaunas Medical University Hospital, Lithuania. Retrospective data analysis from patients aged 1–16 years with confirmed diagnosis of AHO was performed. The data were collected from 1982 to 2003. The incidence of AHO per year for 1,00,000 children (0–16 years) was analyzed for that period. The patients were divided into two groups—group A, treated in 1982–1983, and group B, treated in 2002–2003. The number of patients, patient age, duration of illness, complications, and length of hospital stay were compared using statistical methods for nonparametric data analysis (Mann–Whitney U test, chi-square criterion). Linear regression was used for incidence analysis. Population data were obtained from the Lithuanian Statistics Department. From 1982–2003, 758 patients were treated. The incidence of AHO increased from 1982. There was no statistically significant difference between the periods 1982–1983 and 2002–2003 in median patient age (10.36 and 10.72 years, respectively), in gender proportion (20.4% and 29.8% of the cases were girls), or in median duration of symptoms until admission (4 days and 3 days, respectively, p=0.058). Median hospital stay and duration of antibiotic therapy were longer in the period 1982–1983 (50 days and 43 days) than during 2002–2003 (29 days and 29 days). The differences in frequency of positive blood cultures (36.4% in group A and 64.9% in group B, p=0.046) and frequency of periosteal abscess (40.8% in group A and 19.3% in group B, p=0.015) were statistically significant. An increase in AHO incidence is seen when comparing contemporary data and the data from two decades ago, but nowadays the clinical course is less complicated and is marked by shorter hospital stays and shorter duration of antibiotic therapy.     

Ammonium chloride metabolic acidosis and the activity of renin-angiotensin-aldosterone system in children

The present study was undertaken to assess the effects of acute metabolic acidosis on the activity of the renin-angiotensin-aldosterone system in 12 children with a mean age of 8.9 years who underwent NH₄Cl loading test. Ammonium chloride was given in a dose of 0.15 g/kg per day for 3 consecutive days to evaluate renal acidification. Prior to and following NH₄Cl administration blood acid-base parameters, plasma and urine electrolytes, creatinine and aldosterone concentrations as well as plasma renin activity (PRA), urine flow rate and net H⁺ excretion were measured. Ammonium chloride administration significantly depressed blood pH (P<0.05), bicarbonate (P<0.01) and base excess (P<0.01) and resulted in a slight, but significant elevation of plasma potassium concentration (P<0.05). Furthermore, NH₄Cl ingestion induced a marked increase in urine flow rate (P<0.01) and urinary sodium, potassium and chloride excretion (P<0.01). In response to NH₄Cl metabolic acidosis, PRA doubled (4.72±1.18 vs 8.13±1.02 ng/ml per hour,P0.05) and there was a nearly fourfold increase in plasma aldosterone level (0.49±0.12 vs 1.52±0.24 ng/ml,P<0.01) and in urinary aldosterone excretion (19.2±4.3 vs 71.8±13.8 g/day,P<0.01). The elevated aldosterone production observed in this study is assumed to be mediated by the combined effect of sodium and water diuresis-related increased PRA, hyperkalaemia and the direct stimulation of adrenal steroidogenesis by metabolic acidosis.     

Plasma Nitric Oxide Products Correlate with Cardiac Index of Congenital Heart Disease

We wished to determine the relationship between circulating levels of nitric oxide (NO) and cardiac index (CI) in children with congenital heart diseases. We measured the plasma levels of nitrate/nitrite (NO _x ), the stable end products of NO production as well as tumor necrosis factor-α (TNF-α), atrial natriuretic peptide (ANP), and brain natriuretic peptide in relation to various parameters determined simultaneously. The plasma NO _x levels correlated negatively with CI (r=−0.541, p < 0.05). No correlation was observed between NO _x and cardiac output. TNF-α correlated with NO _x levels (r= 0.593, p < 0.005) but not with either CI or cardiac output. Plasma levels of ANP and TNF-α were higher in atrial septal defect than those in the control group (p < 0.001 and p < 0.05, respectively). Elevated plasma NO _x could explain the increased basal release of endothelial NO due to high pulmonary blood flow. Plasma NO _x correlate negatively with CI in young patients with left-to-right shunt congenital heart diseases.