Iron deficiency and cyanotic breath-holding spells: The effectiveness of iron therapy

Abstract

Aim: Frequent cyanotic breath holding spells cause fear and severe anxiety to parents. This study aimed to evaluate clinical, laboratory and treatment characteristics of children with cyanotic breath holding spells. Methods: Included were 180 children (mean age: 1.82?±?0.53 years) with cyanotic breath holding spells. They were divided into three groups: with iron deficiency, with iron deficiency anemia and without iron deficiency. Blood hemoglobin (HB), ferritin and iron concentrations were measured at baseline and after 3 and 6 months of iron treatment. Results: The mean spell frequency was 24.57?±?7.31/months, 83% had spells after the age of 1 year, 37% had daily spells, 16% had family history of spells, and 61% had Iron deficiency/Iron deficiency anemia (p?=?.001). No significant difference in the frequency of spells between children with iron deficiency and those with Iron deficiency anemia. Compared to patients without iron deficiency, there was significant reduction of spells frequency, increased hemoglobin, ferritin and iron levels after 3 and 6 months of iron therapy (p?=?.0001). Negative correlations were observed between spell frequency with hemoglobin (p?=?.001), ferritin (p?=?.0001) and iron (p?=?.001) levels. Conclusion: Not only Iron deficiency anemia but also iron deficiency alone without anemia is associated with a risk of high-frequency cyanotic breath holding spells. Iron therapy results in reduction in spells’ frequency which was correlated with increasing ferritin and iron levels.     

The contribution of pulse oximetry to the early detection of congenital heart disease in newborns

Approximately half of all newborns with congenital heart disease are asymptomatic in the first few days of life. Early detection of ductal-dependant cardiac malformations prior to ductal closure is, however, of significant clinical importance, as the treatment outcome is related to the time of diagnosis. Pulse oximetry has been proposed for early detection of congenital heart disease. The aims of the present study were: 1) to determine the effectiveness of a pulse-oximetric screening performed on the first day of life for the detection of congenital heart disease in otherwise healthy newborns and 2) to determine if a pulse-oximetric screening combined with clinical examination is superior in the diagnosis of congenital heart disease to clinical examination alone. This is a prospective, multi-centre study. Postductal pulse oximetry was performed between six and twelve hours of age in all newborns of greater than 35 weeks gestation. If pulse-oximetry-measured arterial oxygen saturation was less than 95%, echocardiography was performed. Pulse oximetry was performed in 3,262 newborns. Twenty-four infants (0.7%) had repeated saturations of less than 95%. Of these infants, 17 had congenital heart disease and five of the remaining seven had persistent pulmonary hypertension. No infant with a ductal-dependant or cyanotic congenital heart disease exhibited saturation values greater or equal to 95%. Conclusion: postductal pulse-oximetric screening in the first few days of life is an effective means for detecting cyanotic congenital heart disease in otherwise healthy newborns.     

Impairment of urate excretion in patients with cardiac disease

The serum uric acid levels and uric acid clearance rates were evaluated in 28 patients who had congenital heart disease. Based on hemodynamic assessments, the patients were divided into three groups: group 1, with normal cardiac output and normal arterial oxygen saturation; group 2, with hypoxemia (normal cardiac output with a decreased arterial oxygen saturation); and group 3, with cardiomyopathy (decreased cardiac output). The blood levels of uric acid were elevated in group 3. The mean serum uric acid levels were as follows: group 1, 4.2 mg/dL; group 2, 4.8 mg/dL; and group 3, 11.7 mg/dL. All the patients in groups 2 and 3 had decreased uric acid clearance rates. The mean uric acid clearance rates were as follows: group 1, 10.1 mL/min/sq m; group 2, 4.2 mL/min/sq m; and group 3, 1.7 mL/min/sq m. The patients in group 3 had the most severe abnormalities. Patients with congenital heart disease may have marked impairment of their uric acid excretion, which can occur in the absence of significant renal disease, and may be found in acyanotic as well as cyanotic patients.     

Auditory brainstem responses in children with congenital heart disease

BACKGROUND: Cyanotic congenital heart diseases usually lead to growth and developmental delay in children due to chronic hypoxemia and undernourishment that may affect the central nervous system. The auditory brainstem responses are determined to assess the maturation and function of the brainstem. Therefore, we used the auditory brainstem responses to investigate the effect of cyanotic congenital heart diseases on brainstem maturation. METHODS: The auditory brainstem responses were investigated in 45 children (23 cyanotic, 22 acyanotic) with congenital heart diseases and compared with the results of 30 healthy counterparts (all children were aged between 2 months and 15 years). RESULTS: The results of auditory brainstem responses were similar in acyanotic patients and in normal children. The cyanotic patients under 1 year of age had more prolonged I-V interpeak latencies than those of control and acyanotic patients (P < 0.05). There was no difference between all groups older than 1 year of age. In cyanotic children, I-V interpeak latencies showed significant negative correlation with arterial oxygen saturation and partial oxygen pressure (P < 0.05). CONCLUSIONS: Cyanotic congenital heart diseases may cause significant retardation on brainstem maturation due to chronic hypoxemia, especially in infants under 1 year of age, whereas acyanotic congenital heart diseases have no effect on auditory brainstem responses.     

Effects of oxygen and nitric oxide in oxygen on pulmonary arterial pressures of children with congenital cardiac defects

Inhaled nitric oxide is a specific pulmonary vasodilator. This study was undertaken to assess the effect on pulmonary arterial pressure of administering 100% oxygen compared with nitric oxide in oxygen. Thirteen mechanically ventilated children undergoing routine cardiac catheterization for the investigation of congenital heart disease were studied. Pulmonary arterial pressures were measured during inhalation of 30% oxygen (baseline), 100% oxygen, and nitric oxide (40 parts per million) in oxygen. In addition, in six children the pulmonary/systemic blood flow ratio and pulmonary vascular resistance were calculated using oxygen content, an assumed value for oxygen uptake, and the Fick principle. Results were compared using analysis of variance and the Wilcoxon signed-rank test. Pulmonary arterial pressure decreased from a mean value of 29.5 mmHg (SD 15.1) to 25.6 mmHg (SD 9.3), p= 0.048, after increasing the inspired oxygen fraction from 0.3 to 1.0. The addition of nitric oxide caused a further reduction to 22.9 mmHg (SD 7.9), p= 0.0001. There was no change in systemic arterial pressure or heart rate during the study period, but a small increase occurred in the mean methemoglobin level (1.1% to 1.3%) p= 0.039. Changes in the pulmonary/systemic blood flow ratio and pulmonary vascular resistance (n= 6) were not significant. Nitric oxide in oxygen appears to be a more potent pulmonary vasodilator than oxygen alone in pediatric patients with congenital cardiac defects.     

Arterial oxygen tension and response to oxygen breathing in differential diagnosis of congenital heart disease in infancy.

Arterial oxygen tension was measured from radial artery samples in 276 infants referred for cardiological investigation. Values obtained during air breathing in infants with congenital heart disease showed considerable overlap between ''cyanotic'' and ''acyanotic'' groups, and are of limited diagnostic use. By contrast, values obtained while breathing oxygen in concentrations of over 80%, measured in 182 infants, allowed clear differentiation between these groups. All infants with acyanotic, but only 2 of 109 with cyanotic lesions, achieved an arterial oxygen tension of more than 150 mmHg. In the cyanotic group the response to oxygen breathing was significantly greater in common mixing situations and in the hypoplastic left heart syndrome than with either pulmonary outflow tract obstruction or transposition of the great arteries. Infants with transposition had a significantly lower mean arterial oxygen tension in air than infants with other forms of cyanotic congenital heart disease. Of 23 infants whose final diagnosis was primary lung disease but in whom cyanotic congenital heart disease had been suspected, 7 achieved arterial oxygen tensions of more than 150 mmHg during oxygen breathing, and on this basis cardiac catheterization was not performed. We therefore conclude that measurement of the arterial oxygen tension while breathing high concentrations of oxygen should be routinely performed in the initial assessment of sick infants with suspected congenital heart disease.     

Correlation of Plasma Adrenomedullin to Myocardial Preservation During Open-Heart Surgery

Adrenomedullin (ADM) is a vasoactive peptide with potent dilatory effects. We studied whether perioperative myocardial injury could be altered by the presence of ADM. Blood samples from 19 children with congenital heart disease undergoing surgical repair were collected at six time points: preoperative, on cardiopulmonary bypass (CPB), and 0, 3, 6, and 12 hours after CPB. Blood levels of ADM (pg/ml) and troponin-I (Tn-I; ng/ml), a specific marker of myocardial injury, were measured. Patients were divided into three groups based on their 12-hour Tn-I levels (I, < 10, n= 6; II, 10–25, n= 6; III, >25, n= 7). Preoperative Tn-I levels were within the normal range for all patients. Preoperative ADM levels in group I (with little or no evidence of myocardial injury) were significantly greater than those of either group II or III (242.7 ± 15.4 vs 83.8 ± 18 and 85.2 ± 5.5, respectively; p≤ 0.0001 for each). The 12-hour ADM levels in group I remained significantly lower than preoperative levels (242.7 ± 15.4 vs 197.4 ± 11.6, p≤ 0.03) but higher than in the other groups. In group III, ADM increased at the 12-hour time point (159.2 ± 6.5, p≤ 0.0001 vs baseline). Higher preoperative ADM levels are associated with lower levels of myocardial injury (as assessed by troponin-I release) during congenital heart surgery.     

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.     

Repolarization Patterns in Congenital Heart Disease

The aim of this study was to study the repolarization patterns in pediatric patients with cyanotic and acyanotic congenital heart diseases as prolonged QT indicates a myocardium at risk of ventricular arrhythmia. A cross-sectional case–control study included 50 patients with acyanotic congenital heart diseases and 50 patients with cyanotic congenital heart diseases who presented to Catheterization Unit of Cairo University Pediatric Hospital between March 2013 and June 2014. We included 50 healthy children as a control. For all the patients’ measurement of oxygen saturation, echocardiography and 12-lead electrocardiogram (ECG) were done and the corrected QT (QTc) was measured. The mean QTc was significantly higher in acyanotic congenital heart diseases with volume overload than in control: 0.426 versus 0.4 s (p = 0.009). Increased left ventricular end-diastolic dimension was significantly associated with QTc prolongation (p = 0.01). Early repolarization was higher in congenital heart diseases (18 % in acyanotic patient, 48 % in cyanotic patients) than in control 6 %. Decreased oxygen saturation was significantly associated with early repolarization (p = 0.01). Prolonged QTc was higher in acyanotic congenital heart diseases with volume overload and increased left ventricular end diastolic dimension was a significant association. Decreased oxygen saturation was a significant association.     

Redistribution of regional blood flow and oxygen delivery in experimental cyanotic heart disease in newborn lambs

Redistribution of regional blood flow is an important compensatory response to acute hypoxemia which preserves oxygen delivery to the most vital organs. It is not known if this change in blood flow persists when hypoxemia is prolonged, as occurs in cyanotic congenital heart disease. Chronic hypoxemia was produced in newborn lambs by creating pulmonary stenosis and an atrial septal defect. Oxygen saturation was maintained at 60-70% of control for 2 wk. Distribution of cardiac output was then measured with radionuclide-labeled microspheres. As compared with control, chronic hypoxemia did not alter total cardiac output. Regional blood flow was redistributed, however, the pattern of this redistribution was different from that seen during acute hypoxemia. Myocardial and cerebral blood flows, which increase during acute hypoxemia, return to control levels during chronic hypoxemia. Renal, splenic, gastrointestinal, carcass, and skin blood flows remain decreased. Hemoglobin gradually increases so that after 2 wk of hypoxemia total systemic oxygen delivery returns toward control. However, oxygen delivery to all organs except the heart and brain is reduced. Thus, although cardiac output and total systemic oxygen delivery return toward normal during chronic hypoxemia, these measurements may not reflect important regional variations in blood flow and oxygen delivery. Decreased oxygen and substrate delivery to the gastrointestinal tract, liver, and carcass may account for the alterations of metabolism and growth seen in the newborn with cyanotic congenital heart disease.     

Myocardial perfusion in children with sickle cell anaemia

Background. Myocardial ischaemia is an unexpected complication with potentially serious clinical damages in patients with sickle cell anaemia (SCA). Conventional techniques, such as exercise testing and echocardiography, have low sensitivity and specificity for the detection of myocardial ischaemia in patients with SCA. Objective. To assess myocardial perfusion using thallium-201 (²⁰¹Tl) single-photon emission computed tomography (SPECT) in children with SCA. Materials and methods. Eight patients (11.5 ± 5.0 years, mean ± SD) who were free of cardiac symptoms were studied. Myocardial perfusion was assessed by ²⁰¹Tl-SPECT after stress and 3 h later after a further injection. Left ventricular ejection fraction (LVEF) was assessed by equilibrium radionuclide angiography. Results. Myocardial perfusion was abnormal in three of eight patients: two had reversible defects and one had a fixed defect. The mean LVEF was 53 ± 8 %. There was no relationship between myocardial perfusion and LVEF. Conclusions. Treatment of asymptomatic myocardial ischaemia remains unclear, and more aggressive therapy of the haematological disease should be considered. Received: 17 October 1999 Accepted: 15 November 1999     

Prehospital Discharge Car Safety Seat Testing of Infants After Congenital Heart Surgery

Background This study aimed to expand the American Academy of Pediatrics (AAP) car safety seat testing recommendation to include high-risk infants after cardiac surgery. Methods Car safety seat testing (≤4 days before discharge), performed according to AAP guidelines, was retrospectively reviewed for 66 postoperative infants. Failure was defined as apnea, bradycardia, or oxygen desaturation. Results The average birth weight of the study infants was 3.1 ± 0.5 kg. Two patients were born at less than 37 weeks gestation. Surgical procedures included modified Blalock–Taussig shunt technique (n = 15), arterial switch operation (n = 12), Norwood Sano modification (n = 11), coarctation repair (n = 8), repair of tetralogy of Fallot (n = 6), repair of truncus arteriosus (n = 4), repair of total anomalous pulmonary venous return (n = 3), pacemaker placement (n = 2), repair of interrupted aortic arch and ventriculoseptal defect (VSD) (n = 1), repair of coarctation and VSD (n = 1), orthotopic heart transplant (n = 1), repair of VSD (n = 1), and patent ductus arteriosus ligation (n = 1). The average age at discharge was 28 ± 21 days. Four patients (6%) failed car safety seat testing because of a fall in oxygen saturation. One of the four patients passed on retesting after parental education, whereas three of the four (75%) were discharged home in a supine car safety seat. There was no relationship between the type of surgery and car safety seat test failure. Conclusion It may be beneficial to extend the AAP recommendations for car safety seat testing to include high-risk infants after cardiac surgery.     

Is Oxygen Supply the Only Regulator of Erythropoietin Levels?Serum Immunoreactive Erythropoietin during the First 4 Months of Life in Term Infants with Different Levels of Arterial Oxygenation

ABSTRACT. Serum immunoreactive erythropoietin (siEp) levels were measured in 35 full-term infants aged 0–13 weeks, 31 of whom had congenital heart disease. The infants displayed a wide range in arterial oxygen tension (Pa_o2) and oxygen saturation (Sa_o2). During the first days of life siEp varied widely with a range from less than 3 to more than 10000 mIU/ml. The wide variation is consistent with findings in cord blood at term. The siEp levels did not correlate significantly with haemoglobin, haematocrit, Pa_o2, Sa_o2, or arterial oxygen content in the total sample, nor when the cohort was split up into different age groups. Cyanotic infants aged 2–13 weeks had significantly higher siEp concentrations than normal adults ( p <0.001) and than children with cyanotic congenital heart disease, aged 4 months-10 years ( p <0.001). The raised siEp levels in cyanotic children aged 2–13 weeks found in this study and the normal levels found in their older counterparts (4 months-10 years) (reported elsewhere) are consistent with the pattern observed in man and animals exposed to prolonged hypobaric hypoxia, in which after an initial rise in erythropoietin concentrations the levels fall to normal while increased erythropoiesis is sustained.     

Platelet activation in congenital heart diseases

The research presented here investigated platelet activation in cyanotic and acyanotic congenital heart diseases (CHD). Children with cyanotic CHD are prone to both thrombosis and hemorrhage. However, patients with acyanotic CHD may also have a mild bleeding disorder. The platelet activation in CHD was investigated in support of a hypothesis that platelet activation may play a role in the hemostatic abnormalities reported in these patients. Platelet activation was determined by using flow cytometry with anti-CD62 monoclonal antibody (mAb), which has been shown to be a specific marker of platelet activation. Thirteen children with cyanotic CHD, 33 children with acyanotic CHD and 17 healthy children serving as controls were studied. Platelet activation was significantly higher in the cyanotic group and also in the acyanotic group compared with the healthy children (P = 0.0000 and P = 0.019, respectively). In the cyanotic group, platelet activation showed a direct correlation with arterial O₂ saturation (SaO₂) (P = 0.014). There was no correlation between platelet activation and erythrocyte related parameters in either group. Platelet activation occurs in CHD, particularly in patients with cyanotic CHD (even in patients with no evidence of clinical thrombosis) and it may play a role in the pathogenesis of thrombotic disorders seen in these patients.     

Prostaglandin E1 therapy in infants with cyanotic congenital heart malformations: hemodynamic and angiographic findings (author's transl)

During emergency cardiac catheterization, the mechanism of action of prostaglandin E1 (PG-E1) was studied in 7 newborn infants with cyanotic congenital heart malformations and decreased pulmonary blood flow. The main effects upon hemodynamics were an increase of pulmonary blood flow and a decrease of systemic blood flow. At the same time systemic blood pressure decreased slightly and a rise in systemic vascular resistance was calculated. An aortogram before and 15--20 minutes after the infusion of Pg-E1 was started, demonstrated a marked increase of the pulmonary blood flow and a dilation of the ductus arteriosus. Together with these hemodynamic effects the arterial and central venous oxygen saturation rose. In one infant with severe Tetralogy of Fallot, the ductus had already closed and could not be reopened by PgE1. In this infant PG-E1-Infusion had no effect upon arterial oxygen saturation. From these observations it can be concluded that dilation of the ductus is responsible for the rise in arterial oxygen saturation. 3the different indications for therapy with PG-E1 in the neonate are discussed.     

Nebulized hypertonic saline and recombinant human DNase in the treatment of pulmonary atelectasis in newborns

Objective: The aim of this study was to compare and evaluate the efficacy of nebulized 3% hypertonic saline (HS) and recombinant human DNase (rhDNase) treatment for resolution of persistent atelectasis in newborns. Study design: Forty newborns (38 preterms) who did not respond to conventional treatment were enrolled to receive either nebulized 3% HS solution (n = 20) or rhDNase (n = 20) between September 2007 and March 2008. Clinical parameters, oxygen saturation and radiological response (chest X‐ray scoring) were analyzed before and after administration of 3% HS or rhDNase. Results: The patients of the nebulized 3% HS solution group improved better chest X‐ray scores parameters than the patients of the rhDNase group: chest X‐ray scores were 5.1 ± 1.9 vs 4.8 ± 1.7 before treatment and 1.0 ± 0.8 vs 2.1 ± 1.4 after treatment (P < 0.001). Resolution time of atelectasis did not differ between the two groups after whole treatment but the percentage of atelectasis resolution after 3 days treatment were 90% (18/20) in the 3% HS group and 70% (14/20) in the rhDNase group. The patients in the 3% HS group improved better also in clinical parameters in comparison to the rhDNase treatment. The difference of oxygen saturation before and after the treatment was 4.6 ± 0.8 in 3% HS group in comparison to 2.6 ± 0.1 in the rhDNase group (P < 0.05). All serum sodium levels were normal in two groups before and after the treatment modalities. Conclusion: This is the first study on the usefulness of nebulized 3% hypertonic saline solution in treating newborns with pulmonary atelectasis. In addition, 3% HS solution was a more effective therapeutic option on the basis of clinical and radiological improvement compared to rhDNase treatment in newborns with pulmonary atelectasis.     

Delayed recognition of haemodynamically relevant congenital heart disease

Delayed recognition of congenital heart defects may have a serious impact on the long-term outcome of the children affected. It was the aim of the present study, to evaluate the proportion of children with delayed cardiac diagnosis out of a large cohort of consecutive paediatric patients requiring treatment for congenital heart disease. A prospective study was performed over a 3-year period. Of all 323 paediatric patients requiring surgical (n=291) or catheter interventional (n=32) treatment for congenital heart disease, patients with delayed diagnosis of their cardiac defects were observed and especially examined for the presence of clinical cardiac findings other than systolic murmurs, not recognized as such prior to referral. Of all the patients, 32 (10%) had delayed diagnosis of heart defects. Surprisingly, the proportion of late diagnoses was not different in the group of patients with cyanotic heart disease where 7/72 patients were referrred with delay, compared to 25 delayed referrals among 251 children with acyanotic heart defects. Of the 32 patients with delayed diagnosis, 7 had complications due to delayed referral, but there was no mortality associated with late diagnosis. Conclusion A substantial proportion of all paediatric patients requiring intervention for heart disease were diagnosed with relevant delay. In all study patients with late diagnosis, clinical cardiac findings other than systolic murmurs were present that should have alerted the physician on the possible presence of underlying heart disease. Received: 30 June 2000 / Accepted: 15 December 2000     

Effects of pentoxifylline (trental) on blood flow,viscosity, and oxygen transport in young adults with inoperable cyanotic congenital heart disease

Summary Four polycythemic young adults with inoperable cyanotic congenital heart disease were treated for 12 weeks with 20 mg/kg/day of pentoxifylline in an attempt to increase pulmonary blood flow by improving red blood cell demorability and decreasing whole blood viscosity. Treatment caused a rise in mean arterial oxygen saturation from 75–82%, a fall in the mean oxygen extraction coefficient from 47–40%, and a fall in mean oxygen consumption from 186–169 ml/min/m². Pentoxifylline decreased whole blood, but not plasma, viscosity at all hematocrits over a range of shear rates. Two patients had significant bleeding episodes during treatment.     

Wheezing as a sign of cor triatriatum sinister culminating in multiple organ failure

Cardiac asthma or cardiac wheezing (CW) refers to a syndrome of dyspnea and wheezing that mimicks asthma clinically. Reported herein is the case of a 2‐month‐old boy who presented with refractory wheezing as a sign of cor triatriatum sinister (CTS) that culminated in overwhelming multiple organ failure in a short time. On the day of admission, oxygen saturation (SpO₂) was <80%. Heart rate was 198 beats/min and respiratory rate 58 breaths/min. Chest radiogram showed pulmonary edema. Electrocardiogram showed right atrial enlargement and right ventricular hypertrophy. N‐terminal pro‐brain natriuretic peptide (NTproBNP) was very high at >20 000 pg/mL. Two‐dimensional echocardiography with Doppler showed CTS, which was complicated with severe pulmonary arterial hypertension due to flagrant pulmonary venous obstruction. Cardiac surgery was undertaken, after which pulmonary edema subsided, SpO₂ increased to ≥96%, and NTproBNP dropped to normal. He was discharged 11 days later, and was free of cardiac, pulmonary, renal, and neurological sequelae at 24 month follow up.     

Increased turnover of serotonin in children with pulmonary hypertension secondary to congenital heart disease

Serotonin (5HT) is a potent vasoconstrictor of the pulmonary vascular bed and may be involved in the pathophysiology of secondary pulmonary hypertension in children with a left-to-right shunt due to a congenital heart defect. To test this hypothesis we measured the total and free 5HT concentration in blood as well as the urinary excretion of its main metabolite 5-hydroxyin-doleacetic acid (HIAA) in children showing a left-to-right shunt with (n=10) and without (n=18) pulmonary hypertension. 5HT and HIAA were also measured in children after corrective cardiac surgery using cardiopulmonary bypass (n=14) and in controls without congenital heart disease (n=18). The concentrations of total and free 5HT were not significantly different between controls and patients with a left-to-right shunt. After cardiac surgery total 5HT concentration was significantly reduced by about 65% owing to a postoperatively reduced platelet count. In patients with a left-to-right shunt the total 5HT content was similar in the right atrium (204.0±17.3 ng/ml), pulmonary artery (189.0±19.1 ng/ml), and aorta (195.0±19.3 ng/ml), as was the free 5HT concentration. Therefore no net release of 5HT from platelets occurred between these sampling sites. In patients with pulmonary hypertension, the urinary excretion of HIAA was significantly increased when compared with controls and patients without pulmonary hypertension. It is concluded that turbulent blood flow in children with a left-to-right shunt does not lead to a significant release of 5HT from platelets. However, the increased urinary excretion of HIAA in patients with pulmonary hypertension indicates an increased turnover of 5HT, probably due to an increased number of intrapulmonary neuroepithelial cells or a higher metabolic rate of 5HT within those cells.