Ovine model of congenital chest wall and spine deformity: From birth to 3 months follow-up.

Background: The evolution and treatment of lung alterations related to congenital spine and chest wall deformities (CWD) are poorly understood. Most animal models of CWD created postnatally were not evaluated for respiratory function. The goal of our study was to evaluate the effects of a CWD induced in utero on lung growth and function in an ovine model. Methods: A CWD was induced in utero at 70-75 days of gestation in 14 ovine fetuses by resection of the 7th and 8th left ribs. Each non-operated twin fetus was taken as control. Respiratory mechanics was studied postnatally in the first week and at 1, 2, and 3 months. Post-mortem respiratory mechanics and lung histomorphometry were also assessed at 3 months. Results: Eight out of 14 CWD lambs (57%) and 14 control lambs survived the postnatal period. One severe and five mild deformities were induced. At birth, inspiratory capacity (25 vs. 32 mL/kg in controls), and dynamic (1.4 vs. 1.8 mL/cmH2O/kg), and static (2.0 vs. 2.5 mL/cmH2O/kg) respiratory system compliances were decreased in CWD lambs. Apart from a slight decrease in inspiratory capacity at 1 month of life, no other differences were observed in respiratory mechanics measured in vivo thereafter. Postmortem measurements found a significant decrease in lung compliance-for each lung and for both lungs taken together-in CWD lambs. No differences in lung histology were detected at 3 months in CWD animals compared to controls. Conclusions: Our study is the first to assess the effects of a prenatally induced CWD on lung development and function from birth to 3 months in an ovine model. Our results show no significant differences in lung histomorphometry at 3 months in CWD lambs compared to controls. Resolution at 1 month of the alterations in respiratory mechanics present at birth may be related to the challenge in inducing severe deformities.

Total liquid ventilation in an ovine model of extreme prematurity: a randomized study.

BACKGROUND: This study aimed at comparing cardiorespiratory stability during total liquid ventilation (TLV)-prior to lung aeration-with conventional mechanical ventilation (CMV) in extremely preterm lambs during the first 6 h of life. METHODS: 23 lambs (11 females) were born by c-section at 118-120 days of gestational age (term = 147 days) to receive 6 h of TLV or CMV from birth. Lung samples were collected for RNA and histology analyses. RESULTS: The lambs under TLV had higher and more stable arterial oxygen saturation (p = 0.001) and cerebral tissue oxygenation (p = 0.02) than the lambs in the CMV group in the first 10 min of transition to extrauterine life. Although histological assessment of the lungs was similar between the groups, a significant upregulation of IL-1a, IL-6 and IL-8 RNA in the lungs was observed after TLV. CONCLUSIONS: Total liquid ventilation allowed for remarkably stable transition to extrauterine life in an extremely preterm lamb model. Refinement of our TLV prototype and ventilation algorithms is underway to address specific challenges in this population, such as minimizing tracheal deformation during the active expiration. IMPACT: Total liquid ventilation allows for remarkably stable transition to extrauterine life in an extremely preterm lamb model. Total liquid ventilation is systematically achievable over the first 6 h of life in the extremely premature lamb model. This study provides additional incentive to pursue further investigation of total liquid ventilation as a transition tool for the most extreme preterm neonates.

Effects of Nasal Respiratory Support on Laryngeal and Esophageal Reflexes in Preterm Lambs.

BACKGROUND: Significant cardiorespiratory events can be triggered in preterm infants as part of laryngeal chemoreflexes (LCRs) and esophageal reflexes (ERs). We previously showed that nasal continuous positive airway pressure (nCPAP) blunted the cardiorespiratory inhibition induced with LCRs. Therefore, we aimed to compare the effects of nCPAP and high-flow nasal cannulas (HFNC) on the cardiorespiratory events induced during LCRs and ERs. The hypothesis is that nCPAP but not HFNC decreases the cardiorespiratory inhibition observed during LCRs and ERs. METHODS: Eleven preterm lambs were instrumented to record respiration, ECG, oxygenation, and states of alertness. LCRs and ERs were induced during non-rapid eye movement sleep in a random order under these conditions: nCPAP 6 cmH2O, HFNC 7 L/min, high-flow nasal cannulas 7 L/min at a tracheal pressure of 6 cmH2O, and no respiratory support. RESULTS: nCPAP 6 cmH2O decreased the cardiorespiratory inhibition induced with LCRs, but not with ERs in preterm lambs. This blunting effect was less marked with HFNC 7 L/min, even when the tracheal pressure was maintained at 6 cmH2O. CONCLUSIONS: nCPAP might be a treatment for cardiorespiratory events related to LCRs in newborns, either in the context of laryngopharyngeal refluxes or swallowing immaturity. Our preclinical results merit to be confirmed through clinical studies. IMPACT: Laryngeal chemoreflexes can be responsible for significant cardiorespiratory inhibition in newborns, especially preterm. Nasal continuous positive airway pressure at 6 cmH2O significantly decreased this cardiorespiratory inhibition. High-flow nasal cannulas at 7 L/min had a lesser effect than nasal continuous positive airway pressure. Esophageal stimulation was responsible for a smaller cardiorespiratory inhibition, which was not significantly modified by nasal continuous positive airway pressure or high-flow nasal cannulas. Nasal continuous positive airway pressure should be tested for its beneficial effect on cardiorespiratory events related to laryngeal chemoreflexes in preterm newborns.

Hemodynamic impacts of apelin-13 in a neonatal lamb model of septic peritonitis.

BACKGROUND: Apelins are potential candidate therapeutic molecules for hemodynamic support. The objective of this study was to assess the hemodynamic impacts of apelin-13 in a neonatal lamb model of septic shock. METHODS: Lambs were randomized to receive apelin-13 or normal saline. Septic shock was induced by injecting a fecal slurry into the peritoneal cavity. Lambs underwent volume repletion (30 mL/kg over 1 h) followed by intravenous administration of 5 incremental doses (D) of apelin-13 (D1 = 0.039 to D5 = 19.5 µg/kg/h) or normal saline. RESULTS: Following fecal injection, mean arterial pressure (MAP) and cardiac index (CI) dropped in both groups (p < 0.05). The MAP decreased non-significantly from D1 to D5 (p = 0.12) in the saline group, while increasing significantly (p = 0.02) in the apelin group (-12 (-17; 12) vs. +15 (6; 23) % (p = 0.012)). Systemic vascular resistances were higher in the apelin-13 group at D5 compared to the saline group (4337 (3239, 5144) vs. 2532 (2286, 3966) mmHg/min/mL, respectively, p = 0.046). The CI increased non-significantly in the apelin-13 group. CONCLUSION: Apelin-13 increased MAP in a neonatal lamb septic shock model. IMPACT: Administration of apelin-13 stabilized hemodynamics during the progression of the sepsis induced in this neonatal lamb model. Systemic vascular resistances were higher in the apelin-13 group than in the placebo group. This suggests ontogenic differences in vascular response to apelin-13 and warrants further investigation. This study suggests that apelin-13 could eventually become a candidate for the treatment of neonatal septic shock.

Corrigendum: Safety of Bottle-Feeding Under Nasal Respiratory Support in Preterm Lambs With and Without Tachypnoea.

[This corrects the article DOI: 10.3389/fphys.2021.785086.].

Cardiorespiratory alterations in a newborn ovine model of systemic viral inflammation.

BACKGROUND: Respiratory viruses can be responsible for severe apneas and bradycardias in newborn infants. The link between systemic inflammation with viral sepsis and cardiorespiratory alterations remains poorly understood. We aimed to characterize these alterations by setting up a full-term newborn lamb model of systemic inflammation using polyinosinic:polycytidylic acid (Poly I:C). METHODS: Two 6-h polysomnographic recordings were carried out in eight lambs on two consecutive days, first after an IV saline injection, then after an IV injection of 300 µg/kg Poly I:C. RESULTS: Poly I:C injection decreased locomotor activity and increased NREM sleep. It also led to a biphasic increase in rectal temperature and heart rate. The latter was associated with an overall decrease in heart-rate variability, with no change in respiratory-rate variability. Lastly, brainstem inflammation was found in the areas of the cardiorespiratory control centers 6 h after Poly I:C injection. CONCLUSIONS: The alterations in heart-rate variability induced by Poly I:C injection may be, at least partly, of central origin. Meanwhile, the absence of alterations in respiratory-rate variability is intriguing and noteworthy. Although further studies are obviously needed, this might be a way to differentiate bacterial from viral sepsis in the neonatal period. IMPACT: Provides unique observations on the cardiorespiratory consequences of injecting Poly I:C in a full-term newborn lamb to mimic a systemic inflammation secondary to a viral sepsis. Poly I:C injection led to a biphasic increase in rectal temperature and heart rate associated with an overall decrease in heart-rate variability, with no change in respiratory-rate variability. Brainstem inflammation was found in the areas of the cardiorespiratory control centers.

Conventional vs high-frequency ventilation for weaning from total liquid ventilation in lambs.

OBJECTIVE: To compare conventional gas ventilation (GV) and high-frequency oscillatory ventilation (HFOV) for weaning from total liquid ventilation (TLV). METHODS: Sixteen lambs were anesthetized. After 1 h of TLV with perflubron (PFOB), they were assigned to either GV or HFOV for 2 h. Oxygen requirements, electrical impedance tomography and videofluoroscopic sequences, and respiratory system compliance were recorded. RESULTS: The lambs under GV needed less oxygen at 20 min following TLV (40 [25, 45] and 83 [63, 98]%, p = 0.001 under GV and HFOV, respectively). During weaning, tidal volume distribution was increased in the nondependent regions in the GV group compared to baseline (p = 0.046). Furthermore, residual PFOB was observed in the most dependent region. No air was detected by fluoroscopy in that region at the end of expiration in the GV group. CONCLUSION: GV offers a transient advantage over HFOV with regards to oxygenation for TLV weaning.

Respiratory activity of the cricopharyngeus muscle in the neonatal period.

While phasic electrical activity of the cricopharyngeus muscle (EAcp)-the main component of the upper esophageal sphincter-occurs with inspiration and forceful expiration in adults, no such data is available for newborns. In addition, the effect of nasal respiratory support commonly used in newborns is unknown. We aimed to describe the phasic respiratory EAcp and to assess the potential effect of nasal CPAP (nCPAP, 6 cmH2O) or high-flow nasal cannula (HFNC, 7 L/min) in newborn lambs during 6-h recordings. Phasic EAcp was present in 11/17 lambs, including in 32 % (25, 81) [(median (Q1, Q3)] of respiratory cycles in wakefulness, 40 % (27, 70) in NREM sleep, and 10 % (0, 23) in REM sleep. In addition, EAcp was observed only during post-inspiration and/or expiration. Nasal CPAP or HFNC assessed in 7 of the 17 lambs did not have any effect. We conclude that phasic respiratory EAcp occurs in post-inspiration and expiration in newborn lambs.

Nasal respiratory support and tachypnea and oral feeding in full-term newborn lambs.

Newborn infants with respiratory difficulties frequently require nasal respiratory support such as nasal continuous positive airway pressure (nCPAP) or high-flow nasal cannulae (HFNC). Oral feeding of these infants under nasal respiratory support remains controversial out of fear of aspiration and cardiorespiratory events. The main objective of this study was to evaluate the safety of oral feeding under different types of nasal respiratory support in newborn lambs without or with tachypnea. Eight lambs aged 4-5 days were instrumented to record sucking, swallowing, respiration, ECG, oxygen saturation, and arterial blood gases. Each lamb was given two bottles of 30 mL of milk with a pause of 30 s under videofluoroscopy in four conditions [no respiratory support, nCPAP 6 cmH2O, HFNC 7 L/min, HFNCCPAP (= HFNC 7 L/min + CPAP 6 cmH2O)] administered in random order. The study was conducted in random order over 2 days, with or without standardized tachypnea induced by thoracic compression with a blood pressure cuff. Generalized linear mixed models were used to compare the four nasal respiratory supports in terms of safety (cardiorespiratory events and aspiration), sucking-swallowing-breathing coordination, and efficacy of oral feeding. Results reveal that no nasal respiratory support impaired the safety of oral feeding. Most of the few laryngeal penetrations we observed occurred with HFNCCPAP. Nasal CPAP modified sucking-swallowing-breathing coordination, whereas the efficiency of oral feeding decreased under HFNCCPAP. Results were similar with or without tachypnea. In conclusion, oral feeding under nasal respiratory support is generally safe in a term lamb, even with tachypnea.NEW & NOTEWORTHY The practice of orally feeding newborns suffering from respiratory problems while on nCPAP or HFNC remains controversial for fear of triggering cardiorespiratory events or aspiration pneumonia, or aggravating chronic lung disease. The present results show that bottle-feeding is generally safe in full-term lambs under nasal respiratory support, both without and with tachypnea.

Safety of Bottle-Feeding Under Nasal Respiratory Support in Preterm Lambs With and Without Tachypnoea.

Aim: Convalescing preterm infants often require non-invasive respiratory support, such as nasal continuous positive airway pressure or high-flow nasal cannulas. One challenging milestone for preterm infants is achieving full oral feeding. Some teams fear nasal respiratory support might disrupt sucking-swallowing-breathing coordination and induce severe cardiorespiratory events. The main objective of this study was to assess the safety of oral feeding of preterm lambs on nasal respiratory support, with or without tachypnoea. Methods: Sucking, swallowing and breathing functions, as well as electrocardiogram, oxygen haemoglobin saturation, arterial blood gases and videofluoroscopic swallowing study were recorded in 15 preterm lambs during bottle-feeding. Four randomly ordered conditions were studied: control, nasal continuous positive airway pressure (6 cmH2O), high-flow nasal cannulas (7 L•min-1), and high-flow nasal cannulas at 7 L•min-1 at a tracheal pressure of 6 cmH2O. The recordings were repeated on days 7-8 and 13-14 to assess the effect of maturation. Results: None of the respiratory support impaired the safety or efficiency of oral feeding, even with tachypnoea. No respiratory support systematically impacted sucking-swallowing-breathing coordination, with or without tachypnoea. No effect of maturation was found. Conclusion: This translational physiology study, uniquely conducted in a relevant animal model of preterm infant with respiratory impairment, shows that nasal respiratory support does not impact the safety or efficiency of bottle-feeding or sucking-swallowing-breathing coordination. These results suggest that clinical studies on bottle-feeding in preterm infants under nasal continuous positive airway pressure and/or high-flow nasal cannulas can be safely undertaken.

Effects of upper airway obstruction or hypoxia on gastroesophageal reflux in newborn lambs.

BACKGROUND: Although it is commonly accepted that upper airway obstruction (UAO) increases gastroesophageal reflux (GER), the link is poorly understood and insufficiently documented. In addition, while hypoxia is often encountered in infants with UAO, its consequences on GER are virtually unknown. The two aims of the present study were to characterize the effects of (1) UAO and (2) hypoxia on GER. METHODS: Seventeen lambs underwent polysomnographic and esophageal impedance/pH-metry monitoring during UAO vs. a control condition (6 h, ten lambs) or 10% hypoxia vs. normoxic condition (3 h, seven other lambs). RESULTS: Moderate-to-severe UAO was maintained throughout monitoring (inspiratory tracheal pressure of -13 (-15, -12) cm H2O vs. -1 (-1, -1) cm H2O in control condition, p = 0.005). While the number of GERs increased with UAO (2 (1, 4) vs. 0 (0, 3) in the control condition, p = 0.03), the increase was less than anticipated and inconsistent among the lambs. Also, sustained 10% hypoxia did not alter the number of GERs (2 (1, 3) vs. 0 (0, 5) in the control condition, p = 0.9). CONCLUSIONS: The presence of an UAO for 6 h mildly increased the number of GERs, whereas hypoxia for 3 h had no significant effect. IMPACT: The effect of upper airway obstruction and hypoxia on gastroesophageal reflux is poorly documented in the neonatal period. A moderate-to-severe upper airway obstruction for 6 h results in a mild, inconsistent increase in the number of gastroesophageal refluxes. Overall, a hypoxia of 10% for 3 h had no significant impact on gastroesophageal reflux. The prescription of an antireflux medication in infants with upper airway obstruction must not be systematic but rely on objective signs of a pathologic gastroesophageal reflux.

Effects of water restriction on social behavior and 5-HT neurons density in the dorsal and median raphe nuclei in mice.

We explored here the hypothesis that temporary chronic water restriction in mice affects social behavior, via its action on the density of 5-HT neurons in dorsal and median raphe nuclei (DRN and MRN). For that, we submitted adult C57BL/6 J mice to mild and controlled temporary dehydration, i.e., 6 h of water access every 48 h for 15 days. We investigated their social behavior in a social interaction task known to allow free and reciprocal social contact. Results showed that temporary dehydration increases significantly time spent in social contact and social dominance. It also expands 5-HT neuron density within both DRN and MRN and the behavioral and neuronal plasticity were positively correlated. Our findings suggest that disturbance in 5-HT neurotransmission caused by temporary dehydration stress unbalances choice processes of animals in social context.

Cardiorespiratory Alterations in a Newborn Ovine Model of Systemic Inflammation Induced by Lipopolysaccharide Injection.

Although it is well known that neonatal sepsis can induce important alterations in cardiorespiratory control, their detailed early features and the mechanisms involved remain poorly understood. As a first step in resolving this issue, the main goal of this study was to characterize these alterations more extensively by setting up a full-term newborn lamb model of systemic inflammation using lipopolysaccharide (LPS) injection. Two 6-h polysomnographic recordings were performed on two consecutive days on eight full-term lambs: the first after an IV saline injection (control condition, CTRL); the second, after an IV injection of 2.5 µg/kg Escherichia coli LPS 0127:B8 (LPS condition). Rectal temperature, locomotor activity, state of alertness, arterial blood gases, respiratory frequency and heart rate, mean arterial blood pressure, apneas and cardiac decelerations, and heart-rate and respiratory-rate variability (HRV and RRV) were assessed. LPS injection decreased locomotor activity (p = 0.03) and active wakefulness (p = 0.01) compared to the CTRL. In addition, LPS injection led to a biphasic increase in rectal temperature (p = 0.01 at ∼30 and 180 min) and in respiratory frequency and heart rate (p = 0.0005 and 0.005, respectively), and to an increase in cardiac decelerations (p = 0.05). An overall decrease in HRV and RRV was also observed. Interestingly, the novel analysis of the representations of the horizontal and vertical visibility network yielded the most statistically significant alterations in HRV structure, suggesting its potential clinical importance for providing an earlier diagnosis of neonatal bacterial sepsis. A second goal was to assess whether the reflexivity of the autonomic nervous system was altered after LPS injection by studying the cardiorespiratory components of the laryngeal and pulmonary chemoreflexes. No difference was found. Lastly, preliminary results provide proof of principle that brainstem inflammation (increased IL-8 and TNF-α mRNA expression) can be shown 6 h after LPS injection. In conclusion, this full-term lamb model of systemic inflammation reproduces several important aspects of neonatal bacterial sepsis and paves the way for studies in preterm lambs aiming to assess both the effect of prematurity and the central neural mechanisms of cardiorespiratory control alterations observed during neonatal sepsis.

Influence of nasal CPAP on cardiorespiratory control in healthy neonate.

The present study aimed to further unravel the effects of nasal continuous positive airway pressure (nCPAP) on the cardiovascular and respiratory systems in the neonatal period. Six-hour polysomnographic recordings were first performed in seven healthy newborn lambs, aged 2-3 days, without and with nCPAP application at 6 cmH2O (nCPAP-6), in randomized order. The effects of nCPAP-6 on heart rate variability, respiratory rate variability, and cardiorespiratory interrelations were analyzed using a semiautomatic signal processing approach applied to ECG and respiration recordings. Thereafter, a cardiorespiratory mathematical model was adapted to the experimental conditions to gain further physiological interpretation and to simulate higher nCPAP levels (8 and 10 cmH2O). Results from the signal processing approach suggest that nCPAP-6 applied in newborns with healthy lungs: 1) increases heart rate and decreases the time and frequency domain indices of heart rate variability, especially those representing parasympathetic activity, while increasing the complexity of the RR-interval time series; 2) prolongs the respiratory cycle and expiration duration and decreases respiratory rate variability; and 3) slightly impairs cardiorespiratory interrelations. Model-based analysis revealed that nCPAP-6 increases the heart rate and decreases respiratory sinus arrhythmia amplitude, in association with a reduced parasympathetic efferent activity. These results were accentuated when simulating an increased CPAP level. Overall, our results provide a further understanding of the effects of nCPAP in neonates, in the absence of lung disease.NEW & NOTEWORTHY Application of nasal continuous positive airway pressure (CPAP) at 6 cmH2O, a level very frequently used in newborns, alters heart and respiratory rate variability, as well as cardiorespiratory interrelations in a full-term newborn model without lung disease. Moreover, whereas nasal CPAP at 6 cmH2O decreases parasympathetic efferent activity, there is no change in sympathetic efferent activity.

Influence of Moderate Hyperbilirubinemia on Cardiorespiratory Control in Preterm Lambs.

Hyperbilirubinemia (HB) is responsible for neonatal jaundice in 60% of term newborns and 90% of preterm infants. Neonatal HB can induce neurological damage (acute HB encephalopathy) and has been associated with persistent apneas. The objective of the present study was to investigate the immediate and delayed effects of moderate, clinically-relevant HB on cardiorespiratory control in preterm lambs. Two groups of five preterm lambs, namely control and HB, were studied. At day five of life, moderate HB (150-250 µmol/L) was induced and maintained during 17 h in the HB group while control lambs received a placebo solution. Six hours after HB onset, 7-h polysomnographic recordings with electrocardiogram (ECG) and respiratory (RESP) signals were performed to assess the immediate effects of HB on heart rate variability (HRV), respiratory rate variability (RRV), and cardiorespiratory interrelations. Identical recordings were repeated 72 h after HB induction to examine the delayed effects of HB on HRV, RRV and cardiorespiratory interrelations. Our results demonstrate a higher HRV and vagal activity immediately after induction of moderate HB. Meanwhile, a decrease in respiratory rate with an increase in both long- and short-term RRV was also noted, as well as a higher amplitude of the respiratory sinus arrhythmia and cardiorespiratory coupling. Seventy-two hours later, the alterations in HRV, RRV, and cardiorespiratory interrelations were attenuated, although a number of them were still present, suggesting a lasting influence of HB on the basal control of the cardiorespiratory system. Our results pave the way for studies in human preterms to assess the relevance of monitoring HRV, RRV, and cardiorespiratory interrelations to detect the acute neurological effects of HB and consequently adapt the treatment of neonatal jaundice.

Mechanisms Associated with Type 2 Diabetes as a Risk Factor for Alzheimer-Related Pathology.

Current evidence suggests dementia and pathology in Alzheimer's Disease (AD) are both dependent and independent of amyloid processing and can be induced by multiple 'hits' on vital neuronal functions. Type 2 diabetes (T2D) poses the most important risk factor for developing AD after ageing and dysfunctional IR/PI3K/Akt signalling is a major contributor in both diseases. We developed a model of T2D, coupling subdiabetogenic doses of streptozotocin (STZ) with a human junk food (HJF) diet to more closely mimic the human condition. Over 35 weeks, this induced classic signs of T2D (hyperglycemia and insulin dysfunction) and a modest, but stable deficit in spatial recognition memory, with very little long-term modification of proteins in or associated with IR/PI3K/Akt signalling in CA1 of the hippocampus. Intracerebroventricular infusion of soluble amyloid beta 42 (Aß42) to mimic the early preclinical rise in Aß alone induced a more severe, but short-lasting deficits in memory and deregulation of proteins. Infusion of Aß on the T2D phenotype exacerbated and prolonged the memory deficits over approximately 4 months, and induced more severe aberrant regulation of proteins associated with autophagy, inflammation and glucose uptake from the periphery. A mild form of environmental enrichment transiently rescued memory deficits and could reverse the regulation of some, but not all protein changes. Together, these data identify mechanisms by which T2D could create a modest dysfunctional neuronal milieu via multiple and parallel inputs that permits the development of pathological events identified in AD and memory deficits when Aß levels are transiently effective in the brain.

A new ovine model of spine and chest wall deformity at birth with alteration of respiratory system mechanics and lung development: a feasibility study.

PURPOSE: To develop an animal model of spine and chest wall deformity (CWD) at birth and to evaluate its effects on respiratory system mechanics and lung development. METHODS: A spine and CWD was created in utero between 70 and 75 days of gestation in six ovine fetuses by resection of the seventh and eighth left ribs. Two days after birth, respiratory system mechanics was assessed in anesthetized lambs using the flexiVent apparatus, followed by postmortem measurement of lung mechanics as well as histological lung analysis. RESULTS: A range of severity of CWD was found (Cobb angle from 0° to 48°) with a mean decrease in compliance of 47% and in inspiratory capacity of 39% compared to control lambs. Proof-of-concept histological analysis in one lamb showed marked lung hypoplasia. CONCLUSION: Our ovine model represents a pilot proof-of-concept study evaluating the impact of a spine and CWD present at birth on lung respiratory mechanics and development. This study lays down the groundwork for future studies evaluating the impact of these deformities on lung development and potential treatments. These slides can be retrieved under Electronic Supplementary Material.

Assessment of tobacco smoke effects on neonatal cardiorespiratory control using a semi-automated processing approach.

A semi-automated processing approach was developed to assess the effects of early postnatal environmental tobacco smoke (ETS) on the cardiorespiratory control of newborn lambs. The system consists of several steps beginning with artifact rejection, followed by the selection of stationary segments, and ending with feature extraction. This approach was used in six lambs exposed to 20 cigarettes/day for the first 15 days of life, while another six control lambs were exposed to room air. On postnatal day 16, electrocardiograph and respiratory signals were obtained from a 6-h polysomnographic recording. The effects of postnatal ETS exposure on heart rate variability, respiratory rate variability, and cardiorespiratory interrelations were explored. The unique results suggest that early postnatal ETS exposure increases respiratory rate variability and decreases the coupling between cardiac and respiratory systems. Potentially harmful consequences in early life include unstable breathing and decreased adaptability of cardiorespiratory function, particularly during early life challenges, such as prematurity or viral infection. Graphical abstract ᅟ.

Implication of regional brain serotonergic neurons in dorsal and median Raphé nuclei in adaptation to water lacking in Gerbillus tarabuli.

The objective of this work was to investigate the implication of serotonin (5-HT) produced in the dorsal and medial raphé nuclei (DRN and MRN) in water homeostasis in desert animal Gerbillus tarabuli. For that, we measured the density of 5-HT immunolabeled neurons in hydrated and dehydrated animals (over 1 and six months). In this work, 5-HT positive neurons showed some change in shape and colour intensity in dehydrated gerbils comparing with hydrated gerbils. Furthermore a differential increase of 5-HT neurons density was observed in DRN subregions and in MRN following 1 and 6 months of dehydration. This study suggested that neurons in DRN and MRN contain 5-HT in various amounts, thus allowing an adapted response to hydration status. These neurons could mediate one of the adaptation mechanisms of this animal to its desert biotope.

Nasal high-frequency oscillatory ventilation inhibits gastroesophageal reflux in the neonatal period.

Nasal high-frequency oscillatory ventilation (nHFOV) in neonates is increasingly considered due to enhanced alveolar ventilation, absence of patient-ventilator asynchrony and lessened ventilator-induced lung injury. Although any type of non-invasive respiratory support can lead to gastric distension via esophageal air passage and thus promote gastroesophageal refluxes (GERs), we have shown that nasal continuous positive airway pressure (CPAP; 6 cmH2O) and intermittent positive pressure ventilation (15/4 cmH2O) conversely inhibit GERs in lambs. The current objective was to test the hypothesis that nHFOV also inhibits GERs compared to spontaneous ventilation without respiratory support. Eight lambs underwent five hours of polysomnographic and esophageal multichannel intraluminal impedance pHmetry recordings to assess GERs and air passage into the esophagus, with and without nHFOV (mean airway pressure = 8 cmH2O, oscillation frequency = 8 Hz, amplitude ≈ 20 cmH2O and I:E = 1:2). Results revealed that GERs were decreased with nHFOV (p = .03), despite an increase in gas-containing swallows (p = .01). In conclusion, similarly to nasal CPAP and intermittent positive pressure ventilation, nHFOV inhibits GERs in newborn lambs.