Autonomic responses to sighs in healthy infants and in victims of sudden infant death

doi:10.1016/S1389-9457(03)00107-2

Sleep Medicine

Volume 4, Issue 6, November 2003, Pages 569-577

https://doi.org/10.1016/S1389-9457(03)00107-2 Get rights and content

Abstract

Objective

Sigh, defined as an isolated breath with an increased tidal volume, can be associated with abrupt changes in heart rate (HR) or blood oxygenation. Sigh may be followed by a central apnea. As impairment of autonomic control was postulated in future SIDS victims, we hypothesized that their autonomic responses to sighs were different from those of healthy control infants.

Methods

Sighs followed by central apnea were studied in the sleep recordings of 18 infants who eventually died of SIDS and of 18 control infants. The infants of the two groups were matched for sex, gestational age, postnatal age, weight at birth and sleep position during sleep recording. HR autoregressive power spectral analysis was performed on RR intervals preceding and following sighs.

Results

In all infants, most sighs followed by an apnea were found in NREM sleep. Compared to the control infants, the future SIDS victims were characterized by a greater sympathovagal balance and a lower parasympathetic tonus before the sighs. Following the sighs, no more differences were found in NREM sleep.

Conclusion

Based on the present findings, it can be postulated that sighs contribute to reset autonomic tonus during NREM sleep.

Introduction

Sighs are initiated by an inspiration-augmenting reflex arising in vagal afferents, probably from stimulations of rapidly adapting pulmonary mechanoreceptors [1] or of peripheral chemoreceptors [2]. The increased afferences to the respiratory brainstem system may also have an influence on the cardiovascular brainstem, reducing the vagotonus and causing acceleration of heart rate (HR) [3]. The apnea following sigh may be secondary to a rapid decline in carotid body chemoreceptor afferent discharge, due to a sigh-induced increase in arterial oxygen concentration and pH and a decrease in carbon dioxide [4], [5]. During the ensuing apnea, the vagal inhibition is liberated.

These large breaths occur spontaneously or can induced by lung inflation or airway occlusion [6]. Sighs contribute to open collapsed alveoli, increase pulmonary compliance and functional residual capacity, and prevent atelectasis [7].

Study of autonomic response following a sigh could be a single tool for diagnosis of autonomic dysfunction. Using a Laser Doppler flowmeter to measure the cutaneous vasoconstriction after spontaneous sigh, Galland et al. confirmed a reduced autonomic activity in healthy infants positioned prone to sleep [8]. Changes in cardiac autonomic controls were seen in infants sleeping prone [8], [9], prenatally exposed to cigarette smoke [10], or in high ambient temperature [11]. These conditions, known to increase the risk of sudden infant death syndrome (SIDS), were all associated with a reduced parasympathetic activity as measure on the infants’ heart rate (HR) [12], [13], [14], [15]. Evidences of changes in cardiac autonomic controls were collected in infants who eventually died of SIDS. Such changes included high baseline HR [16], small HR variability [17], prolonged Q-Tc indexes [18], low parasympathetic tone and/or high sympathovagal balance [19], [20], [21].

In future SIDS victims, the frequency of sighs followed by an apnea were reported to be reduced, compared to findings in healthy control infants, raising the possibility of lower peripheral chemoreceptor responses [22].

Based on the above observations, we postulated that autonomic responses to spontaneous sighs were depressed in future victims of SIDS.

Section snippets

Patients

Between May 1992 and May 1995, a polygraphic sleep study was performed on 18 infants who later died of SIDS. These recordings were collected from 13 sleep laboratories. The sleep studies were conducted as part of different sleep research programs or to alleviate parental anxiety about sleep apnea. Two studies on autonomic tonus and autonomic responses after obstructive apnea were already published on this database [21], [23]. Of the 18 SIDS, 13 infants were males and six were preterm infants.

Sleep stages

Each record was allocated a random code number. The code was disclosed after completion of the analysis. Two independent scorers analyzed the sleep recordings to ensure reliability. The two scorers had not taken part in the collection of the data and analyzed the coded recordings without knowledge of the patient's identity. Disagreements were discussed and subsequently agreed upon codes were used in data analysis. Each 30-s period of the recordings was analyzed and categorized as either

Results

The general characteristics of the infants studied are reported in Table 1. Due to the study design, no difference was seen between the future SIDS and the control subjects for sex, gestational age, postnatal age, weight at birth and sleeping position. Mothers of the future SIDS victims were younger than those of the control infants (P=0.022). Only one infant died after 6 months of age at 36 weeks.

No significant differences were seen between the two groups of infants for the following sleep

Comparison between REM and NREM sleep

In both future SIDS victims and control infants, comparing NREM sleep to REM sleep, the cardiac parasympathetic activity appeared to be significantly greater, as expressed by differences in high-frequency normalized powers, high frequency bandwidth and the sympathetic tonus lower reflected by LF normalized power and low/high power ratios (Table 4, Table 5). These results were found before and after the sighs. After the end of apnea following the sigh, the percent heart rate decrease was higher

Discussion

Compared to the control infants, future SIDS victims had lower values of HF normalized powers and higher LF/HF power ratios in all sleep stages. These differences were, however, not seen following the sighs in NREM sleep. It can be hypothesized that autonomic reactions following the sighs were different in NREM and REM sleep. The sighs could thus contribute to reset the autonomic tonus in NREM sleep.

We must admit several limitations to the present study. First, we could not measure tidal volume

Acknowledgements

The authors gratefully acknowledge the physicians of the 12 other sleep units for their collaboration: F. Alu (St. Elizabeth), F. Ravet (Citadelle), F. Lemmens (St Jans Ziekenhuis), M. Foulon (Hôpital Civil), Y. Vandeplas (AZ VUB), F. Van Horebeke (Onze Lieve Vrouw), R. Vinckx (Imelda Ziekenhuis), J. Barillari (Kiniek Maria Midelares), R. Marien (HZ St Augustinus), F. Deneyer (Vilvoorde Ziekenhuis), J. Van Egemont (UZ Gent), F. Michel (Cliniques St Pierre).

References (53)

M. Glogowska et al.
The rate of vagus nerves, peripheral chemoreceptors and other pathways in the genesis of augmented breaths in cats and rabbits
Respir Physiol
(1972)
B. Galland et al.
Vasoconstriction following spontaneous sighs and head-up tilts in infants sleeping prone and supine
Early Hum Dev
(2000)
D.H. Kelly et al.
Pneumograms in infants who subsequently died of the sudden infant death syndrome
J Pediatr
(1986)
G. Baselli et al.
Spectral and cross-spectral analysis of heart rate and arterial blood pressure variability signals
Comp Biomed Res
(1986)
S.W. Porges
Cardiac vagal tone: a physiological index of stress
Neurosci Biobehav Rev
(1995)
J.J. Quattrochi et al.
Brainstem immaturity in sudden infant death syndrome: a quantitative rapid golgi study of dendritic spines in 95 infants
Brain Res
(1985)
M.G. Larrabee et al.
Excitation and inhibition of phrenic neurones by inflation of the lungs
Am J Physiol
(1946)
M. Eiselt et al.
Sigh-related heart rate changes during sleep in premature and full-term newborns
Neuropediatrics
(1992)
R. Perez-Padilla et al.
Sighs during sleep in adult humans
Sleep
(1983)
P. Fleming et al.
The development of stability of respiration in human infants: changes in ventilatory responses to spontaneous sighs
J Physiol
(1984)

P. Franco et al.

Decreased autonomic responses to obstructive sleep events in future victims of sudden infant death syndrome

Pediatr Res

(1999)

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Original articleAutonomic responses to sighs in healthy infants and in victims of sudden infant death

Abstract

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Patients

Sleep stages

Results

Comparison between REM and NREM sleep

Discussion

Acknowledgements

Respir Physiol

Early Hum Dev

J Pediatr

Comp Biomed Res

Neurosci Biobehav Rev

Brain Res

Excitation and inhibition of phrenic neurones by inflation of the lungs

Am J Physiol

Sigh-related heart rate changes during sleep in premature and full-term newborns

Neuropediatrics

Sighs during sleep in adult humans

Sleep

The development of stability of respiration in human infants: changes in ventilatory responses to spontaneous sighs

J Physiol

Sighs and their relationship to apnea in the newborn infant

Biol Neonate

Different patterns of sighs in neonates and young infants

Biol Neonate

Interaction between bedding and sleeping position in the sudden infant death syndrome: a population based case-control study

Br Med J

Smoking and the sudden infant death syndrome

Pediatrics

Thermal environment and sudden infant death syndrome: case-control study

Br Med J

Prone sleep and decreased cardiorespiratory response to auditory stimulation in healthy infants

Pediatrics

Sleep position, autonomic function and arousal

Arch Dis Child Neonatal

Influence of maternal smoking on autonomic nervous system in healthy infants

Pediatr Res

Influence of ambient temperature on sleep characteristics and autonomic nervous control in healthy infants

Sleep

Cardiac and respiratory patterns in normal infants and victims of the sudden infant death syndrome

Sleep

Prolongation of the QT interval and the sudden infant death syndrome

N Engl J Med

Spectral analysis assessment of respiratory sinus arrhythmia in normal infants and infants who subsequently died of sudden infant death syndrome

Pediatr Res

New findings in the analysis of the heart rate variability in infants

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Polysomnographic study of autonomic nervous system in potential victims of sudden infant death syndrome

Clin Autonom Res

Polysomnographic studies of infants who subsequently died of sudden infant death syndrome

Pediatrics

Decreased autonomic responses to obstructive sleep events in future victims of sudden infant death syndrome

Pediatr Res

Original article
Autonomic responses to sighs in healthy infants and in victims of sudden infant death