Nathalie Samson

Mechanisms of active laryngeal closure during noninvasive intermittent positive pressure ventilation in nonsedated lambs

The present study stems from our recent demonstration (Moreau-Bussiere F, Samson N, St-Hilaire M, Reix P, Lafond JR, Nsegbe E, Praud JP. J Appl Physiol 102: 2149-2157, 2007) that a progressive increase in nasal intermittent positive pressure ventilation (nIPPV) leads to active glottal closure in nonsedated, newborn lambs. The aim of the study was to determine whether the mechanisms involved in this glottal narrowing during nIPPV originate from upper airway receptors and/or from bronchopulmonary receptors. Two groups of newborn lambs were chronically instrumented for polysomnographic recording: the first group of five lambs underwent a two-step bilateral thoracic vagotomy using video-assisted thoracoscopic surgery (bilateral vagotomy group), while the second group, composed of six lambs, underwent chronic laryngotracheal separation (isolated upper airway group). A few days later, polysomnographic recordings were performed to assess glottal muscle electromyography during step increases in nIPPV (volume control mode). Results show that active glottal narrowing does not develop when nIPPV is applied on the upper airways only, and that this narrowing is prevented by bilateral vagotomy when nIPPV is applied on intact airways. In conclusion, active glottal narrowing in response to increasing nIPPV originates from bronchopulmonary receptors.

Radio telemetry devices to monitor breathing in non-sedated animals

Radio telemetry equipment has significantly improved over the last 10-15 years and is increasingly being used in research for monitoring a variety of physiological parameters in non-sedated animals. The aim of this review is to provide an update on the current state of development of radio telemetry for recording respiration. Our literature review found only rare reports of respiratory studies via radio telemetry. Much of this article will hence report our experience with our custom-built radio telemetry devices designed for recording respiratory signals, together with numerous other physiological signals in lambs. Our current radio telemetry system allows to record 24 simultaneous signals 24h/day for several days. To our knowledge, this is the highest number of physiological signals, which can be recorded wirelessly. Our devices have been invaluable for studying respiration in our ovine models of preterm birth, reflux laryngitis, postnatal exposure to cigarette smoke, respiratory syncytial virus infection and nasal ventilation, all of which are relevant to neonatal respiratory problems.

Effects of postnatal smoke exposure on laryngeal chemoreflexes in newborn lambs.

Laryngeal chemoreflexes (LCR), which are elicited by the contact of liquids such as gastric refluxate with laryngeal mucosa, may trigger some cases of sudden infant death syndrome. Indeed, while LCR in mature mammals consist of protective responses, previous animal data have shown that LCR in immature newborns can include laryngospasm, apnea, bradycardia, and desaturation. The present study was aimed at testing the hypothesis that postnatal exposure to cigarette smoke is responsible for enhancing cardiorespiratory inhibition observed with LCR. Eight lambs were exposed to cigarette smoke (20 cigarettes/day) over 16 days and compared with seven control lambs. Urinary cotinine/creatinine ratio was measured at a level relevant to previously published levels in infants. On days 15 and 16, 0.5 ml of HCl (pH 2), milk, distilled water, or saline was injected onto the larynx via a chronic supraglottal catheter during sleep. Results showed that exposure to cigarette smoke enhanced respiratory inhibition (P < 0.05) and tended to enhance cardiac inhibition and decrease swallowing and arousal during LCR (P < 0.1). Overall, these results were observed independently of the state of alertness and the experimental solution tested. In conclusion, 16-day postnatal exposure to cigarette smoke increases cardiorespiratory inhibition and decreases protective mechanisms during LCR in nonsedated full-term lambs.

Absence of inspiratory laryngeal constrictor muscle activity during nasal neurally adjusted ventilatory assist in newborn lambs

In nonsedated newborn lambs, nasal pressure support ventilation (nPSV) can lead to an active glottal closure in early inspiration, which can limit lung ventilation and divert air into the digestive system, with potentially deleterious consequences. During volume control ventilation (nVC), glottal closure is delayed to the end of inspiration, suggesting that it is reflexly linked to the maximum value of inspiratory pressure. Accordingly, the aim of the present study was to test whether inspiratory glottal closure develops at the end of inspiration during nasal neurally adjusted ventilatory assist (nNAVA), an increasingly used ventilatory mode where maximal pressure is also reached at the end of inspiration. Polysomnographic recordings were performed in eight nonsedated, chronically instrumented lambs, which were ventilated with progressively increasing levels of nPSV and nNAVA in random order. States of alertness, diaphragm, and glottal muscle electrical activity, tracheal pressure, Spo(2), tracheal Pet(CO(2)), and respiratory inductive plethysmography were continuously recorded. Although phasic inspiratory glottal constrictor electrical activity appeared during nPSV in 5 of 8 lambs, it was never observed at any nNAVA level in any lamb, even at maximal achievable nNAVA levels. In addition, a decrease in Pco(2) was neither necessary nor sufficient for the development of inspiratory glottal constrictor activity. In conclusion, nNAVA does not induce active inspiratory glottal closure, in contrast to nPSV and nVC. We hypothesize that this absence of inspiratory activity is related to the more physiological airway pressurization during nNAVA, which tightly follows diaphragm electrical activity throughout inspiration.

Effects of simulated reflux laryngitis on laryngeal chemoreflexes in newborn lambs

It has been suggested that reflux laryngitis (RL) is involved in apneas-bradycardias of the newborn. The aim of the present study was to develop a unique RL model in newborn lambs to test the hypothesis that RL enhances the cardiorespiratory components of the laryngeal chemoreflexes (LCR) in the neonatal period. Gastric juice surrogate (2 ml of normal saline solution with HCl pH 2 + pepsin 300 U/ml) (RL group, n = 6) or normal saline (control group, n = 6) was repeatedly injected onto the posterior aspect of the larynx, 3 times a day for 6 consecutive days, via a retrograde catheter introduced into the cervical esophagus. Lambs instilled with gastric juice surrogate presented clinical signs of RL, as well as moderate laryngitis on histological observation. Laryngeal chemoreflexes were thereafter induced during sleep by injection of 0.5 ml of HCl (pH 2), ewes milk, distilled water or saline into the laryngeal vestibule via a chronic, transcutaneous supraglottal catheter. Overall, RL led to a significantly greater respiratory inhibition compared with the control group during LCR, including longer apnea duration (P = 0.01), lower minimal respiratory rate (P = 0.002), and a more prominent decrease in arterial hemoglobin saturation (SpO(2)) (P = 0.03). No effects were observed on cardiac variables. In conclusion, 1) our unique neonatal ovine model presents clinical and histological characteristics of RL; and 2) the presence of RL in newborn lambs increases the respiratory inhibition observed with LCR, at times leading to severe apneas and desaturations.

Laryngeal Muscle Activity during Nasal High-Frequency Oscillatory Ventilation in Nonsedated Newborn Lambs

Background: We have previously shown that nasal pressure support ventilation (nPSV) can lead to an active inspiratory laryngeal narrowing in lambs. This, in turn, can limit lung ventilation and divert air into the digestive system, with potentially deleterious consequences. On the other hand, nasal high-frequency oscillatory ventilation (nHFOV) is particularly attractive in newborns, especially since, unlike nPSV, it does not require synchronization with the patients inspiratory efforts. Objectives: The main aim of the present study was to test the hypothesis that glottal constrictor muscle activity (EMG) does not develop during nHFOV. A secondary objective was to study laryngeal EMG during nHFOV-induced central apneas. Methods: Polysomnographic recordings were performed in 7 nonsedated lambs which were ventilated with increasing levels of nPSV and nHFOV at both 4 and 8 Hz, in random order. States of alertness, diaphragm and glottal muscle EMG, SpO2, and respiratory movements were continuously recorded. Results: While phasic inspiratory glottal constrictor EMG appeared with increasing nPSV levels in 6 out of 7 lambs, it was never observed with nHFOV. In addition, nHFOV at 4 Hz dramatically inhibited central respiratory drive in 4/7 lambs, with 64-100% of recording time spent in central apnea in 3 lambs. No glottal constrictor EMG was observed during these central apneas. Conclusion: nHFOV does not induce glottal constrictor muscle EMG in nonsedated newborn lambs, in contrast to nPSV. This may be an additional advantage of nHFOV relative to nPSV.

Effects of nasal continuous positive-airway pressure on nutritive swallowing in lambs

Current knowledge suggests that, to be successful, oral feeding in preterm infants should be initiated as soon as possible, often at an age where immature respiration still requires ventilatory support in the form of nasal continuous positive airway pressure (nCPAP). While some neonatologist teams claim great success with initiation of oral feeding in immature infants with nCPAP, others strictly wait for this ventilatory support to be no longer necessary before any attempt at oral feeding, fearing laryngeal penetration and tracheal aspiration. Therefore, the aim of the present study was to provide a first assessment of the effect of various levels of nCPAP on bottle-feeding in a neonatal ovine model, including feeding safety, feeding efficiency, and nutritive swallowing-breathing coordination. Eight lambs born at term were surgically instrumented 48 h after birth to collect recordings of electrical activity of laryngeal constrictor muscle, electrocardiography, and arterial blood gases. Two days after surgery, lambs were bottle-fed under five randomized nCPAP conditions, including without any nCPAP or nasal mask and nCPAP of 0, 4, 7, and 10 cmH(2)O. Results revealed that application of nCPAP in the full-term lamb had no deleterious effect on feeding safety and efficiency or on nutritive swallowing-breathing coordination. The present study provides a first and unique insight on the effect of nCPAP on oral feeding, demonstrating its safety in newborn lambs born at term. These results open the way for further research in preterm lambs to better mimic the problems encountered in neonatology.

Cricothyroid muscle electrical activity during respiration and apneas in lambs

Respiratory function of the cricothyroid muscle (CT) is virtually unknown in the neonatal period. This study was aimed at assessing CT electrical activity (EMG) during respiration and central apneas in non-sedated lambs. Seven full-term and four preterm lambs were instrumented for polysomnographic recording, including EMG of the diaphragm, thyroarytenoid (TA, a glottal constrictor), posterior cricoarytenoid (PCA, the primary glottal dilator) and CT. Phasic CT EMG was usually observed during inspiration and late expiration, whereas phasic TA EMG was observed during early expiration. While TA EMG virtually disappeared in REM sleep, both inspiratory and expiratory CT EMG increased. Overall, while CT EMG was not frequently observed during central apneas in either full-term (10% of apneas, but never simultaneously with TA EMG) or preterm lambs (30% of apneas), it was associated with decreased lung volume and subglottal pressure when present alone or with PCA EMG. Our results concur with the assumption that CT behaves as a laryngeal dilator in the neonatal period.

Laryngeal Stimulation by an Acid Solution in the Pre-term Lamb

In a mature organism, the contact between various liquids and the laryngeal mucosa triggers lower airway protective responses (cough, swallowing, arousal). These laryngeal chemoreflexes (LCR) are essential for preventing aspiration. In contrast, previous studies showed that LCR are responsible for apnea and bradycardia in the neonatal mammal. Consequently, LCR, especially when triggered by acid gastrolaryngeal reflux, are deemed responsible for some apneas of prematurity and many life-threatening events of infancy and, probably, for some cases of sudden infant death syndrome. Recently, we have revisited LCR in full-term lambs during quiet sleep. Our results showed that the LCR triggered by HCl (pH 2), mimicking the acid component of an acid gastro-oesophageal reflux, were consistently like the mature LCR reported in adult mammals, without significant apneas and bradycardias (St-Hilaire 2005). These results prompted us to question whether premature birth alters LCR. Results show that LCR triggered in pre-term lambs by both saline and HCl are much more marked and clinically relevant than the ones observed in full-term lambs. Indeed, life-threatening responses to HCl, including repetitive apneas for more than 90 seconds, severe desaturation and bradycardia, were observed in 2 lambs at postnatal day 7 (D7). In addition, LCR were significantly blunted at D14. In conclusion, HCl can trigger potentially dangerous LCR in pre-term lambs at D7, suggesting that LCR in response to acid gastrolaryngeal refluxes are likely involved in some apnea/bradycardia/desaturation in pre-term infants, before they reach a post-conceptional age equivalent to full gestation.

Effects of caffeine and/or nasal CPAP treatment on laryngeal chemoreflexes in preterm lambs

Current knowledge suggests that laryngeal chemoreflexes (LCR) are involved in the occurrence of certain neonatal apneas/bradycardias, especially in the preterm newborn. While caffeine and/or nasal continuous positive airway pressure (nCPAP) are the most frequent options used for treating apneas in preterm newborns, their effects on LCR-related apneas/bradycardias are virtually unknown. The aim of the present study was to test the hypothesis that caffeine and/or nCPAP decreases LCR-related cardiorespiratory inhibition in a preterm ovine model. Seven preterm lambs were born vaginally on gestational day 133 (normal gestation: 147 days) after intramuscular injections of betamethasone and mifepristone. Five days after birth, a chronic surgical instrumentation was performed to record states of alertness, electrocardiogram, systemic arterial pressure, and electromyographic activity of a laryngeal constrictor muscle, as well as to insert a transcutaneous supraglottal catheter. LCR were induced in quiet sleep under four conditions: 1) control (without caffeine or nCPAP); 2) nCPAP (5 cmH2O, without caffeine); 3) caffeine (10 mg/kg infused intravenously for 30 min, without nCPAP); and 4) nCPAP + caffeine. Our results showed that nCPAP consistently blunted LCR-related cardiorespiratory inhibition vs. control condition, contrary to caffeine whose overall effect was nonsignificant. In addition, nCPAP condition was characterized by a more consistent and rapid arousal after HCl injection. No significant differences were observed between all tested conditions with regard to swallowing and cough. It is concluded that nCPAP should be further assessed for its usefulness in treating neonatal apneas linked to LCR.