Plasma atrial natriuretic peptide in patients with congenital heart diseases

The plasma level of human alpha-atrial natriuretic peptide was measured in healthy children and patients, 1 month to 15 years of age, with congenital heart diseases. Significant increases were found in patients with a ventricular septal defect, tricuspid valve atresia, patent ductus arteriosus, and atrial septal defect but not in those with pulmonary valve stenosis or tetralogy of Fallot. The levels were significantly higher in children with ventricular septal defects (221 +/- 123 pg/mL) or patent ductus arteriosus (124 +/- 38 pg/mL) than in those with atrial septal defects (65 +/- 42 pg/mL) (P less than .01). The increased levels appeared to be correlated with enlargement of the left atrium (r = .85, P less than .01) but not with the right atrial size or the mean right atrial pressure. They were higher in younger than in older healthy infants, but this age difference did not affect the results. These findings indicate that human alpha-atrial natriuretic peptide is released into the circulation in response to chronic atrial expansion in patients with congenital heart disease and may have an important role in volume homeostasis.     

B型尿钠肽在先天性心脏病诊治中的应用价值

B型尿钠肽（B-type natriuretic peptide,BNP）属于尿钠肽家族,1988年Sudoh等首先从猪脑中分离,因而被命名为脑钠肽（brain natriuretic peptide）,但后来发现BNP主要由心室分泌。BNP在正常心肌中很少表达,当心室的容量负荷或压力负荷增加、室壁张力增高时,BNP爆发合成、分泌增多,参与肾脏和心血管功能的整体调节,因此,BNP可作为心功能不全的特异性标记。血浆BNP浓度在成人充血性心力衰竭的诊断、危险度分层和判断治疗反应方面已显示出一定的应用价值,但在儿童先天性心脏病（congenital heart disease,CHD）合并心功能不全中的诊断与治疗价值尚有待评价。     

Plasma B-type natriuretic peptide levels in children with heart disease

Aim: To determine plasma B‐type natriuretic peptide (BNP) levels in children with heart diseases before medical or surgical treatment for monitoring therapeutic efficacy in an observational prospective clinical trial at tertiary care centre. Methods: In 522 paediatric patients at an age of 6.4 ± 5.2 years (mean ± SD; range: 14 days–18 years) with congenital heart disease (CHD), cardiomyopathies (CMP) or pulmonary arterial hypertension (PAH), plasma BNP levels were evaluated before and under treatment. Results: Most types of heart disease are associated with increased mean plasma BNP levels before treatment, with highest values in children with CMP (BNP 6165 pg/mL in dilated CMP vs. 817 pg/mL in hypertrophic, vs. 1236 pg/mL in restrictive CMP, each p < 0.05). Children with PAH showed a significant decrease in BNP levels under medical treatment (mean BNP 981 pg/mL before vs. 26 pg/mL under treatment, p < 0.05). Children with univentricular CHD undergoing surgical staged palliation showed a significant decrease in BNP levels after bidirectional cavopulmonary anastomosis (BDCP) (BNP 109 pg/mL before vs. 70 pg/mL after BDCP, p < 0.05). Conclusion: Plasma BNP levels are elevated in children with heart disease before treatment and are a useful laboratory parameter under treatment during long‐term follow‐up.     

脑钠肽和氨基末端脑钠肽在小儿先天性心脏病心功能评估中的价值

目的：探讨脑钠肽（BNP）和氨基末端脑钠肽（NT-proBNP）在小儿先天性心脏病心功能评估中的价值。方法：71例先天性心脏病患儿分为无心力衰竭组和心衰组;35例正常儿童作为对照组。应用微粒子酶免疫分析法和电化学发光法分别测定血浆BNP和NT-proBNP浓度。同时测定左室舒张末期内径指数（LVEDDI）、左室射血分数（LVEF）。结果：心衰组血浆BNP和NT-proBNP水平明显高于无心衰组(均P<0.01);无心衰组血浆BNP和NT-proBNP水平明显高于对照组(均P<0.01) 。心衰组血浆LogBNP和LogNT-proBNP水平与LVEF均呈负相关(r=-0.64,-0.67,均P<0.01);二者水平与LVEDDI均呈正相关（r=0.58,0.76,均P<0.01）。无心衰组血浆LogBNP和LogNT-proBNP水平与LVEF均无明显相关性;血浆LogNT-proBNP水平与LVEDDI呈正相关（r=0.35,P<0.05）。分别以BNP≥149.8 pg/mL,NT-proBNP≥820.1 pg/mL作为充血性心力衰竭的诊断阈值,二者的敏感度分别为87.0％,91.3％,特异度分别为91.7％,97.9％,ROC曲线下面积分别为0.935,0.987。结论：BNP和NT-proBNP均可用于先天性心脏病患儿心功能的评估,并可用于该类患儿充血性心力衰竭的诊断;与BNP比较,NT-proBNP诊断心衰的价值更高。［中国当代儿科杂志,2009,11（6）：429-432］     

NT-proBNP达峰时间对儿童先天性心脏病术后早期预后的预测价值

目的 探讨血清氨基末端脑钠肽前体(N-terminal pro-brain natriuretic peptide,NT-proBNP)的变化,对先天性心脏病患儿术后早期预后的预测价值.方法 选择2014年6-12月在全身麻醉、体外循环下行先天性心脏病手术415例患儿,在术前及术后早期(1、12、36、60 h和1周)测定NT-proBNP,并收集一般临床资料.各时间点NT-proBNP的比较采用配对t检验及重复测量数据的方差分析,使用ROC曲线评价NT-proBNP预测机械通气时间＞48 h、术后ICU停留时间＞3 d、血管活性药物使用时间＞3 d的诊断效能,总体诊断效能用ROC曲线下面积(AUC)及95％可信区间表示.结果 全组平均NT-proBNP达峰时间为术后12h.其中296例NT-proBNP在术后12h内达到峰值(12h内达峰组),其余119例均在12h后达到峰值(12 h后达峰组).12h内达峰组术后机械通气时间为(29.19±33.34)h,12h后达峰组为(49.16±85.85)h,组间比较,差异有统计学意义(t=2.465,P=0.015).12h内达峰组ICU停留时间为(3.69±2.73)d,12 h后达峰组为(5.57±5.64)d,组间比较,差异有统计学意义(t=3.479,P=0.001).12h内达峰组血管活性药物使用时间＞3 d比例为35.8％(106/296),12 h后达峰组为52.9％(63/119),组间比较,差异有统计学意义(x2=10.318,P=0.002).通过ROC曲线计算术后12 h NT-proBNP预测机械通气时间＞48 h的曲线下面积(AUC)为80.1％(95％可信区间75.0％～85.1％),最佳界值为7 708.71 pg/ml,灵敏度为65.1％,特异度为81.8％.术后12 h NT-proBNP预测血管活性药物使用时间＞3 d的AUC为78.4％(95％可信区间为73.9％～82.9％),最佳界值为6 145.67 pg/ml,灵敏度为82.5％,特异度为62.7％.术后12hNT-proBNP预测术后ICU停留时间＞3 d的AUC为77.5％(95％可信区间为73.0％～82.1％),最佳界值为4 981.77 pg/ml,灵敏度为68.7％,特异度为76.4％.结论 血清NT-proBNP是小儿先天性心脏病术后估测早期预后的一个敏感指标,在协助判断先天性心脏病术后患儿机械通气时间、血管活性药物使用时间、ICU停留时间方面有一定的临床应用价值.     

Plasma atrial natriuretic peptide and spontaneous diuresis in sick neonates.

Plasma concentrations of immunoreactive human atrial natriuretic peptide (human ANP) were sequentially determined in 12 infants with respiratory distress syndrome (RDS) or meconium aspiration syndrome (MAS) during various phases of diuresis to elucidate the role of human ANP in the occurrence of spontaneous diuresis in the newborn. Plasma immunoreactive ANP concentrations during the diuretic as well as the maximum diuretic phase were significantly (p less than 0.001) higher than during the prediuretic phase. A gradual decrease occurred during the post diuretic phase, returning to prediuretic values after one week of life. Significant natriuresis, increased glomerular filtration rate, mild hyponatremia, and decreased blood pressure were observed in the diuretic phase in all the cases studied. These results suggest that hypersecretion of human ANP may play an important part in initiating spontaneous diuresis in sick neonates.     

Plasma brain natriuretic peptide concentrations in patients with Kawasaki disease

BACKGROUND: Brain natriuretic peptide (BNP) is a cardiac hormone and plasma levels of it increase in patients with congestive heart failure and in those with acute myocardial infarction. Kawasaki disease (KD) is a well-known generalized vasculitis and the most prominent features of this disease are the cardiovascular manifestations, which involve the pericardium, myocardium, endocardium and coronary arteries. It was hypothesized that the plasma concentrations of BNP in patients with KD might be increased and that plasma BNP might be a useful biological marker of cardiovascular manifestations in patients with KD. METHODS: Blood was obtained to measure and compare plasma BNP concentrations in the acute (n = 32) and convalescent (n = 35) phases of KD and in the acute phase of the patients with viral infection (n = 26), which included adenovirus, influenza, measles and herpes group virus infection. In patients with KD, two-dimensional echocardiography was performed to check for pericardial effusion and coronary arterial lesions and to measure the dimensions of the left ventricle at diastole and the shortening fraction of the left ventricle (LVSF). RESULTS: The mean plasma BNP concentration in patients with KD in the acute phase was 55.0 +/- 39.5 pg/mL, but was 6.8 +/- 7.3 pg/mL in patients with viral infection. The plasma BNP concentration in patients with KD in the acute phase was significantly higher than in patients with viral infection (P < 0.0001). In 31 cases of KD, the plasma BNP concentrations were measured both in the acute and convalescent phases. The mean plasma BNP concentration in the acute phase of KD was 55.3 +/- 40.1 pg/mL and in the convalescent phase was 5.9 +/- 5.7 pg/mL. The level of plasma BNP decreased significantly in the convalescent phase (P < 0.0001). The mean BNP level in patients with KD with pericardial effusion (n = 8) in the acute phase was 80.3 +/- 43.4 pg/mL and that in patients without pericardial effusion (n = 24) was 46.5 +/- 35.1 pg/mL. The BNP level in patients with pericardial effusion was significantly higher than that of patients without pericardial effusion (P < 0.05). There was no significant correlation between the plasma concentrations of BNP in the acute phase of KD and LVSF (r = -0.161, P = 0.39, n = 31). CONCLUSION: It was shown that the plasma BNP concentration increased in the acute phase of KD and decreased to within normal range in the convalescent phase. Further examinations are needed to clarify the mechanism by which the elevated levels of plasma BNP occur in the acute phase of KD. However, plasma BNP might be a useful biological marker of the cardiovascular manifestations in patients with KD.     

婴幼儿先天性心脏病术前氨基末端B型脑利钠肽前体检测的临床意义

目的 检测婴幼儿先天性心脏病（CHD）术前血浆氨基末端B型脑利钠肽前体（NT-proBNP）,探寻CHD患儿术前合并充血性心力衰竭（CHF）血浆NT-proBNP诊断界值,对术前心功能维护的效果进行评价。方法 测定2010年6月至2013年6月收治的120例术前婴幼儿CHD患儿及100例正常儿童（对照组）血浆NT-proBNP水平,将合并CHF的CHD患儿（CHF组）又分为婴儿组（<1岁）和幼儿组（≥1岁）,探寻NT-proBNP在不同年龄段CHF患儿中诊断CHF的界值。结果 120例婴幼儿CHD中41例符合改良Ross心力衰竭诊断标准,CHF组NT-proBNP诊断CHF界值为≥498 ng/L,婴儿组和幼儿组的NT-proBNP诊断CHF界值分别为557 ng/L、452 ng/L。41例CHF患儿经治疗后NT-proBNP较治疗前明显下降,其差异有统计学意义（P<0.001）。结论 婴儿组与幼儿组的NT-proBNP诊断CHF的界值存在明显差异。血浆NT-proBNP可作为CHD婴幼儿术前心功能评估的一个指标。     

Increased serum high-sensitivity C-reactive protein is related to hypoxia and brain natriuretic peptide in congenital heart disease

Background: Studies of adults have shown a direct association between increased serum concentrations of high-sensitivity C-reactive protein (hs-CRP) and atherosclerotic cardiovascular disease, diabetes, and chronic heart failure. Some studies have documented elevated hs-CRP in obese children and adolescents, and in patients with a history of Kawasaki disease, but there are few data on its clinical significance in congenital heart disease.
Methods: Measurements of hs-CRP, brain natriuretic peptide (BNP), hemoglobin, and percutaneous oxygen saturation (SpO2) were done in the following 70 patients: 18 controls; 11 with hypoxia (SpO2 ≤ 85% and BNP < 40 pg/mL); 31 with raised BNP (BNP ≥ 40 pg/mL and SpO2 > 85%); and 10 patients with hypoxia–BNP (SpO2 ≤ 85% and BNP ≥ 40 pg/mL). Correlations between hs-CRP, and age, body mass index (BMI), hemoglobin, SpO2, and BNP were analyzed using single and multiple regression analysis.
Results: Hs-CRP in the hypoxia–BNP group was higher than in the other three groups, while in the hypoxia and the BNP groups it tended to be higher than in the controls. Although single regression analysis showed significant correlations between hs-CRP and, age, BNP, hemoglobin, and SpO2, multiple regression analysis showed that only BNP and SpO2 had a significant correlation with hs-CRP.
Conclusions: In preoperative or postoperative congenital heart disease, patients who had hypoxia or increased BNP had a higher hs-CRP level than controls. Serum concentration of hs-CRP significantly correlated with SpO2 and plasma BNP levels, but not with age or BMI.     

现有儿科心力衰竭诊断标准及脑利钠肽对先天性心脏病合并心力衰竭的诊断价值

目的 拟评估现有儿科心力衰竭（简称心衰）诊断标准及血浆脑利钠肽（BNP）、无生物活性的氨基末端BNP（NT—proBNP）对先天性心脏病（简称先心病）合并心衰的诊断价值,并通过多因素分析探讨最有价值的诊断指标。方法以先心病患儿118例为研究对象,分别应用改良Ross标准、青岛标准、NYUPHFI、Ross标准以及血浆BNP、NT—proBNP对上述病例进行诊断。以改良Ross评分≥3分作为参考标准,评估各标准及血浆BNP、NT—proBNP的诊断价值。应用logistic回归方法分析各因素对心衰的诊断价值。结果 （1）各临床标准诊断心衰的价值：①青岛标准诊断的敏感度为47．9％,特异度为100％,准确率为57、6％。②Ross评分诊断心衰的ROC曲线下面积为0．985,敏感度为88％,特异度为100％。③NYuPHFI评分＞2分作为诊断界点时敏感度高而特异度较低,敏感度为100％,特异度为4．5％。（2）血浆BNP及NT—proBNP与改良Ross呈正相关,随着心功能分级严重程度的增加而增加,BNP诊断心衰的ROC曲线下面积为0．880,按照ROC曲线选取的诊断界值为≥349pg／ml。NT—proBNP诊断心衰的ROC曲线下面积为0.981,按照ROC曲线选取的诊断界值为≥499fmol／ml。（3）多因素分析提示,NT—proBNP、呼吸急促、心率增快、呼吸增快、生长发育落后对于心衰的诊断有价值。（4）血浆NT—proBNP与临床标准并联或串联可提高准确率。结论 现有临床标准对于先心病合并心衰均具有诊断价值,但青岛标准敏感度低,Ross标准适用范围窄,NYU PHFI＞2分特异度低,存在一定的局限性。血浆BNP及NT—proBNP对于小儿先心病导致的心衰具有诊断价值,NT—proBNP是心衰诊断的独立预测因素。     

Plasma renin activity in infants with congenital heart disease.

Plasma renin activity was estimated in 11 infants with severe congestive heart failure. The infants had congenital heart disease with left to right shunts and were receiving diuretic treatment. Plasma renin activity was measured by radioimmunoassay of generated concentrations of angiotensin I. The mean (SD) plasma renin activity was 84 (21) ng angiotensin I/ml/hour, which is considerably above normal infant values. A hyperactive renin-angiotensin system may be detrimental in these patients. Angiotensin converting enzyme inhibitors may be of value in treating infants with severe congestive heart failure.     

肾上腺髓质素在先天性心脏病中的测定及临床意义

目的：肾上腺髓质素(ADM)对心血管疾病有多方面的影响,但其与先天性心脏病关系的研究较少。该实验通过检测不同类型先天性心脏病患儿体内ADM的变化,分析ADM在先天性心脏病病理生理中的作用。方法：筛选住院的48例先天性心脏病患儿,经超声心动图及心导管检查术证实,在心导管检查术中测定血流动力学指数及采血备测,依据血流动力学特征分为高肺血流非肺动脉高压组、高肺血流并肺动脉高压组、紫绀组,平均肺动脉压(mPAP)>20 mmHg为肺动脉高压的标准。选6例川崎病痊愈患儿作为对照组。采用特异性放射免疫法检测血浆ADM的水平。结果：先天性心脏病患儿股静脉中的血浆ADM水平较股动脉明显增高(P<0.05);与对照组相比,高肺血流并肺高压组及紫绀组中的ADM明显增高,均P<0.01;ADM与主动脉平均压(mSAP)、混合静脉血氧饱和度(MVsat)、主动脉血氧饱和度(AOsat)及肺血管阻力(Rp)之间有密切的关系。结论：高肺血流并肺动脉高压和紫绀型先天性心脏病患儿的ADM水平增高,ADM的变化同肺动脉阻力和缺氧有密切关系,推测ADM水平的升高可能有助于减轻肺动脉阻力和改善缺氧。     

Cerebrospinal fluid concentrations of atrial natriuretic peptide in children

Concentrations of atrial natriuretic peptide (ANP) in plasma and in cerebrospinal fluid (CSF) were measured in preterm neonates, in infants and in children with hydrocephalus. Plasma ANP in preterm neonates were elevated compared to infants and children with hydrocephalus. CSF-ANP in all groups were lower than plasma levels. ANP concentrations in the liquor exhibited higher values in children with hydrocephalus. No correlation was found between plasma and CSF-ANP levels while CSF-pressure and ANP concentration in the liquor correlated positively. Our data provide evidence for the existence of a cerebral ANP system in humans. The CSF-ANP system seems to be independent from the systemic, atrial ANP. CSF-ANP may be of great importance in the regulation of water and ion content of central nervous system and probably liquor formation.     

Cardiac atrial natriuretic peptide in monocrotaline-induced pulmonary hypertensive rats

To determine the time course and potential triggers for synthesis of atrial natriuretic peptide (ANP) in right ventricle during the development of right ventricular hypertrophy (RVH), we measured mean right atrial pressure, right ventricular systolic pressure (RVSP), immunoreactive ANP (iANP) concentrations in plasma, and cardiac iANP concentrations and contents of monocrotaline (MCT)-induced pulmonary hypertensive rats treated with a subcutaneous injection of MCT (40 mg/kg). Following the development of RVH and pulmonary hypertension, iANP concentrations in plasma and iANP concentrations and contents in ventricular tissues increased with time. At the third week after treatment, iANP concentrations in MCT rats increased 6-fold in plasma, 57-fold in the right ventricular free wall, 20-fold in the ventricular septum and 10-fold in the left ventricular free wall compared with those in controls. At the third week, iANP contents of total ventricular tissues in MCT and control rats were 29% and 0.8%, respectively, of the corresponding atrial contents. The iANP concentrations and contents of right ventricular free walls in MCT rats were greater than those of any other parts of ventricular tissues. The iANP concentrations in right ventricular free walls were very closely related to RVSP (r = 0.93, P < 0.001). In MCT rats, iANP concentrations in right atrial tissues decreased with time. This study shows that ventricular ANP contributes to the amount of ANP stored within the heart in MCT rats and that pressure overload may be one of the triggers for ANP synthesis in the right ventricle.