Effects of moderate hyperbilirubinemia on nutritive swallowing and swallowing-breathing coordination in preterm lambs

Background: Hyperbilirubinemia (HB) occurs in 90% of preterm newborns. HB induces acute neurological disorders (somnolence, abnormal tone, feeding difficulties, auditory dysfunction) and alterations in respiratory control. These findings suggest brainstem neurotoxicity that could also affect swallowing centers. Objective: To test the hypothesis that HB impairs nutritive swallowing (NS) and swallowing-breathing coordination. Methods: Two groups of preterm lambs (born 14 days prior to term), namely control (n = 6) and HB (n = 5), were studied. On day 5 of life (D0), moderate HB (150-250 µmol/l) was induced during 17 h in the HB group. Swallowing was assessed via recording of pharyngeal pressure and respiration by respiratory inductance plethysmography and pulse oximetry. The effect of HB on NS was assessed during standardized bottle-feeding. A second recording was performed 48 h after recovery from HB (D3). Results: Swallows were less frequent (p = 0.003) and of smaller volume (p = 0.01) in HB lambs while swallowing frequency was decreased (p = 0.004). These differences disappeared after HB normalization. Swallowing-breathing coordination was impaired in HB lambs, with a decrease in percent time with NS burst-related apneas/hypopneas at D0 and D3. Simultaneously, HB lambs tended to experience more severe desaturations (<80%) during bottle-feeding. Finally, following bottle-feeding, the respiratory rate was significantly lower, along with an increased apnea duration in HB lambs. Conclusions: Swallowing and swallowing-breathing coordination are altered by acute moderate HB in preterm lambs. Decreased efficiency at bottle-feeding is accompanied by continuation of breathing during swallow bursts, which may promote lung aspiration

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

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

Effect of moderate hyperbilirubinemia on cardiorespiratory control in preterm lambs

L’hyperbilirubinémie (HB) se développe chez 90% des nouveau-nés prématurés. L’HB modérée peut induire des désordres neurologiques aigus. L'HB sévère a été liée à une augmentation des apnées-bradycardies du prématuré. L'objectif de cette étude est de tester notre hypothèse selon laquelle une HB modérée perturbe le contrôle cardiorespiratoire chez les nouveau-nés prématurés, via une accumulation et/ou une neurotoxicité de la bilirubine au niveau des centres de contrôle cardiorespiratoire. Méthodes : Deux groupes d'agneaux prématurés (14 jours avant terme), contrôle (n=6) et HB (HB, n=5) ont été étudiés. À 5 jours de vie (J0), une HB modérée (150-250 ?mol/L) a été induite par injection iv de bilirubine durant 17h chez les agneaux HB. Les effets de l’HB modérée sur la commande respiratoire de base, la variabilité du rythme cardiaque (VRC) et respiratoire ont été évalués durant des polysomnographies, à J0 et 72h après (J3), après normalisation de la bilirubinémie. L'effet de l’HB sur la réactivité cardiorespiratoire a été analysé à J0 et J3 durant i/ des chémoréflexes laryngés (CRL) induits par injection supra-glottique de HCI, ii/ des chémoréflexes pulmonaires (CRP) provoqués par injection iv de capsaïcine et iii/ une exposition à l’hypoxie. Les cerveaux ont été analysés en imagerie magnétique par résonance (IRM) et histopathologie afin de mettre en évidence les dépôts centraux de bilirubine et d'éventuelles anomalies neuroanatomiques. Résultats : À J0, l’HB modérée augmente le temps passé en apnée spontanée. Elle est responsable d'une co-activation sympatho-vagale avec augmentation de la VRC et d'une perturbation de la rythmogenèse respiratoire. Elle altère la réactivité du système de contrôle cardiorespiratoire, comme l’attestent la diminution de l’inhibition cardiorespiratoire liée aux CRL et aux CRP, ainsi que l’augmentation de la réponse cardiaque à l’hypoxie. Ces effets sont pour la plupart réversibles à J3. Les analyses IRM et histopathologiques n'ont révélé aucune différence majeure entre les 2 groupes. Conclusions : L’HB modérée perturbe le contrôle cardiorespiratoire chez les agneaux prématurés. Bien que cela n'ait pu être démontré dans cette thèse, ces anomalies fonctionnelles pourraient être liées à la neurotoxicité de la bilirubine au niveau des centres de contrôle cardiorespiratoire. L’HB, même modérée, apparait donc comme un facteur important à prendre en compte dans la pathogénie et le traitement des apnées du prématuré

Effect of moderate hyperbilirubinemia on cardiorespiratory control in preterm lambs

L’hyperbilirubinémie (HB) se développe chez 90% des nouveau-nés prématurés. L’HB modérée peut induire des désordres neurologiques aigus. L'HB sévère a été liée à une augmentation des apnées-bradycardies du prématuré. L'objectif de cette étude est de tester notre hypothèse selon laquelle une HB modérée perturbe le contrôle cardiorespiratoire chez les nouveau-nés prématurés, via une accumulation et/ou une neurotoxicité de la bilirubine au niveau des centres de contrôle cardiorespiratoire. Méthodes : Deux groupes d'agneaux prématurés (14 jours avant terme), contrôle (n=6) et HB (HB, n=5) ont été étudiés. À 5 jours de vie (J0), une HB modérée (150-250 ?mol/L) a été induite par injection iv de bilirubine durant 17h chez les agneaux HB. Les effets de l’HB modérée sur la commande respiratoire de base, la variabilité du rythme cardiaque (VRC) et respiratoire ont été évalués durant des polysomnographies, à J0 et 72h après (J3), après normalisation de la bilirubinémie. L'effet de l’HB sur la réactivité cardiorespiratoire a été analysé à J0 et J3 durant i/ des chémoréflexes laryngés (CRL) induits par injection supra-glottique de HCI, ii/ des chémoréflexes pulmonaires (CRP) provoqués par injection iv de capsaïcine et iii/ une exposition à l’hypoxie. Les cerveaux ont été analysés en imagerie magnétique par résonance (IRM) et histopathologie afin de mettre en évidence les dépôts centraux de bilirubine et d'éventuelles anomalies neuroanatomiques. Résultats : À J0, l’HB modérée augmente le temps passé en apnée spontanée. Elle est responsable d'une co-activation sympatho-vagale avec augmentation de la VRC et d'une perturbation de la rythmogenèse respiratoire. Elle altère la réactivité du système de contrôle cardiorespiratoire, comme l’attestent la diminution de l’inhibition cardiorespiratoire liée aux CRL et aux CRP, ainsi que l’augmentation de la réponse cardiaque à l’hypoxie. Ces effets sont pour la plupart réversibles à J3. Les analyses IRM et histopathologiques n'ont révélé aucune différence majeure entre les 2 groupes. Conclusions : L’HB modérée perturbe le contrôle cardiorespiratoire chez les agneaux prématurés. Bien que cela n'ait pu être démontré dans cette thèse, ces anomalies fonctionnelles pourraient être liées à la neurotoxicité de la bilirubine au niveau des centres de contrôle cardiorespiratoire. L’HB, même modérée, apparait donc comme un facteur important à prendre en compte dans la pathogénie et le traitement des apnées du prématuré

Non-invasive devices and methods for large animal monitoring using automated video processing

International audienceObjectives: It is now standard for polysomnographical equipment to include video recording, although this modality is generally underexploited, since there is no automated processing associated with the latter. In thepresent report, we investigated the set of features that can be automatically extracted from a video recording, in the context of monitoring of freely moving, non-sedated, newborn lambs. Material and methods: Our database contained seven lambs and a total of 11 recordings, using two different cameras allowing a top view and a side view. Using appropriate methodologies, we show that it is possible to estimate the lamb's movements, its posture (standing or lying) as well as its covered trajectory. Results: Results are discussed as a function of the camera and show that side view recording is well suited for accurate scoring of the lamb's posture, whereas trajectory is best estimated using the top view camera. On the other hand, both cameras provide qualitatively similar results for the estimation of movement of the animals. Conclusion: The data gained from automated video processing, as reported herein, may have multiple applications, especially for animal studies, but may also be extended to human sleep monitoring

Identification and expression of a factor of the DM family in the oyster Crassostrea gigas

International audienceThe Pacific oyster Crassostrea gigas is a successive not systematic protandric hermaphrodite. Searching for an ortholog to Dmrt1, a conserved sex determinism factor, we have identified the first complete cDNA of a DM factor in Lophotrochozoa which we have called Cg-DMl (Crassostrea gigas DMRT-like). It is 359aa long, with the DM domain common to all the family factors, and one DMA domain specific to members such as Dmrt4 and Dmrt5. Its gene presents one intron of 598 bp. Real time PCR and in situ hybridization have shown that Cg-DMl was expressed in both sexes, with a significantly higher expression in male than in female gonads at the end of the adult gametogenetic cycle and that a significant peak of expression was observed in spat between 1 and 2 months of age. These results suggest that Cg-DMl may be involved in the development of the gonad and may constitute preliminary clues for future work in order to better understand DM protein evolution

Molecular cloning and gene expression of Cg-Foxl2 during the development and the adult gametogenetic cycle in the oyster Crassostrea gigas

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Moderate Hyperbilirubinemia Alters Neonatal Cardiorespiratory Control and Induces Inflammation in the Nucleus Tractus Solitarius

International audienceHyperbilirubinemia (HB) occurs in 90% of preterm newborns. Moderate HB can induce acute neurological disorders while severe HB has been linked to a higher incidence of apneas of prematurity. The present study aimed to test the hypothesis that even moderate HB disrupts cardiorespiratory control in preterm lambs. Two groups of preterm lambs (born 14 days prior to term), namely control (n = 6) and HB (n = 5), were studied. At day 5 of life, moderate HB (150-250 μmol/L) was induced during 17 h in the HB group after which cardiorespiratory control as well as laryngeal and pulmonary chemoreflexes were assessed during baseline recordings and during hypoxia. Recordings were repeated 72 h after HB induction, just before euthanasia. In addition, neuropathological studies were performed to investigate for cerebral bilirubin deposition as well as for signs of glial reactivity in brainstem structures involved in cardiorespiratory control. Results revealed that sustained and moderate HB: (i) decreased baseline respiratory rate and increased the time spent in apnea; (ii) blunted the cardiorespiratory inhibition normally observed during both laryngeal and pulmonary chemoreflexes; and (iii) increased heart rate in response to acute hypoxia. These acute physiological changes were concurrent with an activation of Alzheimer type II astrocytes throughout the brain, including the brainstem. Concomitantly, bilirubin deposits were observed in the leptomeninges, but not in brain parenchyma. While most cardiorespiratory alterations returned to normal 72 h after HB normalization, the expression of glial fibrillary acid protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba1) was still increased within the nucleus tractus solitarius. In conclusion, moderate and sustained HB in preterm lambs induced cardiorespiratory alterations, the latter of which were associated with neurohistopathological changes. These changes are indicative of an inflammatory response in the brainstem neuroanatomical substrates involved in cardiorespiratory control