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Archives of cardiovascular diseases
Volume 103, n° 8-9
pages 430-436 (août 2010)
Doi : 10.1016/j.acvd.2010.07.002
Received : 11 December 2009 ;  accepted : 2 July 2010
Correlations between urinary excretion of catecholamines and electrocardiographic parameters of vagal hyperreactivity in infants with fainting spells. Implication of sympathetic hypotonia?
Corrélations entre les excrétions urinaires des catécholamines et les paramètres électrocardiographiques de l’hyperréactivité vagale chez des nourrissons présentant des malaises. Implication d’une hypotonie sympathique ?
 

Claire-Odile Leroy-Bouchereau a, Paul Urios a, e, Anne-Marie Borsos a, f, Samir Nakib d, Sylvie Escolano g, Vincent Lucet c, Michel Sternberg a, b,
a Équipe de recherches sur la biochimie et la pharmacologie des vaisseaux et du rein, laboratoire de pharmacologie, faculté de pharmacie, 4, avenue de l’Observatoire, 75006 Paris, France 
b Laboratoire de biochimie, hormonologie et métabolisme, hôpital Saint-Vincent-de-Paul, 82, avenue Denfert-Rochereau, 75014 Paris, France 
c Centre de cardiologie infantile du Château-des-Côtes, 78350 Les-Loges-en-Josas, France 
d Laboratoire de biochimie A, Hôtel-Dieu, 75004 Paris, France 
e Laboratoire d’hormonologie et de génétique, hôpital Bichat, 75018 Paris, France 
f Laboratoire de biochimie, hormonologie et génétique, hôpital Ambroise-Paré, 92100 Boulogne-Billancourt, France 
g Équipe de biostatistiques, centre de recherches en épidémiologie et santé des populations, hôpital Paul-Brousse, Villejuif, France 

Corresponding author. Fax: +33 (0)1 46 61 87 98.
Summary
Background

Vagal hyperreactivity (VHR) is a frequent etiology of infant fainting spells; but it is sometimes difficult to diagnose. A biochemical test would therefore be useful, especially as the oculocardiac reflex (OCR) test innocuity is not absolute.

Aims

To evaluate urinary excretions of norepinephrine, epinephrine and dopamine as markers for vagal hyperreactivity.

Methods

During check-up of 55 infants from 0.5 to 11months of age, for discomfort episodes, including OCR and Holter recording, 24h urinary assays of total norepinephrine, epinephrine and dopamine were carried out to evaluate sympathetic activity.

Results

Epinephrine and norepinephrine urinary excretions were negatively correlated with VHR intensity, as measured by the OCR ECG parameters: RRmax, % cardiac deceleration and minimal frequency; dopamine excretion was not. When RRmaxOCR was greater or equal to 800ms, epinephrine urinary excretion tended to be less or equal to 9nmol/mmol creatinine and norepinephrine excretion less or equal to 190nmol/mmol creatinine.

Conclusion

A delay in maturation of the sympathetic system and/or adrenomedullary glands with low secretion of norepinephrine and epinephrine inducing a desequilibrium of the sympathetic/parasympathetic balance may contribute to the fainting spells observed with VHR. Epinephrine and norepinephrine urinary excretions may provide informative complementary noninvasive markers for VHR.

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Résumé
Justification

L’hyperréactivité vagale (HRV) est une étiologie fréquente des malaises chez le nourrisson; son diagnostic est parfois difficile. Un test biochimique serait donc utile, d’autant que l’innocuité de l’épreuve du reflexe oculocardiaque (ROC) n’est pas absolue.

Objectif

Répondre à la question: les excrétions urinaires de noradrénaline, adrénaline et dopamine sont-elles marqueurs d’HRV ?

Méthodes

Les excrétions urinaires de noradrénaline, adrénaline et dopamine totales de 24heures ont été mesurées pour évaluer l’activité sympathique chez 55 nourrissons de 0,5 à 11mois présentant des malaises et soumis au bilan habituel clinique et électrocardiographique incluant le ROC et l’enregistrement Holter de 24heures.

Résultats

Les excrétions urinaires d’adrénaline et noradrénaline sont négativement corrélées avec l’intensité d’HRV appréciée par les paramètres électrocardiographiques du ROC: RRmax, pourcentage de décélération et fréquence minimale cardiaques. Lorsque RRmax au ROC est supérieur ou égal à 800ms, l’excrétion nycthémérale d’adrénaline tend à être inférieure ou égale à 9nmol/mmol de créatinine, celle de noradrénaline inférieure ou égale à 190nmol/mmol de créatinine.

Conclusion

Un retard de maturation du système sympathique et/ou des médullosurrénales avec hyposécrétion de noradrénaline et d’adrénaline entraînant un déséquilibre de la balance parasympathique/sympathique pourrait contribuer aux malaises associés à une HRV. Les excrétions nycthémérales d’adrénaline et noradrénaline pourraient constituer des marqueurs complémentaires intéressants et non invasifs d’HRV.

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Keywords : Vagal hyperreactivity, Infant fainting spells, Urinary norepinephrine, epinephrine and dopamine, Oculocardiac reflex, Holter ECG, Sudden infant death syndrome

Mots clés : Hyperréactivité vagale, Malaises du nourrisson, Noradrénaline, adrénaline et dopamine urinaires, Réflexe oculocardiaque, Holter, Syndrome de mort subite du nourrisson

Abbreviations : ALTE, Cr, D, E, ECG, F min, ΔFi, HR, Log, NE, OCR, RR max, SIDS, U, VHR


Introduction

Vagal hyperreactivity (VHR) is a frequent etiology in infant fainting spells or in apparent life threatening events (ALTE). It appears isolated, without any other cause of fainting spell, in about 12 to 15% of all cases [1]. It is more frequently found in association with gastro-esophagal reflux. VHR is also associated with reflex anoxic seizures (white breath-holding) [2]. It is suspected to participate in the etiology of sudden infants death syndrome (SIDS) [3, 4, 5, 6, 7].

Even though VHR is that frequent and systematically investigated for infant discomfort evaluation in our centre of infant cardiology, it is still difficult to diagnose and even controversial. Diagnosis relies on a stack of clinical, historical and electrocardiographic arguments. Two complementary tests currently used for that purpose in infants are oculocardiac reflex (OCR) and 24-h Holter ECG [4, 6, 7]. But normal limits for these two tests, particularly for OCR, are discussed and falsely negative results were reported with secondary evidence of VHR [4]. Furthermore, the innocuity of OCR is not absolute. Besides infant relapsing fainting spells with VHR may be treated by atropinic drugs [8]. We thought that complementary biochemical tests exploring the sympathetic and parasympathetic nervous systems would be welcome for the diagnosis, the follow-up under treatment and a better comprehension of the physiopathology of VHR. Since noninvasive, urinary tests are preferred in infants.

In a previous experimental study, we observed a decrease in norepinephrine (NE) urinary excretion (U) in rats with experimental vagal hypertonia induced by reserpine. Opposite variations were found in a model of vagal hypotonia induced by diphemanil-methylsulfate [9].

We therefore determined UNE, but also U epinephrine (E) and U dopamine (D) in infants with fainting spells who were tested for VHR.

Subjects and methods
Subjects

Fifty-five infants from 0.5 to 11months of age were investigated at the “Centre de cardiologie infantile du Château-des-Côtes” for VHR, 51 after fainting spells, four as siblings of SIDS victims. The investigation includes routinely, besides the history and the clinical examination, OCR and 24-h Holter ECG [6]. At the end of the evaluation, diagnosis was established, ranging from frank VHR (score 4) to absence of VHR (score 1). Positive diagnosis of VHR (score 4) is admitted in the presence of one major criterium, or three minor criteria. Possible VHR (score 3) or doubtful VHR (score 2) are considered in the presence of two minor criteria or one minor criterion respectively.

Major criteria:

fainting or syncope during the Holter ECG monitoring with a simultaneous prolonged sinus pause;
inducibility of fainting or syncope during OCR reproducing the same type of faint described by the family.

Minor criteria:

history of familial VHR;
identification of vagally mediated signs induced by factors like pain, vomiting, crying;
clinical symptoms such as pallor, hypotonia, cyanosis of the lips;
positive OCR test or indexes of VHR on the Holter recording.

The study complied with the Helsinki declaration. After informed and written consent of the parents, as recommended by Huriet Law, two consecutive noninvasive urinary collections were carried out. A urinary bag was installed for a 3-h collection starting between 9h and 10h30a.m. just after the clinical examination and the OCR test; then a 21-h collection followed immediately and covered the whole night period. Results for 24h were obtained by calculation. This protocol was established to test the diagnostic value of the 3-h versus the 24-h collection.

Electrophysiological cardiac parameters

The quantitative parameters of OCR were studied as in [5, 6, 10]:

minimum heart rate (FminOCR ), calculated on three successive beats, expressed as beats per minute (bpm);
RRmaxOCR (maximum interval between two R waves, in ms);
ΔFiOCR , percentage of heart rate (HR) deceleration:
ΔFi=[(HR before the test – HR during the test)/HR before the test]×100.

Evident VHR criteria under 3months are: FminOCR 50bpm, RRmaxOCR 1200ms or ΔFiOCR 66%.

Moderate VHR criteria under 3months are: FminOCR 75bpm, RRmaxOCR 800ms or ΔFiOCR 50%.

The Holter quantitative parameters were [4, 6]:

FminHolter , minimum cardiac frequency observed during the 24h (in bpm);
ΔFiHolter , maximal deceleration upon 10s, observed during the 24h.

VHR criteria are FminHolter 80bpm under 1month, ≤70bpm under 2months, ≤60bpm between 2months and 1year, or ΔFiHolter 55% or ΔFiHolter 100bpm absolute deceleration.

Urinary collection and biochemical assays

Urine collection was carried out after addition of 0.5mL of HCl for 3h and 2mL for 21h in the storage bottles, kept at 4°C during the collection and frozen at −30°C thereafter. Urine acidity was checked (pH between 1 and 3).

Total norepinephrine, epinephrine and dopamine (free and conjugated) were measured by high performance liquid chromatography (HPLC) in reverse phase with amperometric electrochemical detection, after hydrolysis (20min at 80°C, at a pH of 0.8 to 1) and extraction by ionic exchange on Biorad column [9].

Creatinine (Cr) was determined by the Jaffé method on KONE “Optima” analyzer. The first 20 samples were measured with and without previous pH neutralization. The results obtained were similar. Therefore pH neutralization was omitted further on.

All results of biochemical assays of catecholamines were expressed as nmol per mmol Cr.

Statistical methods

In the whole group infants from 0.5 to 11months or in different groups of age, the urinary excretions of the different catecholamines are represented by the mean±SD and/or the (range). Loge of the values was used to normalize their distribution if necessary.

For studying correlations between urinary excretion of each catecholamine and A37 age or electrocardiographic parameters, Pearson’s correlation as well as multiple correlation coefficients were determined, using the statistical Analysis System SAS 9.2 software (SAS Institute Inc, Cary, NC, USA) with the CORR procedure; adjustment for age was effected by the REG procedure (0 if ≤3months, 1 if >3months, since 3months of age has been found to be a critical milestone, see discussion).

For studying the variations of excretion of each metabolite in function of age (age sections of 1month) or collection time (3h/21h) or VHR score (1 to 4), analysis of variance was used, followed by comparison of means by the Bonferoni-Student t test.

The level of significance was considered as P 0.05.

Results
Clinical characteristics of the infants
Age

Out of 55 infants, six were under 1month (0.5 to 0.9months), 15 from 1.0 to 1.9months, 18 from 2.0 to 2.9months, eight from 3.0 to 3.9months, three from 4.0 to 4.9months, five older than 5months (5.3, 7.6, 9.5, 10, 10.3). Five children were preterms, (30 to 36weeks). Maturation of the cardiac control being in relation with the gestational age [11], we used for these children an A37 age, as if they had been born at 37weeks. Eighty-five percent of the children had their first fainting spell before 3months of age.

Diagnosis of VHR

Sixteen children had positive VHR (score 4), 15 possible VHR (score 3), nine doubtful VHR (score 2), 15 absence of VHR (score 1). None of the four siblings of SIDS victims had VHR.

Urinary epinephrine
Variations of excretion in function of age or collection time

For the infants of all ages, the mean UE24h =14.8±10.1nmol/mmolCr (with high individual variations, from 1 to 43.8nmol/mmolCr). In contrast with norepinephrine excretion (see below), neither UE24h nor LogUE24h were correlated with the A37 age (r =0.077 and r =0 respectively).

For what concerns the effect of collection time, UE21h was lower than UE3h only in children aged less than 2months (8.7±5.6nmol/mmolCr vs 24.4±24.2nmol/mmolCr, P <0.005). Beyond 2months of age, the difference disappeared.

Correlations with OCR ECG parameters

In all children between 0.5 and 11months, LogUE24h was negatively correlated with RRmaxOCR (r =−0.34; P =0.012), positively correlated with FminOCR (r =+0.31; P =0.024), marginally correlated with ΔFiOCR (r =−0.24; P =0.084) (Table 1).

When adjusted for age, the previous correlations were not markedly modified (for example, P =0.014, instead of P =0.012, for the correlation between LogUE24h and RRmaxOCR ).

When the three OCR ECG parameters used for the diagnosis of VHR were taken together in a multiple correlation, LogUE24h was highly correlated with the three parameters (r =|0.36|; P =0.009).

Figure 1 shows the individual results for RRmaxOCR and the correlation curve obtained. The latter shows that when RRmaxOCR is greater or equal to 800ms, LogUE24h tends to be less or equal to 2.2 and consequently UE24h tends to be less or equal to 9nmol/mmolCr.



Figure 1


Figure 1. 

A. Correlation between Loge (epinephrine) and RRmax on ECG recording during oculocardiac reflex for detecting vagal hyperreactivity, in infants with fainting spells (0.5 to 11months old). r =−0.34; P =0.012. B. Correlation between Loge (norepinephrine) and RRmax on ECG recording during oculocardiac reflex for detecting vagal hyperreactivity, in infants with fainting spells (0.5 to 11months old). r =−0.25; P =0.06. Loge (norepinephrine) was significantly correlated with the three OCR ECG parameters of VHR (RRmax, Fmin and % deceleration) taken together in a multiple correlation (r =|0.33|; P =0.015).

Zoom

Correlations with Holter ECG parameters

We found no correlation between LogUE24h and the Holter ECG parameters, whatever the age (Table 1).

Studies of correlations with UE3h

Studies of correlations with UE3h were unsuccessful, partly because of the great variability of spontaneous urine collection volume, during this short period. The same will apply for UNE3h and UD3h .

Urinary norepinephrine
Variations of excretion in function of age or collection time

For all the infants aged from 0.5 to 11months, the mean UNE24h was 229±104nmol/mmolCr (30.0 to 468nmol/mmolCr); UNE24h was correlated with the A37 age (r =−0.26, P =0.05); LogUNE24h was more tightly correlated with the A37 age (r =−0.30, P =0.027).

UNE24h was higher in infants under 3months (259±107nmol/mmolCr) than in infants greater or equal to 3.0months (179±94nmol/mmolCr), P <0.005.

For what concerns the effect of collection time, in the children under 3months, UNE21h was lower than UNE3h (248±70 vs 408±197nmol/mmolCr, P <0.001). Beyond 3months, the significance of the difference disappeared (180±100 vs 211±105nmol/mmolCr).

Correlations between UNE24h and OCR ECG parameters

In all the infants from 0.5 to 11months, LogUNE24h was significantly correlated with the three OCR ECG parameters of VHR taken together in a multiple correlation (r =|0.33|; P =0.015) (Table 1).

When the OCR ECG parameters were considered separately, LogUNE24h was marginally correlated with RRmaxOCR (r =− 0.25; P =0.06), but not correlated significantly either with FminOCR (r =+0.19; P =0.17) or with ΔFiOCR (r =−0.11; P =0.41).

When adjusted for age, the previous correlations were not markedly modified.

Figure 1 shows the individual results for RRmaxOCR and the correlation curve obtained. The latter shows that when RRmaxOCR is greater or equal to 800ms, LogUNE24h tends to be less or equal to 5.24 and UNE24h tends to be less or equal to 190nmol/mmolCr.

Correlations between UNE24h and Holter ECG parameters

No correlation was found between LogUNE24h and FminHOLTER or ΔFi HOLTER (Table 1).

Urinary dopamine
Variations of excretion in function of age or collection time

For the infants of all ages, the mean UD24h =2651±1063nmol/mmolCr (77 to 6190nmol/mmolCr). UD24h /Cr did not vary significantly with age. UD21h /Cr was lower than UD3h /Cr until 3months of age, the difference reaching significance in children between 2 and 3months (P <0.025).

Correlations with OCR ECG parameters

In all the infants from 0.5 to 11months, UD24h was not correlated with RRmax (P =0.90), with FminOCR (P =0.76) or with ΔFiOCR (P =0.47) (Table 1).

Correlations with Holter ECG parameters

No significant correlation was found between UD24h and FminHOLTER (P =0.88) or ΔFi HOLTER (P =0.13) in the infants from 0.5 to 11months (Table 1).

Discussion

The various studies previously published about the urinary excretion of the different catecholamines in children aimed essentially at establishing normal ranges to track down neuroblastomas [12, 13, 14, 15, 16, 17]. In this prospect, the authors sought essentially to establish higher limits. No lower limits were generally given. For each catecholamine studied, our results are in agreement with those previously published. We also confirmed a strong interindividual variability. To our knowledge, no study described the evolution of catecholamine urinary excretion in infants under 1year. Decrease of UNE/Cr after 3months has not been reported. The circadian differences we observed (higher excretions in the morning during the 3-h collection, before 3months for NE and D and before 2months for E) had not been described before. We must notice that the morning time collection corresponded, in our study, to a period of stress: clinical examination, OCR, setting of Holter electrodes and urinary bag. Besides, one must recall that the infants studied here had presented fainting spell(s).

Our study of the correlations between the quantitative urinary excretion of cathecholamines and quantitative ECG parameters in infants with fainting spell(s), is in fact independent of the qualitative diagnosis of VHR in the various individuals, which may be sometimes difficult (in case of scores 2 or 3: possible or doubtful VHR). The ECG parameters measured during the OCR were generally found to be more strongly correlated with urinary excretion of cathecholamines than the ECG parameters measured on the Holter recording.

UE24h was negatively correlated with VHR intensity, as measured by OCR ECG parameters. Indeed, in the case of frank VHR, FminOCR decreases, RRmax and ΔFiOCR increase. In this situation, we generally observed a diminution of UE. When UE24h is less or equal to 9nmol/mmolCr, RRmax tends to be greater or equal to 800ms (Figure 1) and Fmin less or equal to 70bpm. Low UE could be a useful auxiliary marker for VHR.

UNE24h was also negatively correlated with VHR intensity as represented by the three OCR ECG parameters taken together and also particularly by RRmaxOCR alone. If UNE24h is less or equal to 190nmol/mmolCr, RRmax tends to be greater or equalt to 800ms. Low UNE24h could be another marker for VHR.

These results suggest the possible contribution of sympathetic hypotonia and/or adrenomedullary hyposecretion in the physiopathology of faintings associated with VHR.

Our findings are in accordance with our previous experimental observations [9]: diminution of UNE in rats with pharmacological parasympathetic hypertonia (−44%) and increase in UNE in rats with parasympathetic hypoactivity (+61%).

At the critical age of 3months, UNE24h decreases and its significant circadian modifications tend to disappear in our study. At the same period, heart rate starts to diminish, with a more significant reduction during daytime [18]. In this study, the age of 71% of the infants was less or equal to 2.9months, that of 15% between 3 and 3.9months; 85% of the infants had their first fainting spell before 3.0months of age. Moreover, SIDS incidence curve shows a peak at about 3months. SIDS may be related to VHR. Several cases of SIDS were observed in infants having noradrenergic deficits [19]; these deficits were alterations of catecholaminergic neurons [20, 21, 22], alterations in catecholamine enzymes [21, 23, 24] or alterations in alpha2-adrenergic receptors [25].

For what concerns the possible use of UE24h and UNE24h as markers for VHR, it must be stressed that it is difficult to determine their sensitivity and specificity since the diagnosis of VHR is greatly clinical. Another difficulty is due to the existence of three classes of infants: one class of infants with positive VHR (28% of the infants with score 4), one class with absent VHR (28% of the infants with score 1), but also a third class with uncertain VHR (44% of the infants with possible or doubtful VHR corresponding to scores 3 or 2); the latter class, which represents almost one half of the whole group of infants, cannot be used for determining a sensitivity and a specificity.

In our study, UE24h appeared as a more promising marker than UNE24h . In the infants from 0.5 to 11months, the mean LogUE24h was 2.74, 2.29 and 2.20 (corresponding to UE24h of 15.5, 9.9 and 9.0nmol/mmolCr) for scores 1, (2+3) and 4 respectively (not significant). At the critical age between 1 and 3months, the mean LogUE24h was 2.73, 2.28 and 2.04 (corresponding to UE24h of 15.3, 9.8 and 7.7nmol/mmol Cr) for scores 1, (2+3) and 4 respectively (not significant); however at this critical age, 50% of infants with score 4 had a UE24h less or equal to 9nmol/mmolCr whereas no infant with score 1 had a UE24h less or equal to 9nmol/mmol Cr. A more extensive study is necessary to test the interest of UE24h and UNE24h as markers for VHR.

Conflict of interest statement

No conflict of interest.


Acknowledgements

We thank J. Garaud, N. Mercier, the medical and paramedical clinical team of the Centre de cardiologie infantile du Château-des-Côtes, for their collaboration; Jean-Pascal Debandt and Luc Cynober for supervising the determination of catecholamines at the biochemistry laboratory of Hôtel-Dieu Hospital; J. Lellouch and J. Peyroux for useful discussion.

Funding : We thank Paris-6 University, “Naître et Vivre, association pour la prévention de la mort subite du nourrisson” and “Naturalia et Biologia”.

References

Challamel M.J. Malaise grave du nourrisson Neurologie pédiatrique Paris: Flammarion (1998).  485-492
Stephenson J.P.B. Reflex anoxic seizure (white breath-holding): nonepileptic vagal reflex Arch Dis Child 1978 ;  53 : 193-200 [cross-ref]
Ledwidge M., Fox G., Matthews T. Neurocardiogenic syncope: a model for SIDS Arch Dis Child 1998 ;  78 : 481-483 [cross-ref]
Lucet V., Chéron G. Exploration des anomalies du rythme cardiaque Progrès en pédiatrie. La mort subite de nourrisson Paris: Doin (1989).  235-252
Lucet V. Arythmies, système nerveux autonome et mort subite du nourrisson Progrès en néonatologie Basel: Karger (1990).  156-163
Lucet V., de Bethmann O., Denjoy I. Paroxysmal vagal overactivity. Apparent life-threatening event and sudden infant death Biol Neonate 2000 ;  78 : 1-7 [cross-ref]
Kahn A., Riazi J., Blum D. Oculocardiac reflex in near miss for sudden death syndrome infants Pediatrics 1983 ;  71 : 49-52
Lucet V., Denjoy I., Do Ngoc D., Toumieux M.C., Picard-Claudel M.A., Coumel P. Effet du traitement atropinique sur la mort subite du nourrisson, enquête multicentrique réunissant 7851 enfants à risque Presse Med 1992 ;  21 : 1896-1900
Urios P., Grigorova-Borsos A.M., Mozère G., Nakib S., Dauchy F., Peyroux J., and al. Cyclic guanosylmonophosphate urinary excretion in parasympathicomimetic or parasympathicolytic syndromes induced by reserpine or diphemanil-methylsulfate Life Sci 1999 ;  64 : 113-123
De Broca A., Kremp O., Krim G., Herbaut C., Leke L., Risbourg B. Standardisation du reflexe oculo-cardiaque chez le nourrisson de moins de trois mois Pediatrie 1990 ;  45 : 405-408
Ramet J., Praud J.P., D’Allest A.M., Carofilis A., Dehan M., Guilleminault C., and al. Effect of maturation on heart rate response to ocular compression test during rapid eyes movement sleep in human infants Pediatr Res 1988 ;  24 : 477-480
Fitzgibbon M.C., Tormey W.P. Paediatrics reference ranges for urinary catecholamines/metabolites and their relevance in neuroblastoma diagnosis Ann Clin Biochem 1994 ;  31 : 1-11
Nunez C., Ortiz-Apodaca M.A. Excretion of free catecholamines by children Eur J Clin Chem Clin Biochem 1994 ;  32 : 461-463
Parra A., Ramirez de Angel A., Cervantes C., Sanchez M. Urinary excretion of catecholamines in healthy subjects in relation to body growth Acta Endocrinologica 1980 ;  94 : 546-551 [cross-ref]
Marchese N., Canini S., Fabi L., Famularo L. Paediatric reference values for urinary catecholamines metabolites evaluated by high performance liquid chromatography and electrochemical detection Eur J Chem Clin Biochem 1997 ;  35 : 533-537
Revol A., Comoy E., Forzy G., Garnier J.P., Gerhardt M.F., Hirth C., and al. Méthodes recommandées pour le dosage des catécholamines et de leurs métabolites dans l’urine Ann Biol Clin 1994 ;  52 : 625-637
Rosano T.G. Liquid-chromatographic evaluation of age-related changes in the urinary excretion of free catecholamines in pediatric patients Clin Chem 1984 ;  30 : 301-303
Chéron G., Lucet V., Montgermont P., Couly G. Évolution de la fréquence cardiaque au cours de la première année et malaises du nourrisson Arch Fr Pediatr 1986 ;  43 : 475-479
Hilaire G. Endogenous noradrenaline affects the maturation and function of the respiratory network: possible implication for SIDS Auton Neurosci 2006 ;  126–7 : 320-331 [cross-ref]
Kopp N., Chigr F., Denoroy L., Gilly R., Jordan D. Absence of adrenergic neurons in nucleus tractus solitarius in sudden infant death syndrome Neuropediatrics 1993 ;  24 : 25-29 [cross-ref]
Obonai T., Yasuhara M., Nakamura T., Takashima S. Catecholamine neurons alteration in the brainstem of sudden infant death syndrome victims Pediatrics 1998 ;  101 : 285-288 [cross-ref]
Takashima S., Becker L.E. Delayed dendritic development of catecholaminergic neurons in the ventrolateral medulla of children who died of sudden infant death syndrome Neuropediatrics 1991 ;  22 : 97-99 [cross-ref]
Ozand P.T., Tildon J.T. Alterations of catecholamine enzymes in several brain regions of victims of sudden infant death syndrome Life Sci 1983 ;  32 : 1765-1770 [cross-ref]
Denoroy L., Gay N., Gilly R., Tayot J., Pasquier B., Kopp N. Catecholamine synthesizing enzyme activity in brainstem areas from victims of sudden infant death syndrome Neuropediatrics 1987 ;  18 : 187-190 [cross-ref]
Ozawa Y., Takashima S., Tada H. Alpha2-adrenergic receptor subtype alterations in the brainstem in the sudden infant death syndrome Early Hum Dev 2003 ;  75 (Suppl.) : S129-S138 [cross-ref]



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