Comparison of plasma atrial natriuretic peptide levels in healthy children from birth to adolescence and in children with cardiac diseases

An age-related dependence of plasma ANP levels was studied in 163 healthy children (94 boys, 69 girls) between the ages of day 1 and 16 yr. In neonates during the first 2-4 days of life, significantly higher plasma ANP plasma levels (range 129-356 pg/ml, mean 227) were found compared with older infants and children (p less than 0.001). Beyond the neonatal period through adolescence no significant difference in ANP concentrations could be found between the various age groups. Plasma ANP levels ranged between 2 and 109 pg/ml (mean 47) for all age groups after the newborn period. ANP levels were also determined in 15 adult volunteers and in arterial and venous cord blood of 16 healthy newborns, and concentrations were similar to those found in children. In addition, plasma ANP levels were measured in 40 children with various cardiac diseases; 22 of 40 patients exhibited ANP levels above the upper normal range seen in control children. Of these 22 patients all except two children revealed clinical signs of heart failure. In contrast 15 of 17 children without heart failure showed plasma ANP levels within the range of control children. ANP plasma levels ranged between 93 and 967 pg/ml (mean 284) in patients with heart failure and between 15 and 118 pg/ml (mean 57) in patients without heart failure, respectively. Increased ANP levels in neonates and cardiac patients may result from increased atrial distention and reflect a compensatory mechanism to improve cardiac function by reducing pre- and afterload.     

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.     

Role of atrial natriuretic peptide in sodium homeostasis in premature infants

To examine the possible involvement of atrial natriuretic peptide (ANP) in sodium homeostasis in premature infants, two groups of low birth weight infants with different dietary sodium regimens were studied. Sodium balance and plasma concentration of ANP were measured at weekly intervals for 5 weeks. At 1 week of age the study was started by dividing infants into two groups, group 1 with low and group 2 with increased sodium intake. Mean plasma concentrations of ANP were 47.7 +/- 7.6 and 51.4 +/- 9.5 fmol/ml, respectively. A steady decrease in plasma ANP concentration to 18.8 +/- 2.9 fmol/ml was observed in infants with sodium intake 1.5 mmol/kg/d (group 1), which was related to the decrease in serum sodium concentration in this group. In contrast, supplementation with NaCl 4.6 mmol/kg/d (group 2) was associated with a 30% increase in plasma ANP concentration, significantly different (P less than 0.025) from that in infants not given supplement, and was also higher than the values in full-term neonates. Our data suggest that altered sodium homeostasis induces regulatory changes in plasma ANP levels. ANP may provide a sensitive and important hormonal system for the control of sodium balance, even in premature neonates.     

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.     

Relationship between plasma atrial natriuretic peptide concentrations and cardio-thoracic ratio during the early neonatal period

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 less than 0.02). This study indicates that increased plasma levels of ANP are associated with an increased CTR.     

Atrial natriuretic peptide, cyclic guanosine monophosphate and sodium excretion during postnatal adaptation in male infants below 34 weeks gestation with severe respiratory distress syndrome.

The role of atrial natriuretic peptide (ANP), in the perinatal period, is at present unclear. In adults urinary cyclic guanosine monophosphate (cGMP) is considered an index of the biological activity of plasma ANP. The aim of this study was to determine the relationship between plasma ANP, cGMP excretion (cGMPex) and sodium excretion (Naex) in preterm infants in the first days after birth. Sequential, 4 hourly, measurements of plasma ANP, cGMPex and Naex were made in 12 male neonates of median gestational age 27 weeks (range 25-33) and median birth weight 0.981 kg (range 0.635-2.029) over a median period of 5.2 days (range 2.3-10). The ratios of cGMPex to ANP and of Naex to cGMPex were each plotted against postnatal age. The ratio of cGMPex to ANP increased ten fold in the first 3-4 days after birth but then remained relatively constant; the ratio of Naex to cGMPex showed a steady increase from birth. We conclude that, in extremely immature infants, renal sodium loss in response to cGMP increases rapidly during the first 10 days after birth. In addition, after 3-4 days from birth, plasma ANP ia associated with a constant proportionate rate of cGMP excretion though, as the plateau ratio of cGMPex to ANP varied widely between babies, cGMPex cannot be used to predict plasma ANP in cross sectional studies. These changes may reflect postnatal adaptation and/or maturation of both ANP receptors and cGMP mediated cascades. In the immediate postnatal period, plasma ANP may also have a non-renal role.     

Atrial natriuretic peptide in the preterm infant. Lack of correlation with natriuresis and diuresis

We assessed the relation of atrial natriuretic peptide (ANP) to renal function on postnatal day 2 and day 5 in preterm infants. Plasma ANP concentration was measured by radioimmunoassay in two groups of preterm infants: group 1, gestational age less than 30 weeks, n = 10; and group 2, gestational age 30-34 weeks, n = 11. The identity of the immunoreactivity as ANP-28 was confirmed by HPLC. Plasma ANP was significantly higher in group 1 than in group 2 on day 2 and day 5 (p < 0.01) and ANP concentration decreased by day 5 in both groups (group 1, p < 0.01; group 2, p < 0.02). The results showed no correlation between plasma ANP concentration and urinary sodium excretion or creatinine clearance, which may be due to a blunted renal response to ANP, but other factors may be involved also. We conclude that preterm infants are able to release large amounts of ANP, but a high plasma ANP concentration does not correlate directly with renal regulation of sodium and water balance.     

Atrial natriuretic peptide during early human development.

The present review summarizes current and new knowledge on the role of atrial natriuretic peptide (ANP) during early human development. The significance of plasma ANP concentrations in relation to atrial size and ductus flow in preterm and full-term infants is emphasized. Evidence from the literature suggesting the importance of ANP in pulmonary hypertension of the newborn is explored. New information is included on the ontogeny of the renal ANP receptor system in the rat. Integrating the currently available knowledge, a hypothesis on the role of ANP in the circulatory adaptation of the human neonate to extrauterine life is presented.     

Urodilatin and atrial natriuretic peptide are present in the urine of healthy neonates and young infants.

Urine sampling has been proposed as noninvasive monitoring of plasma atrial natriuretic peptide (ANP) in neonates, assuming urine contains only filtered plasma ANP. Recently, urodilatin, another natriuretic peptide, which is cross-reactive to ANP in the ANP radioimmunoassay (ANP-RIA), has been isolated from the urine of adults. We studied the urine of healthy term neonates and young infants for the presence of urodilatin. In all urine samples, we found three peaks of ANP-RIA-reactive material: the first one in the position of urodilatin, the second one coeluting with synthetic ANP and a third late eluting peak, possibly containing degradation products. The physiological significance of these findings remains to be investigated.     

中枢神经系统感染血浆及脑脊液中心钠素水平与低钠血症的关系

目的　 探讨心钠素 (ANP)在中枢神经系统 (CNS)感染及合并低钠血症中所起的作用及意义。 方法 　应用放射免疫法检测 45例中枢神经系统感染患儿血浆及脑脊液中ANP的水平 ,同时检测血清钠的含量 ,并与 12例对照组比较。 结果 　(1)急性期患儿血浆ANP均高于对照组 (P <0 0 1) ,并发症组患儿升高更明显 (P <0 0 0 1) ;急性期儿脑脊液ANP均低于对照组(P <0 0 1) ,并发症组儿降低尤其明显 (P <0 0 0 1) ;(2 )中枢神经系统感染患儿血浆ANP与血清钠水平呈负相关 (r =-0 748,P<0 0 5 ) ,脑脊液ANP水平与血清钠无显著相关 (r =0 2 17,P >0 0 5 )。 结论 　 (1)中枢神经系统感染患儿血浆及脑脊液ANP水平反映脑损伤严重程度和预后 ;(2 )ANP参与低钠血症形成过程     

Interrelationship of atrial natriuretic peptide, atrial volume, and renal function in premature infants

Infants experience dramatic changes in fluid balance during the first few days of life, which provides an opportunity to observe the interrelationships of changing atrial size, atrial natriuretic peptide (ANP) secretion, and renal function during a relatively short period. To study these relationships, we examined nine infant boys (mean birth weight 1180 gm and gestational age 30 weeks) at 20 to 28 hours of age and then at four 24-hour intervals. Measurements included plasma ANP concentration, two-dimensional echocardiographic estimations of left and right atrial volumes, Doppler determination of ductus arteriosus patency, creatinine clearance, urine flow rate, urinary sodium excretion, and cyclic guanosine monophosphate (cGMP) excretion. Plasma ANP concentration was found to decrease with age and to correlate with decreasing size of the right atrium, closure of the ductus arteriosus, urinary cGMP excretion, and sodium excretion. We speculate that elevated plasma ANP values in a preterm neonate reflect an expanded volume state. As volume contraction, reflected by decreasing atrial volume and body weight occurs, ANP levels decrease, which may diminish diuresis. These findings are compatible with a significant role for ANP in volume homeostasis of newborn infants.     

Decreased antihaemophilic globulin and leucocyte response to epinephrine in preterm infants.

Twenty-one preterm and 23 term neonates, 13 splenectomized children and one with congenital asplenia, and 20 normal children were examined for plasma antihaemophilic activity and for blood leucocyte levels before and 30 minutes after a subcutaneous injection of epinephrine 0-01 mg/kg. The basal values for antihaemophilic activity were similar for the 4 groups. The response to epinephrine was a trivial rise in antihaemophilic activity in the preterm group, while the rise in the term newborns was comparable to that of the normal children. The asplenic children all showed a trivial rise. The leucocyte response was also negligible in both the preterm neonates and asplenic groups, while in the term infants it was comparable to that seen in the normal children. These results may indicate an incapacity of the preterm newborn infant''s reticuloendothelial system and spleen to react to other challenges, such as bacterial infection.     

Decreased antihaemophilic globulin and leucocyte response to epinephrine in preterm infants

Twenty-one preterm and 23 term neonates, 13 splenectomized children and one with congenital asplenia, and 20 normal children were examined for plasma antihaemophilic activity and for blood leucocyte levels before and 30 minutes after a subcutaneous injection of epinephrine 0-01 mg/kg. The basal values for antihaemophilic activity were similar for the 4 groups. The response to epinephrine was a trivial rise in antihaemophilic activity in the preterm group, while the rise in the term newborns was comparable to that of the normal children. The asplenic children all showed a trivial rise. The leucocyte response was also negligible in both the preterm neonates and asplenic groups, while in the term infants it was comparable to that seen in the normal children. These results may indicate an incapacity of the preterm newborn infant's reticuloendothelial system and spleen to react to other challenges, such as bacterial infection.     

Circulating levels of endothelin and atrial natriuretic factor during postnatal life

We determined plasma endothelin-1-like immunoreactivity and atrial natriuretic factor concentrations in preterm and full-term newborn infants during the first month of life. Plasma endothelin-1-like immunoreactivity levels were far greater than those of maternal blood in the newborn infants. The highest plasma endothelin-1-like immunoreactivity levels were observed on the first day of life (8.7 +/- 3.7 pmol/l) and gradually decreased with age. There was no significant difference in plasma endothelin-1-like immunoreactivity levels between preterm and full-term infants. A good correlation was observed between plasma endothelin-1-like immunoreactivity levels and atrial natriuretic factor concentrations (p < 0.01). These results suggest that circulating endothelin may regulate the cardiovascular system in the newborn period.     

Effects of Intralipid infusion on hemorheology and peripheral resistance in neonates and children

Deleterious microcirculatory effects of Intralipid (IL) infusion may be caused by hemorheological or vascular effects. The aim of this investigation was to study vascular and hemorheological effects of IL in preterm and fullterm neonates and children. Ten preterm newborns, 10 fullterm neonates, and 10 children received an initial infusion of IL (0.6 g/kg) over 4 h. Calf blood flow (venous occlusion plethysmography), blood pressure (Dinamap), whole blood and plasma viscosity (capillary viscometer), red blood cell deformability (rheoscope), and erythrocyte aggregation (aggregometer) were measured before and after administration of IL. Plasma triglyceride levels showed the greatest increase in preterm infants. Whole blood viscosity decreased by about 10% in all three groups because of a similar reduction in hematocrit. Red blood cell aggregation decreased by about 20% after IL infusion. Blood pressure rose by 10%, and peripheral blood flow declined by about 10% in the three groups. Vascular hindrance, a calculation of blood pressure divided by blood flow and viscosity, was raised by about 20%, suggesting marked vasoconstriction of peripheral arteries. Vasoconstriction rather than hemorheological changes during infusion of IL may play a crucial role in the pathogenesis of circulatory alterations in parenterally-fed neonates.     

迟发性维生素K缺乏性颅内出血患儿血浆心钠素与低钠血症的关系

目的探讨迟发性维生素K缺乏性颅内出血患儿心钠素(ANP)水平变化与低钠血症的关系及其临床意义。方法应用放射免疫分析技术检测108例颅内出血患儿不同病程的血浆ANP水平,同时检测血清钠的含量,选取25例健康同龄儿作为对照。结果(1)颅内出血急性期血浆ANP水平均高于对照组(P<0·05);昏迷组患儿ANP升高更明显(P<0·01);(2)颅内出血患儿血浆ANP与血清钠水平呈负相关(γ=-0·748,P<0·05)。结论(1)迟发性维生素K缺乏性颅内出血患儿血浆ANP水平反映脑损伤严重程度;(2)ANP参与迟发性维生素K缺乏性颅内出血患儿低钠血症的形成过程。     

Effects of intralipid infusion on blood viscosity and other haemorheological parameters in neonates and children

Aim: To study acute haemorheological effects of intralipid in preterm and full-term neonates and children. Circulatory complications of intralipid infusion, such as increases in pulmonary and peripheral flow resistance, have been associated with impaired blood rheology. Methods: During total parenteral nutrition, 10 preterm infants, 10 full-term neonates and 10 children received an initial dose of intralipid as continuous infusion (0.6 g/kg) over 4 h. Additionally, blood of 10 healthy preterm infants, 10 full-term neonates and 10 adults was incubated with intralipid. Whole blood and plasma viscosity (capillary viscometer), red blood cell (RBC) deformability (rheoscope) and RBC aggregation (Myrenne aggregometer) were measured before and after intralipid infusion and before and after in vitro incubation of blood with intralipid. Results: During intralipid infusion, plasma triglyceride levels increased from 0.13 ± 0.27 to 2.16 ± 0.68 g/l in the preterm infants, from 0.14 ± 0.21 to 1.64 ± 0.54 g/l in the full-term neonates and from 0.65 ± 0.31 to 2.26 ± 0.60 g/l in the children. Whole blood viscosity decreased by about 10% after intralipid in all three groups due to similar decreases in haematocrit. RBC aggregation decreased by about 20% after intralipid infusion. Plasma proteins, plasma viscosity and RBC deformation were not affected by intralipid. In vitro incubation of blood with intralipid resulted in a marked reduction of RBC aggregation that was related to the intralipid concentration. At intralipid concentrations of 4 and 8 mg/ml, no RBC aggregation was noted in preterm and full-term neonates. In adults, RBC aggregation decreased by 50%.

Conclusions: Previously described deleterious effects of intralipid on circulation can not be explained by changes in haemorheological properties.     

Plasma Dopamine, Norepinephrine, Epinephrine and DOPAC Levels in Preterm Infants Prior to and Immediately after a Sleep Ventilation Hypercarbia Test

ABSTRACT. The postnatal maturation and the adaptational ability of the sympathoadrenal system has been investigated in preterm neonates ( n =8), and in sick preterm neonates with respiratory disorders ( n = 10). Plasma levels of dopamine (DA), norepinephrine (NE), epinephrine (E) and 3–4 dihydroxyphenylacetic acid (DOPAC) were evaluated at rest during the first month of life, and following an inhalation of a 5% carbon dioxide—21% oxygen mixture for 10 min. During the first month of life the sick preterm neonates exhibited similar NE, E, and DOPAC plasma levels but higher DA amounts than healthy infants. Plasma DA levels were inversely correlated with the transcutaneous oxygen tension ( r = -0.636) indicating that hypoxemia was able to enhance the release of DA. Immediately following the hypercarbia test, there were no significant changes of plasma catecholamine levels in the sick preterms, but there was a significant increase of E plasma levels (+140%, p < 0.05) and a moderate elevation of NE and DA amounts in the healthy preterms. It is concluded that preterm neonates who have had respiratory disorders did not exhibit an immaturity of the sympathoadrenal system at rest, but had a defect in the release of E following hypercarbia exposure, which may be secondary to an alteration in chemoreceptor function and/or reduced catecholamine stores.     

Plasma dopamine, norepinephrine, epinephrine and DOPAC levels in preterm infants prior to and immediately after a sleep ventilation hypercarbia test.

The postnatal maturation and the adaptational ability of the sympathoadrenal system has been investigated in preterm neonates (n = 8), and in sick preterm neonates with respiratory disorders (n = 10). Plasma levels of dopamine (DA), norepinephrine (NE), epinephrine (E) and 3-4 dihydroxyphenylacetic acid (DOPAC) were evaluated at rest during the first month of life, and following an inhalation of a 5% carbon dioxide-21% oxygen mixture for 10 min. During the first month of life the sick preterm neonates exhibited similar NE, E, and DOPAC plasma levels but higher DA amounts than healthy infants. Plasma DA levels were inversely correlated with the transcutaneous oxygen tension (r = -0.636) indicating that hypoxemia was able to enhance the release of DA. Immediately following the hypercarbia test, there were no significant changes of plasma catecholamine levels in the sick preterms, but there was a significant increase of E plasma levels (+140%, p less than 0.05) and a moderate elevation of NE and DA amounts in the healthy preterms. It is concluded that preterm neonates who have had respiratory disorders did not exhibit an immaturity of the sympathoadrenal system at rest, but had a defect in the release of E following hypercarbia exposure, which may be secondary to an alteration in chemoreceptor function and/or reduced catecholamine stores.     

妊娠期合并糖代谢异常对新生儿胰岛素敏感性的影响

目的探讨妊娠期合并糖代谢异常对子代新生儿期胰岛素敏感性的影响。方法选择2009年12月至2010年11月本院产科出生的新生儿,根据母亲妊娠期是否合并糖代谢异常分为糖代谢异常母亲的新生儿和糖代谢正常母亲的新生儿。所有研究对象均进行出生体格测量,并于生后 3 天内测定空腹血糖( FPG) 和空腹血清胰岛素( FINS) ,计算胰岛素敏感指数( ISI) ,采用胰岛素稳态模型( HOMA) 计算胰岛素抵抗指数( IR) ,即 HOMA-IR,其中 FINS、ISI 和 HOMA-IR 值为胰岛素敏感性的评价指标。以性别、胎龄、出生体重为协变量,分别在早产儿和足月儿中进行胰岛素敏感性的协方差分析。结果 89 例早产新生儿和 96 例足月新生儿纳入分析。糖代谢异常母亲新生儿的出生体重、出生身长和重量指数( PI) 与糖代谢正常母亲的新生儿相比,差异无统计学意义( P >0. 05) 。与糖代谢正常母亲的早产儿相比,糖代谢异常母亲的早产儿 FPG 降低、FINS 升高,差异有统计学意义[FPG( mmol/L) : ( 4. 00 ±0. 25) 比( 4. 82 ±0. 18) ,FINS( 经对数 Lg 转换) : ( 0. 69± 0. 06) 比( 0. 54 ± 0. 04) ,P < 0. 05],ISI 值降低、HOMA-IR 值升高,但差异无统计学意义[ISI( 经对数 Ln 转换) : ( -2. 89 ±0. 15) 比( -2. 78 ±0. 11) ,HOMA-IR 值( 经对数 Lg 转换) : ( -0. 10 ±0. 06)比( -0. 15 ±0. 05) ,P >0. 05]; 足月儿中糖代谢异常母亲的新生儿 FPG、FINS 和 HOMA-IR 值低,ISI 值高,但差异均无统计学意义[FPG( mmol / L) : ( 4. 68 ± 0. 23) 比( 5. 17 ± 0. 13) ,FINS( 经对数 Lg转换) : ( 0. 56 ±0. 06) 比( 0. 61 ±0. 03) ,HOMA-IR 值( 经对数 Lg 转换) : ( -0. 14 ±0. 06) 比( -0. 03± 0. 03) ,ISI( 经对数 Ln 转换) : ( - 2. 79 ± 0. 14) 比( - 3. 04 ± 0. 08) ,P > 0. 05]。结论母亲妊娠期合并糖代谢异常虽然对新生儿的出生体重没有影响,但血糖仍然呈现低水平趋势,且对早产儿胰岛素敏感性可能有一定的影响。