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 Atrial Pressures in Newborns with Transposition of the Great Arteries

ABSTRACT. The relation of atrial pressure to atrial plasma concentration of atrial natriuretic peptide (ANP) was studied in four newborns undergoing catheterization because of transposition of the great arteries. In three patients, mean left atrial pressure clearly exceeded right atrial pressure (12±7 vs. 2±3 mmHg; mean ±SD). In one patient mean atrial pressures were identical (4 mmHg). In all patients the ANP concentration in the left atrium exceeded that of the right (833±464 vs. 415±366 pg/ml; mean ±SD). There was a significant ( r =0.97; p < 0.01) correlation between pressure and ANP concentration in the left atria. In the right atria, no linear correlation existed between pressure and ANP concentration. ANP concentration in the left atrium decreased after a lowering of the left atrial pressure by atrial septostomy. In these patients, the left atrium seems to be the main source of circulating ANP.     

Changes in Plasma Concentrations of Atrial Natriuretic Peptide during Exchange Transfusion in Premature Infants

ABSTRACT. Plasma concentrations of atrial natriuretic peptide (ANP) and hemodynamic parameters were investigated in five premature infants undergoing exchange transfusion. Baseline values of ANP were 51.7 ± 21.2 fmol/ml. Volume depletion by withdrawal of 10 ml blood did not cause changes in systolic blood pressure (79.4 ± 4.3 vs. 71.4 ± 5.6 mmHg) and heart rate (115 ± 5.2 vs. 115 ± 2.4 b/min). ANP levels in plasma remained unaltered (53.4 ± 24.9 fmol/ml). Replacement of 10 ml blood increased central venous pressure by 33% and ANP concentration in the plasma by nearly 30%, while heart rate and blood pressure remained unchanged. Our data indicate that the heart of the premature infant responded to acute blood replacement with increased ANP-release, while blood removal appeared not to influence hormone regulation.     

Relationship between Plasma Atrial Natriuretic Peptide Concentrations and Cardio-Thoracic Ratio during the Early Neonatal Period

ABSTRACT. Twenty-seven neonates were examined at 2.6±1.5 hours of age (stage 1) and 21 ±4.9 hours of age (stage 2) to clarify the relationship between cardio-thoracic ratio (CTR) on chest roentgenograms and plasma atrial natriuretic peptide (ANP) concentration. Among 22 infants who showed elevated plasma ANP, 14 had gained body weight (group A), while 8 other infants had lost weight (group B) at stage 2. The remaining 5 infants had decreased plasma ANP concentrations combined with weight loss at stage 2 (group C). All infants of group B had a patent ductus arteriosus. The plasma ANP concentration and CTR of groups A and B increased during the study period, while those of group C decreased. A linear relation was found between plasma ANP concentration and CTR in all cases (p<0.02). This study indicates that increased plasma levels of ANP are associated with an increased CTR.     

Plasma Concentrations of Atrial Natriuretic Peptide in Children with Persistent Hypertension

Plasma concentrations of human atrial natriuretic peptide (hANP) were determined in children with persistent hypertension and in age-matched normotensive controls. We studied 40 children 6–7 years of age (Group A), and 74 children 13–14 years of age (Group B). There was no significant difference in plasma hANP concentration between hypertensives and normotensives in group A. In group B, the plasma hANP concentration in hypertensives (86.5 ±44.9 pg/ml: mean±SD) was significantly higher than in normotensives (58.8±40.4 pg/ml) (p <0.01). In group B, 24-hour urinary excretion of sodium and fractional excretion of sodium were not significantly different between hypertensives and normotensives. The plasma hANP correlated significantly with the fractional excretion of sodium (p<0.05)and the 24-hour urinary excretion of sodium (p<0.01) in normotensives. No such correlation was evident in the case of the hypertensives. The pathogenesis of increased plasma hANP concentration in older children with persistent hypertension remains to be investigated. In regard to the effects of hANP on renal function, hANP may contribute to the regulation of sodium handling in normotensive adolescents, whereas other regulatory mechanisms need to be considered in the case of hypertensives.     

The Physiological and Biological Significances of Human Atrial Natriuretic Peptide in Neonates

ABSTRACT. The purpose of our study was to analyze the physiological and biological significances of the high human atrial natriuretic peptide (hANP) levels during early post-natal period. The absolute values or changes of plasma hANP concentrations did not correlate with the absolute values or changes of body weight, blood pressure, urinary sodium/creatinine and urinary aldosterone/creatinine ratios. Gel permeation chromatography of samples from two neonates revealed the presence of two molecular forms of hANP, α and β, both in the plasma and urine. In the plasma, the β-hANP was predominant on the 3rd day of life and the α-hANP on the 6th day of life. The change from one form to another was independent of the absolute value of hANP. We obtained no evidence suggestive of a physiological role of the high plasma hANP concentration during the early post-natal period. However, because of biological differences between these two fractions, their distribution must be taken into account when attempting to interpret the high hANP values observed in neonates.     

窒息新生儿血浆N端脑钠肽原水平的变化

目的　探讨窒息新生儿血浆N端脑钠肽原 (NT proBNP)水平的变化 ,评价血浆NT proBNP对新生儿窒息并心功能障碍的临床意义 ,并了解新生儿血浆NT proBNP水平与日龄的关系。方法　采用竞争性酶免疫法 (EIA)测定 41例健康新生儿 (对照组 )及 3 3例窒息新生儿 (窒息组 )血浆NT proBNP水平 ,同时测定窒息组血浆肌酸激酶同工酶 (CK MB)、乳酸脱氢酶1 (LDH1 )及肌钙蛋白I(CTnI)水平。结果　对照组 <14d的新生儿 (n =2 8)血浆NT proBNP水平较高 [(2 479.82± 14 0 0 .0 1)fmol/mL] ,而 14d后 (n =13 )降为 (3 71.5 4± 14 7.40 )fmol/mL ,新生儿血浆NT proBNP水平与月龄呈显著负相关 (r =-0 .73 5　P <0 .0 0 0 1)。窒息组出生 3d内血浆NT proBNP水平显著高于对照组中出生 3d内者 (n =15 )的水平 :(3 92 4± 10 3 0 )fmol/mL比 (3 192± 14 86)fmol/mL(t=1.979　P <0 .0 5 ) ;重度窒息者 (n =10 )显著高于轻度窒息者 (n =2 3 ) :(4 2 2 8± 10 87)fmol/mL比 (3 5 40± 992 )fmol/mL(t=3 .17　P <0 .0 1)。多元线形回归分析揭示 :LDH1 和CTnI对血浆NT proBNP水平的影响具有统计学意义。回归方程为 :NT proBNP =12 0 2 + 1.46×LDH1 + 40 9×CTnI(F =40 .7　P <0 .0 0 0 1)。结论　窒息新生儿血浆NT proBNP水平能反     

急性心力衰竭患儿血浆脑钠素及心钠素水平的变化

目的探讨急性心力衰竭患儿血浆脑钠素(BNP)及心钠素(ANP)水平变化及其意义。方法选择不同病因的充血性心力衰竭(CHF)患儿46例及肺炎患儿40例、先天性心脏病患儿31例、健康儿童40例,应用酶联免疫吸附法分别检测血浆BNP及ANP水平,用多普勒超声心动图测量心力衰竭患儿心衰期及恢复期心脏指数(CI)及左室射血分数(LVEF)。结果CHF患儿心衰前期BNP即开始升高,心衰时达高峰(P<0.001),恢复期BNP水平渐下降,但仍高于正常值(P<0.001);心衰时心脏CI、LVEF均明显下降(P<0.01);CHF患儿心衰时升高的BNP水平与CI、LVEF均呈明显负相关(r=-0.61,0.79P均<0.05);同时测定的ANP动态变化趋势与BNP类似;CHF患儿心衰时的BNP/ANP比值远远高于正常对照;心衰时BNP与ANP异常率比较有显著差异(P<0.05);心衰时BNP水平与LVEF、CI值相关性优于ANP。结论CHF患儿血清BNP及ANP水平明显升高.且与心衰程度关系密切,BNP反映心脏功能改变较ANP更敏感,更具有特异性。     

Atrial Natriuretic Peptide and Extracellular Volume Contraction after Birth

ABSTRACT. Plasma concentrations of atrial natriuretic peptide (ANP) were measured in full-term newborns immediately after birth and on the 3rd, 5th, 7th and 10th day of life. The ANP concentrations were within the normal range in the first hours of life. Plasma concentrations of ANP had increased significantly on the 3rd and 5th day of life, while body weight decreased continuously. After the 5th day of life ANP concentration decreased continuously reaching its minimum on the 10th day whereas body weight increased. The mechanism behind ANP release shortly after birth is not known. The increase in ANP concentration in plasma may however induce changes in body fluid compartments shortly after birth which would result in physiological weight loss.     

Plasma Atrial Natriuretic Polypeptide Concentration in Healthy Children from Birth to Adolescence

ABSTRACT. We measured plasma atrial natriuretic polypeptide concentrations in the umbilical artery and vein, and peripheral veins of healthy children from birth to adolescence to establish the normal range. The plasma atrial natriuretic polypeptide concentration in the umbilical artery (mean±SD, 51.0±21.4 fmol/ml) was significantly higher than that in the umbilical vein (18.1±13.5 fmol/ml) in neonates after vaginal delivery. Also neonates aged 5 days or less had a significantly high concentration in the peripheral vein (60.7±29.4 fmol/ml). There was no significant difference in atrial natriuretic polypeptide concentrations in the peripheral veins between older children and adults. The concentrations in children aged more than 5 days and adults aged 20–34 years were 14.4±7.4 fmol/ml and 10.0±4.8 fmol/ml, respectively. However, the atrial natriuretic polypeptide concentration in the umbilical artery was not increased in three neonates delivered by caesarean section although they had a high concentration in the peripheral vein 24 hours after birth.     

Role of Atrial Natriuretic Peptide in the Diuresis of a Newborn Infant with the Syndrome of Inappropriate Antidiuretic Hormone Secretion

ABSTRACT. A fullterm infant had fetal distress and stained amnion. He underwent an exchange blood transfusion at 12 hours after birth because of hyperbilirubinemia. He developed oliguria combined with high urine osmolality during the first 27 hours of life despite normal creatinine clearance. The diagnosis of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was made on the basis of high urine osmolality, low plasma osmolality and elevated plasma arginine vasopressin (AVP) concentration. We determined the plasma atrial natriuretic peptide (ANP) concentration for the first 4 days of life. After 27 hours after birth, urine volume increased while plasma AVP concentration remained high. On the other hand, plasma ANP concentration gradually increased after 27 hours of life. We speculate that ANP may play an important role in producing the spontaneous diuresis in the newborn infant with SIADH.     

Influence of Dopamine on Atrial Natriuretic Peptide Level in Premature Infants

ABSTRACT. The role of dopamine (DA) in the activation and/or release of atrial natriuretic peptide (ANP) was investigated in 11 premature infants during the early postnatal period. Mean plasma concentration of ANP and free DA level before DA infusion was 252.6±210 fmol/ml, and 0.4±0.2 ng/ml, respectively. DA infusion in a dose of 2μg/kg/min caused a rise in plasma free DA level to 59.7±21.5 ng/ml and a significant increase in GFR, diuresis, sodium excretion and fractional sodium excretion. The plasma concentration of ANP, however, remained unchanged (252.6±210.0 vs. 213±143.0 fmol/ml). Thus, our data failed to demonstrate a stimulatory effect of DA on ANP release in premature infants. The role of the high plasma concentration of ANP in preterm neonates immediately after birth has to be clarified.     

慢性充血性心力衰竭患儿血浆儿茶酚胺、心钠素水平的意义

目的探讨慢性充血性心力衰竭（CHF）患儿血浆儿茶酚胺（CA）[包括肾上腺素（E）、去甲肾上腺素（NE）]、心钠素（ANP）水平变化及其与心脏左室功能的关系。方法选择CHF患儿及正常对照组各35例，测定其血浆NE、E及ANP水平，检测左室射血分数（LVEF）。结果1．CHF组治疗前血浆NE、E、ANP水平显著高于正常对照组，二组比较差异有显著性（Pa〈0．01）。2．CHF组治疗前显著高于抗心力衰竭综合治疗心力衰竭好转后血浆NE、E、ANP水平，二组比较差异有显著性（Pa〈0．01）。3．CHF组治疗后血浆NE、E、ANP水平显著高于正常对照组，二组比较差异有统计学意义（Pa〈0．05）。4．CHF组心功能越差，血浆NE、E、ANP升高越明显，差异有显著性（P〈0．01）。5．以35例CHF患儿血浆NE、E、ANP为自变量，LVEF为应变量作直线相关分析，显示CHF组血浆NE、E、ANP与LVEF呈显著负相关。结论CA、ANP水平与CHF程度密切相关，心功能下降可能与CA、ANP水平过度生成有关，其可作为评价CHF的指标之一。     

一氧化碳对大鼠心室组织心钠素分泌的影响

目的探讨一氧化碳(CO)在大鼠心室组织孵育液中对心钠素(ANP)分泌的影响。方法将正常Wistar大鼠的左、右心室分别分为对照组(未加药)和血红素组(孵育时加入血红素,终浓度10-4mol/L),每组各12例,用Krebs液作为孵育液,放入37℃恒温水浴箱中振荡孵育4 h,用放射免疫法测定孵育液中ANP含量。结果与对照组比较,血红素组大鼠左心室[(9.72±3.59)ng/(g.wet tissue)vs(52.05±31.65)ng/(g.wet tissue),P<0.01]和右心室[(5.55±3.98)ng/(g.wet tissue)vs(62.73±41.66)ng/(g.wet tissue),P<0.01]组织孵育液中ANP含量明显降低。对照组大鼠左右心室组织孵育液ANP含量没有明显差异;血红素组中,大鼠右心室组织孵育液中ANP含量明显低于左心室组织孵育液中ANP含量[(5.55±3.98)ng/(g.wet tissue)vs(9.72±3.95)ng/(g.wet tissue),P<0.05]。结论CO可抑制大鼠左右心室组织孵育液ANP含量,且CO可能对右心室组织孵育液ANP含量的抑制作用大于对左心室组织孵育液ANP含量的抑制作用。     

缺氧缺血性脑病新生儿内皮素、降钙素基因相关肽、心钠素及血清钠、钙的变化

目的探讨HIE患儿血浆内皮素(ET)、降钙素基因相关肽(CGRP)及心钠素(ANP)的变化及其临床意义。方法应用放射免疫分析法和离子交换法测定46例HIE和26例正常新生儿的血浆ET、CGRP、ANP和血清钠、钙水平。结果HIE组急性期血浆ET、CGRP和ANP水平明显高于对照组及恢复期组(P均<0.001));病情越重,ET、CGRP和ANP水平越高,恢复期血浆ET、CGRP和ANP水平渐下降,中重度组下降的幅度更为缓慢。HIE中重度组血钠水平明显低于对照组(P<0.05);不同程度HIE组血钙水平均明显低于对照组,差异显著(P<0.01)。HIE组治疗前后血浆ET与CGRP、ANP水平呈直线正相关,急性期血浆ET与血钙、血浆ANP与血钠之间无明显相关性(P均>0.05)。结论血浆ET、CGRP和ANP共同参与HIE发病机制及病理过程,其动态变化有助于病情判断、疗效评价及预后评估。     

Correlation of Plasma B-Type Natriuretic Peptide with Shunt Severity in Patients with Atrial or Ventricular Septal Defect

The goal of this study was to test the utility of bedside plasma concentration of B-type natriuretic peptide (BNP) assay as a screen for large shunts in pediatric patients with atrial septal defects (ASDs) and ventricular septal defects (VSDs). Thirty-five children at a mean age of 70 ± 129 weeks with ASD or VSD were included in the study. Nine patients had VSD and 26 had ASD. Plasma BNP values were compared with the Q _p/Q _s ratios derived from quantitative Doppler flow measurements. Mean BNP was 29 ± 42 pg/ml, with a range between <5 pg/ml and 208 pg/ml. Sixteen patients had Q _p/Q _s values >1.5 and 19 had values <1.5. The difference of mean BNP in these patient groups was statistically significant (45 ± 56 vs 14 ± 17, p = 0.03). BNP was positively correlated with shunt significance. Receiver operating characteristic curve analysis revealed a sensitivity of 69% and a specificity of 79% at a plasma BNP cut-off level of ≥20 pg/ml. Bedside measurement of BNP correlates with magnitude of ASD and VSD in children. BNP can provide information for the management of children with ASD or VSD. It can be used as part of the evaluation of a child with a preliminary diagnosis of a congenital defect.     

Plasma Concentrations of N-Terminal Brain Natriuretic Peptide in Healthy Children, Adolescents, and Young Adults: Effect of Age and Gender

Children with congenital heart disease need adequate diagnostic classification regarding their cardiovascular status (CVS). N-terminal brain natriuretic peptide (N-BNP) plasma concentration indicates dysfunction of the cardiovascular system and guides decisions concerning treatment and prognosis. Reference values are established for adults, with age-dependent increasing values and higher values in women. To avoid misclassification concerning the CVS, a large group of healthy children and adolescents can be used show the relationship between gender, age, and N-BNP and these can serve as reference values. N-BNP was measured in 434 healthy subjects (240 female and 194 male) with ages ranging from 0 to 32 years without any cardiovascular disease or renal or hepatic impairment. Measurements were performed with an electrochemiluminescence immunoassay from Roche Diagnostics. Mean N-BNP decreased from 12.6 fmol/ml (0–9 years; n = 79) to 9.41 fmol/ml (10–14 years; n = 154) and in adolescents from 6.1 (15–19 years; n = 99) to 4.8 fmol/ml (>19 years; n = 102) in adults (p < 0.05). Mean N-BNP concerning gender did not differ in any age group younger than 19 years. In contrast, the adult female group had 78% higher N-BNP compared to the male group (p < 0.05). There was a significant peak in N-BNP at the age of 12–14 years. This study shows that reference values for N-BNP differed profoundly in children compared to adults and were up to 260% higher in children without any gender difference. Therefore, these reference values will help to avoid CVS misclassification in children for the biomarker N-BNP.     

心力衰竭婴儿血浆脑利钠肽水平变化的意义

目的探讨心力衰竭(HF)婴儿血浆脑利钠肽(BNP)水平变化与HF严重程度的关系,及其对婴儿HF诊断、心功能分级和疗效监测的临床意义。方法随机选取2006年10月-2008年9月在本院儿科住院的HF婴儿30例为研究对象,并根据Ross分级标准将其分成轻、中、重度3组。在HF纠正前后收集HF婴儿血浆,检测BNP水平。随机选取本院体检中心健康婴儿30例为健康对照组。健康对照组和HF组婴儿血浆BNP水平测定采用化学发光微粒子免疫分析法;采用M型超声心动图测量HF组婴儿的左心室射血分数(LVEF),并分析血浆BNP水平与LVEF的相关性。结果HF婴儿血浆BNP水平[(629.17±508.53)×10-6ng.L-1]显著高于健康对照组[(65.13±31.98)×10-6ng.L-1](t=4.884,P<0.05)。HF程度越重,血浆BNP水平升高越显著,血浆BNP水平与LVEF呈负相关(r=-0.508,P<0.05),与心功能分级呈正相关(r=0.527,P<0.01)。HF纠正后血浆BNP水平[(105.02±57.81)×10-6ng.L-1]显著低于HF纠正前[(629.17±508.53)×10-6ng...     

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.     

B-Type Natriuretic Peptide Levels in Congenital Heart Disease

The objective of this study was to evaluate the potential role of B-type natriuretic peptide (BNP) levels in children with congenital heart disease undergoing cardiac catheterization. Measurement of plasma BNP concentration has been shown to be useful in the diagnosis, risk stratification, and management of adult patients with congestive heart failure, but little is known about the role of BNP in children with structural congenital heart disease. We measured plasma BNP levels using the Triage BNP test in patients with congenital heart disease referred for diagnostic or interventional cardiac catheterization. Plasma BNP concentration was measured in 96 children and 11 adults 19 years old (7.9 ± 8.3 years) undergoing heart catheterization for underlying congenital heart disease. BNP levels ranged from <5 to >1300 pg/ml, with a median BNP concentration of 19.0 pg/ml. Baseline BNP concentrations were >100.0 pg/ml on 19 occasions in 17 patients. The pressure difference between the left ventricle and ascending aorta was 10–110 mmHg in 21 patients. BNP concentrations for this cohort ranged from <5.0 to 1060.0 pg/ml and correlated with the degree of left ventricular outflow obstruction (correlation coefficient, 0.661; p = 0.001). This study suggests that with additional research, BNP concentration may prove to be a useful clinical tool in managing children and adults with congenital heart disease.