[Exercise capacity in children with mild sleep-disordered breathing]. / Capacité physique de l'enfant présentant un syndrome d'apnée du sommeil léger.

INTRODUCTION: While the association between sleep-disordered breathing (SDB) and low physical activity has been reported in children, little information is available on the impact of SDB on exercise capacity. The aim of this study was to assess exercise capacity in children with SDB in order to estimate the relevance of exercise training intervention. METHODS: Twelve young patients with suspected SDB matched with 11 presumably healthy subjects of same age range (aged 13±0.5yr) were investigated. Both groups underwent physical activity assessment, full night polysomnography, incremental and all-out exercise tests. RESULTS: The respiratory disturbance index was higher in the patient group (4.6±4.7 vs 0.8±0.6; P=0.02). Children with SDB had lower VO2max (32.0±9.9 vs 42.3±5.7mL.kg-1.min-1, P=0.007) and lower peak power (8.6±3.4 vs 11.8±1.9W.kg-1, P=0.009). A significant correlation between VO2max and weekly physical activity only was found in the SDB group (P=0.005). CONCLUSION: Mild SDB may be associated with impairment of both aerobic and anaerobic exercise capacity in children, related to poor physical activity. Exercise training could bring clinical benefit in this population.

Active glottal closure during anoxic gasping in lambs.

The present study was aimed at assessing laryngeal dynamics and their consequences during anoxic gasping in ketamine-sedated lambs. We first verified that the glottis was closed between gasps during anoxic gasping in seven chronically instrumented lambs, aged 11-15 days. Recording of glottal constrictor muscle electrical activity, subglottal pressure and lung volume, together with endoscopic observation, confirmed the presence of active glottal closure with maintenance of a high lung volume between gasps. Secondly, we tested whether maintenance of a high lung volume between gasps improved autoresuscitation efficiency. Six sedated lambs aged 8-11 days underwent two anoxic runs, including one with an open tracheostomy to prevent maintenance of a high lung volume. Access back to air was allowed for gasping. No significant difference was found in time to eupnea resumption, hemodynamic parameters or arterial blood gases. We conclude that a high lung volume is actively maintained by glottal closure between anoxic gasps in sedated lambs. Further studies are however needed to define the importance of laryngeal dynamics during gasping.

Consequences of capsaicin treatment on pulmonary vagal reflexes and chemoreceptor activity in lambs.

The aim of this study was to test the hypothesis that capsaicin treatment in lambs selectively inhibits bronchopulmonary C-fiber function but does not alter other vagal pulmonary receptor functions or peripheral and central chemoreceptor functions. Eleven lambs were randomized to receive a subcutaneous injection of either 25 mg/kg capsaicin (6 lambs) or solvent (5 lambs) under general anesthesia. Capsaicin-treated lambs did not demonstrate the classical ventilatory response consistently observed in response to capsaicin bolus intravenous injection in control lambs. Moreover, the ventilatory responses to stimulation of the rapidly adapting pulmonary stretch receptors (intratracheal water instillation) and slowly adapting pulmonary stretch receptors (Hering-Breuer inflation reflex) were similar in both groups of lambs. Finally, the ventilatory responses to various stimuli and depressants of carotid body activity and to central chemoreceptor stimulation (CO(2) rebreathing) were identical in control and capsaicin-treated lambs. We conclude that 25 mg/kg capsaicin treatment in lambs selectively inhibits bronchopulmonary C-fiber function without significantly affecting the other vagal pulmonary receptor functions or that of peripheral and central chemoreceptors.

Radiotelemetry system for apnea study in lambs.

Neonatal apneas are being studied in the laboratory using polysomnographic recordings in lambs. Standard equipment, requiring animal restraint, disrupts sleep and prevents development of spontaneous apneas. The aim of the current work was to develop and validate a wireless recording equipment to study freely moving lambs. Firstly, a radiotelemetry equipment composed of a multichannel FM transmitter and a receiver was developed. Secondly, to test the telemetry equipment, each biopotential - [electroencephalogram (EEG), electrooculogram (EOG), electrocardiogram (ECG), electromyograms (EMGs), nasal airflow] - was recorded simultaneously by standard equipment and by telemetry (5 lambs). The results indicated an excellent concordance between signals obtained by both systems. Finally, the 8-channel telemetry prototype was tested for polysomnographic recordings (16 lambs). Results obtained confirmed the possibility of recording frequent REM sleep periods and spontaneous apneas. In conclusion, this radiotelemetry polysomnographic equipment brings new possibilities for research on neonatal apneas.

Vagal afferents and active upper airway closure during pulmonary edema in lambs.

The present study was undertaken to gain further insight into the mechanisms responsible for the sustained active expiratory upper airway closure previously observed during high-permeability pulmonary edema in lambs. The experiments were conducted in nonsedated lambs, in which airflow and thyroarytenoid and inferior pharyngeal constrictor muscle electromyographic activity were recorded. We first studied the consequences of hemodynamic pulmonary edema (induced by impeding pulmonary venous return) on upper airway dynamics in five lambs; under this condition, a sustained expiratory upper airway closure consistently appeared. We then tested whether expiratory upper airway closure was related to vagal afferent activity from bronchopulmonary receptors. Five bivagotomized lambs underwent high-permeability pulmonary edema: no sustained expiratory upper airway closure was observed. Finally, we studied whether a sustained decrease in lung volume induced a sustained expiratory upper airway closure. Five lambs underwent a 250-ml pleural infusion: no sustained expiratory upper airway closure was observed. We conclude that 1) the sustained expiratory upper airway closure observed during pulmonary edema in nonsedated lambs is related to stimulation of vagal afferents by an increase in lung water and 2) a decrease in lung volume does not seem to be the causal factor.

Effects of capsaicin pretreatment on expiratory laryngeal closure during pulmonary edema in lambs.

The present study, performed in nonsedated, conscious lambs, consisted of two parts. In the first part, we 1) examined for the first time whether a respiratory response to pulmonary C-fiber stimulation could be elicited in nonsedated newborns and 2) determined whether this response could be abolished by capsaicin pretreatment. Then, by using capsaicin-desensitized lambs, we studied whether pulmonary C fibers were involved in the sustained, active expiratory upper airway closure previously observed during pulmonary edema. Airflow and thyroarytenoid and inferior pharyngeal constrictor muscle electromyographic activities were recorded. In the first set of experiments, a 5-10 microg/kg capsaicin bolus intravenous injection in seven intact lambs consistently led to a typical pulmonary chemoreflex, showing that C fibers are functionally mature in newborn lambs. In the second series of experiments, eight lambs pretreated with 25-50 mg/kg subcutaneous capsaicin did not exhibit any respiratory response to 10-50 microg/kg intravenous capsaicin injection, implicating C fibers in the response. Finally, in the above capsaicin-desensitized lambs, we observed that halothane-induced high-permeability pulmonary edema did not cause the typical response of sustained expiratory upper airway closure seen in the intact lamb. We conclude that functionally mature C fibers are present and responsible for a pulmonary chemoreflex in response to capsaicin intravenous injection in nonsedated lambs. Capsaicin pretreatment abolishes this reflex. Furthermore, the sustained expiratory upper airway closure observed during halothane-induced pulmonary edema in intact nonsedated lambs appears to be related to a reflex involving stimulation of pulmonary C fibers.

Thyroarytenoid muscle electrical activity during spontaneous apneas in preterm lambs.

Laryngeal dynamics plays a major role during perinatal life, a period of respiratory control immaturity. Continuous electromyographic (EMG) activity of a laryngeal adductor muscle (thyroarytenoid [TA] muscle), was recently observed throughout provoked central apneas, either isolated or during induced periodic breathing, in full-term lambs. The aim of the present study was to test if continuous TA EMG activity was also present during spontaneous apneas in nonsedated preterm lambs. We studied 7 premature lambs (term 131 +/- 1 d of postconceptional age). Premature birth was induced after acceleration of fetal lung maturation. Electrodes for diaphragm, inferior pharyngeal constrictor (IPC), and TA electromyograms, electrocardiogram, electroencephalogram, eye movement, and airflow recordings were implanted. Radiotelemetry recordings were repeated from 135 to 149 +/- 8 d of postconceptional age. A total of 2,088 apneas (2,020 central and 68 mixed) >/= 3 s were recorded in the lambs, including 57 epochs of periodic breathing. Continuous TA EMG activity was present throughout 88.4% of all apneas and 98.4% of apneas during periodic breathing, regardless of the sleep stage. These results suggest that active glottic closure is frequent during spontaneous central apneas in this model of prematurity. This unique model will allow us to study controlling mechanisms and consequences of glottic closure during neonatal apneas.

Larynx and neonatal apneas.

This paper summarizes current knowledge on laryngeal dynamics during neonatal apneas, including mechanisms potentially involved in mixed/obstructive apneas at the laryngeal level, and recent personal data on active glottic closure throughout spontaneous central apneas (either isolated or in periodic breathing) observed in preterm lambs. It is suggested that this is reminiscent of the basic respiratory pattern in vertebrates alternating periods of lung ventilation with periods of breath-holding with the exchanger full of gas. Moreover, this unique ovine model of spontaneous neonatal apneas and periodic breathing offers new opportunity for studying candidate treatments of neonatal apneas.

Complete glottic closure during central apnea in lambs.

OBJECTIVE: The objectives of this study were threefold: to document complete glottic closure during artificially induced central apnea in lambs; to unequivocally confirm that thyroarytenoid muscle electrical activity during central apneas in lambs reflects complete glottic closure; and to evaluate the physiologic significance of this phenomenon in artificially induced central apneas in lambs. METHODS: We recorded thyroarytenoid (TA) muscle EMG, subglottic pressure, and lung volume simultaneously with direct endoscopic vision of the glottis from beneath on nine 11- to 15-day-old lambs during artificially induced central apneas. RESULTS: Thirty-eight central apneas were induced. Complete glottic closure was present on 35/38 (92%) of these apneas. Complete glottic closure was always paralleled by thyroarytenoid muscle electromyogram (EMG) activity (35/38). In no instance was TA EMG recorded without complete glottic closure. Moreover, positive subglottic pressure and maintenance of lung volume above functional residual capacity were observed in 27/30 (90%) and 18/19 (95%), respectively, of these apneas where complete glottic closure was present. CONCLUSIONS: Complete glottic closure is present throughout most artificially induced central apneas in lambs. Complete glottic closure is paralleled by TA EMG in artificially induced central apneas. Thyroarytenoid muscle electromyographic activity is a reliable way to document complete glottic closure during apneas, especially in the presence of positive subglottic pressure. These observations suggest that complete glottic closure could be a physiologic mechanism aimed at maintaining higher lung volumes to improve gas exchange during central apneas.

Coordination between glottic adductor muscle and diaphragm EMG activity in fetal lambs in utero.

It has previously been reported that active glottic adduction is present during prolonged apneas but absent during periods of breathing movements in fetal lambs in utero. The present study was aimed at examining the precise coordination between fetal breathing movements [diaphragm electromyographic (EMG) activity (Di EMG)] and glottic adduction [thyroarytenoid muscle EMG activity (TA EMG)]. Electrodes for electroencephalogram, eye movements, TA EMG, and Di EMG and an arterial catheter were surgically implanted in fetal lambs 123-142 days postconception. Polygraphic recordings were performed without sedation while the ewe breathed room air (n = 11) or various gas mixtures (hypoxia, n = 5; hyperoxia, n = 4; hypercapnia, n = 5; hypercapnia+hyperoxia, n = 5). Tonic TA EMG was observed throughout >90% of apneas (>6 s) in both non-rapid-eye-movement and rapid-eye-movement sleep, and when Di EMG frequency decreased in rapid-eye-movement sleep. In all but two fetuses, TA EMG was immediately inhibited when Di EMG appeared. Altering blood gases did not modify these results. In conclusion, Di EMG and TA EMG are well coordinated in late gestation in fetal lambs, except in a few cases. These findings may have consequences for understanding the pathogenesis of mixed/obstructive apneas of prematurity.

Laryngeal and abdominal muscle electrical activity during periodic breathing in nonsedated lambs.

We recently reported that glottic closure was present throughout central apneas in awake lambs. The present study tested whether glottic closure was also observed during periodic breathing (PB). We attempted to induce PB in 21 nonsedated lambs on return from hypocapnic hypoxia to room air. Airflow and thyroarytenoid (a laryngeal constrictor, n = 16), cricothyroid (a laryngeal dilator, n = 10), and abdominal (n = 9) muscle electrical activity (EMG) were monitored continuously. PB was observed in 16 lambs, with apneic phases in 8 lambs. Thyroarytenoid muscle EMG was observed at the nadir of PB, either throughout apnea or with prolonged expiration during the lowest respiratory efforts. Phasic inspiratory cricothyroid muscle EMG and phasic expiratory abdominal EMG disappeared at the nadir of PB. Active glottic closure at the nadir of PB, without abdominal muscle contraction, could be a beneficial mechanism, preserving alveolar gas stores for continuing gas exchange during the apneic/hypopneic phase of PB. However, consequences of active glottic closure on ventilatory instability, either enhancing or reducing, are unknown.

Abolition of breathing rhythmicity in lambs by CO2 unloading in the first hours of life.

The mechanisms responsible for the maintenance of regular breathing after initiation of breathing at birth are still poorly understood. This study was designed to test the hypothesis that removing the chemical CO2 drive would abolish breathing rhythmicity in lambs in the first hours of life. A technique of graded CO2 removal through a veno-venous extracorporeal circuit was used in five unanesthetized lambs aged from 4 to 12 hours. In all lambs, CO2 unloading invariably resulted in sustained central apnea, after a decrease in Paco, of 6.9 +/- 5.7 Torr. We were unable to find a significant relationship between the decrease in PaCO2 and PaO2 (range 35-275 Torr) at onset of apnea. During apnea, the passage from behavioral quiet sleep to arousal or to active sleep was marked by transient and weak breathing movements. We conclude that the CO2 drive, but not the behavioral states, is a major factor for maintaining breathing rhythmicity in lambs in the first hours of life.

Influence of sleep states on laryngeal and abdominal muscle response to upper airway occlusion in lambs.

This study was aimed at describing abdominal and laryngeal muscle responses to upper airway occlusion (UAO) in early life and the effect of sleep states on these responses. Twelve nonsedated, 9-26-d-old lambs were studied. We simultaneously recorded 1) airflow (pneumotachograph + face mask); 2) sleep states (electrocorticogram and electrooculogram); 3) abdominal muscle (external obliquus) electromyogram (EMG); and 4) glottic constrictor (thyroarytenoid) and dilator (posterior cricoarytenoid and cricothyroid) muscle EMGs. The pneumotachograph was repeatedly occluded for 15-30 s in wakefulness and natural sleep. We analyzed 90 occlusions during wakefulness (11 lambs), 28 during non-rapid eye movement (nREM) sleep (six lambs), and 23 during rapid eye movement (REM) sleep (five lambs). A phasic expiratory external obliquus EMG was present during baseline and progressively increased throughout UAO in wakefulness and nREM sleep, but not in REM sleep. Phasic thyroarytenoid EMG progressively increased during inspiratory efforts throughout UAO in wakefulness and nREM sleep, paralleling the increase in glottic dilator (posterior cricoarytenoid and cricothyroid) EMG. In contrast, glottic muscle response to UAO in REM sleep was severely blunted or disorganized by frequent swallowing movements. We conclude that UAO triggers complex and coordinated laryngeal and abdominal muscle responses during wakefulness and nREM sleep in lambs; these responses are largely absent, however, in REM sleep. These unique results, together with the defective arousal response in REM sleep, suggest that vulnerability to airway occlusion could be increased during REM sleep in early life. Possible implications for understanding severe postnatal apneas are discussed.

Periodic breathing induced on demand in awake newborn lamb.

Spontaneous periodic breathing, although a common feature in fullterm and preterm human infants, is scarce in other newborn mammals. The aim of this study was to induce periodic breathing in lambs. Four 10-day-old and two <48-h-old awake lambs were instrumented with jugular catheters connected to an extracorporeal membrane lung aimed at controlling arterial PCO2 (PaCO2). Arterial PO2 (PaO2) was set and maintained at the desired level by changing inspired O2 fraction and providing O2 through a small catheter into the "apneic" lung. At a critical PaO2/PaCO2 combination, the four 10-day-old lambs exhibited periodic breathing that could be initiated, terminated, and reinitiated on demand. In the 2-day-old lambs with low chemoreceptor gain, periodic breathing was hardly seen, regardless of the trials done to find the critical PO2/PCO2 combination. We conclude that periodic breathing can be induced in lambs and depends on critical PaO2/PaCO2 combinations and maturity of the chemoreceptors.

Inferior pharyngeal constrictor electromyographic activity during permeability pulmonary edema in lambs.

Newborn mammals exhibit an active expiratory upper airway closure during the first hours of extrauterine life. We have recently shown that permeability pulmonary edema led to active expiratory glottic closure in awake newborn lambs while hypoxia (inspired O2 fraction 8%; 15 min) did not. In the present study, we tested the hypothesis that expiratory glottic closure was accompanied by an increase in pharyngeal constrictor muscle expiratory electromyographic (EMG) activity. We studied seven awake nonsedated lambs aged 8-20 days. Airflow (facial mask + pneumotachograph), blood gases (arterial catheter), and EMG activity of both the thyroarytenoid muscle (a glottic adductor) and the inferior pharyngeal constrictor muscle were recorded before and after intravenous injection of halothane (0.05 ml/kg) to induce a permeability pulmonary edema. A central apnea (duration 15 s to 5 min) with continuous thyroarytenoid and inferior pharyngeal constrictor activity was observed within seconds after halothane injection. One lamb died despite rescuing maneuvers. An expiratory phasic thyroarytenoid and inferior pharyngeal constrictor muscle activity with simultaneous zero airflow gradually took place and, by 30 min after halothane injection, was present at each expiration in the six remaining lambs. Expiratory glottic and pharyngeal constrictor muscle EMG activity was subsequently present during the whole study period (1.5-5 h), even after correction of the initial hypoxia. Permeability lung edema was present at postmortem examination in all seven lambs. We conclude that a permeability pulmonary edema induced by intravenous halothane in non-sedated lambs enhances both glottic and pharyngeal constrictor muscle expiratory EMG. We hypothesize that expiratory contraction of the inferior pharyngeal constrictor muscle could participate in the active expiratory upper airway closure; this, in turn, might improve alveolocapillary gas exchange by increasing the end-expiratory lung volume.

Prolonged active glottic closure after barbiturate-induced respiratory arrest in lambs.

We recently showed that the glottis is actively closed throughout post-hyperventilation, hypocapnic central apnea in lambs. The present study was designed to test whether the glottis is also closed in non-hypocapnic central apnea. Twenty-seven lambs aged 2 to 30 days were intravenously injected with 325 mg of sodium pentobarbital, so as to obtain breathing arrest. Airflow was recorded via a facial mask and pneumotachograph, along with the electromyographic activity (EMG) of the thyroarytenoid muscle (TA, a glottic adductor). With the onset of apnea, continuous TA EMG appeared in a few seconds and rose rapidly. Brief inspiratory gasps were observed in eight lambs, and TA EMG was abruptly inhibited for the exact duration of the gasps. The continuous TA EMG then disappeared after 115 to 230 sec. We conclude that the glottis is actively closed during fatal non-hypocapnic central apnea in lambs. Our data suggest that active glottic closure occurs with major depression of central inspiratory drive.

Postnatal maturation of peripheral chemoreceptor ventilatory response to O2 and CO2 in newborn lambs.

Although studies on lambs have shown that carotid body sensitivity to O2 is reset postnatally, it is still unknown whether O2 and CO2 peripheral chemoreflexes undergo parallel postnatal maturation. The present study was designed to analyze maturation of O2 and CO2 peripheral chemoreflexes in 10 lambs at < 24 h and at 12 days of age. We measured the ventilatory (VE) response to three tidal breaths of pure N2 or 13% CO2 in air. Overall, the N2 peripheral chemoreflex increased significantly with maturation [VE/end-tidal O2 (ml.min-1.kg-1.Torr-1) = 2.94 +/- 0.91 at < 24 h vs. 5.13 +/- 0.59 at 12 days, P < 0.05], whereas the CO2 peripheral chemoreflex did not change (VE/end-tidal CO2 = 7.04 +/- 0.98 at < 24 h vs. 7.75 +/- 1.07 at 12 days, not significant). We conclude that the CO2 peripheral chemoreflex does not change in awake lambs within the time frame studied, in contrast to a marked postnatal maturation of the O2 peripheral chemoreflex. The different time courses of O2 and CO2 peripheral chemoreflex maturation support the concept that carotid body sensitivities to O2 and CO2 do not depend on the same basic mechanisms.