Estimation de la pression alvéolaire et de la compliance du système respiratoire en ventilation liquidienne totale

La ventilation liquidienne totale (VLT) est une méthode expérimentale de ventilation mécanique durant laquelle les poumons sont entièrement remplis d’un composé respirable de per uorocarbones (PFC) liquides. Le renouvellement d’un volume courant ltré, exempt de dioxyde de carbone, oxygéné et réchau é est e ectué par un ventilateur liquide dédié. La technologie de la VLT peut être utilisée pour les nouveau-nés en détresse respiratoire sévère, pour le lavage pulmonaire ou pour l’induction ultra rapide d’une hypothermie thérapeutique modérée. La surdistension alvéolaire est une cause importante de lésions pulmonaires dans le domaine de la ventilation mécanique. A n d’éviter ce traumatisme causé par la ventilation, un suivi précis de la pression alvéolaire et de la relation pression alvéolaire–volume pulmonaire doit être e ectué durant la VLT. La compliance du système respiratoire est une approximation linéaire de cette relation. En pratique, la ventilation est e ecutée de sorte à maximiser la compliance. Ceci permet d’avoir une ventilation e cace, à l’abri des risques de surdistension. L’objectif de ce projet est de développer des méthodes d’estimation précises de la pression alvéolaire et de la compliance a n de fournir des informations cruciales permettant au clinicien d’anticiper et d’éviter toute lésion pulmonaire en VLT. L’utilisation d’un liquide ayant une forte densité et de tubes exibles pour connecter le patient au ventilateur entraîne des intéractions uide-structure complexes qui sont inconnues des ventilateurs mécaniques conventionnels. Ces intéractions se décrivent par des résonances de basse fréquence se trouvant dans la bande passante des signaux respiratoires. Des méthodes sont ainsi proposées a n d’extraire précisément la pression alvéolaire à partir de mesures de pression contenant des résonances durant des pauses respiratoires courtes. Ces méthodes permettent aussi de caractériser les modes de résonance et d’estimer la compliance du système respiratoire. Les méthodes proposés sont analysées à l’aide de simulations de monte-carlo et d’une simulation de ventilation typique. Finalement, une des méthodes est utilisée pour e ectuer le post-traitement des données issues d’un protocole expérimental antérieur réalisé sur 6 agneaux nouveau-nés

Diagnosing hydrogen sulfide toxicosis with a silver/sulfide ion-selective electrode

The objective of this project was to develop a rapid, simple and inexpensive quantitative analysis to confirm hydrogen sulfide toxicosis in livestock based on acid extraction of sulfide in a wash-bottle unit and potentiometric determination with an ion-selective electrode (ISE). A silver/sulfide ISE and double-junction reference electrode coupled to a digital pH/mV meter with an automatic temperature compensation probe provided rapid and stable measurement of sulfide down to 0.02 ppm S[superscript]-2 using a liter-beaker calibration technique. The analysis was further facilitated by sealing standardized solutions and extracted unknown samples in serum bottles after flushing with nitrogen gas and storing at 4°C;The wash-bottle developed during the research provided excellent sulfide recoveries from aqueous samples (87 to 96%), but extraction from animal tissues was plagued by sample coagulation, foaming and poor to excellent percent recoveries. Whole and clotted blood were the worst samples for coagulation and foaming problems, compared to brain, lung, serum or plasma. Diluting the sample prior to extraction, and acidifying with dilute acids prevented coagulation. Foaming was combated with a mineral oil-poloxalene mixture (50:50 v/v), redesigning the wash-bottle, and reducing the nitrogen flow rate. Mean percentage of spike recovered were: blood, 7 to 43; blood clot, 13; serum, 58; plasma, 80; brain, 83 to 101; and lung, 76 to 102;Poor sulfide recovery and concentrating ability of the extraction unit prevented estimating endogenous blood sulfide concentrations ( 0.05) from endogenous levels due to the large variance in the resulting sulfide estimates. Specimens should be collected as soon as possible, with steps taken to preserve the sulfide content (refrigeration, flash freezing, or zinc precipitation), rapid delivery to the laboratory under preservation, and prompt analysis

Impact hémodynamique, suivi des volumes pulmonaires et inflammation en lien avec la ventilation liquidienne totale chez l’agneau nouveau-né

Introduction : La prise en charge respiratoire des patients nés extrêmement prématurés peut créer des dommages pulmonaires induits par la ventilation mécanique (VILI, Ventilator- Induced Lung Injury). Ces dommages contribuent au développement pathologique des poumons et à l’apparition de la maladie pulmonaire chronique du nouveau-né, aussi appelée dysplasie bronchopulmonaire (DBP). La ventilation liquidienne totale (VLT), qui a montré des avantages prometteurs dans la prise en charge d’une détresse respiratoire, pourrait prévenir le développement de la DBP en diminuant le VILI. Cependant, plusieurs zones d’ombre persistent avant de de pouvoir considérer son utilisation chez des modèles d’extrêmes prématurés. Projet 1 : Les données de la littérature sur la tolérance hémodynamique du nouveau-né soumis à une VLT varient selon le dispositif et l’algorithme de ventilation utilisés. L’impact du perfluorocarbone dense dans les poumons sur le remplissage ventriculaire a été très peu abordé dans la littérature. Avec le développement d’une technologie de VLT permettant de contrôler avec précision les volumes pulmonaires, une nouvelle étude s’imposait. Ainsi, dans un article publié dans PLOS-one (PMID 29377922), il a été montré que, chez un modèle d’agneau nouveau-né à terme avec déficit induit en surfactant, la VLT était bien tolérée et n’avait que des effets négligeables sur la fonction cardiaque, principalement lors de la phase d’inspiration. Projet 2 : Chez ces mêmes agneaux, un deuxième projet qui visait à évaluer la distribution du perfluorocarbone dans les poumons durant la transition de la ventilation gazeuse (VG) à la VLT a été mis en place. Il a été démontré, dans un article publié dans Frontiers in Physiology (PMID 30555353), que l’air est principalement évacué dans les dix premières minutes de ventilation. De plus, il a été montré que le volume courant (VT) était distribué de façon plus homogène qu’en VG, suggérant un meilleur rapport ventilation/perfusion. Projet 3 : Finalement, les modalités optimales de VLT en termes de VT, de fréquence respiratoire (FR) et leurs conséquences sur l’inflammation pulmonaire demeuraient, à ce jour, inconnu. De plus, très peu d’essais de retour en respiration spontanée après une VLT ont été décrits dans la littérature chez le modèle animal néonatal. Un projet chez l’agneau à terme sain a donc été mis en place afin de comparer l’influence des grands VT (20 ml/kg) avec celle des petits VT (10 ml/kg) sur l’expression des gènes impliqués dans l’inflammation et sur le retour en respiration spontanée. L’article a été publié dans Frontiers in Physiology (PMID 32625110). Il a ainsi été montré que l’utilisation de la VLT avec des VT plus élevés associés à des FR plus faibles avait un profil inflammatoire pulmonaire favorable en comparaison avec des VT plus faibles et des FR élevées. Aucune différence n’a été décelée dans les étapes du sevrage post-VLT. Le projet a aussi mis en évidence la possibilité de ramener en respiration spontanée les agneaux en moins de 4h suivant la VLT. Conclusion : Les résultats obtenus durant ces travaux de thèse ont grandement contribué à améliorer les connaissances en physiologie de la VLT chez l’agneau à terme, ce qui permet maintenant d’envisager des études chez des agneaux extrêmement prématurés et ultimement chez les extrêmes prématurés humains

Lung function and structure in Cystic Fibrosis infants one year after diagnosis by newborn screening.

Identifying early signs of lung disease reliably in asymptomatic infants with Cystic Fibrosis (CF) diagnosed by newborn screening (NBS) is a challenge. Very little is known about the origin and progression of lung disease in these infants hence there is uncertainty on best interventions to protect the lungs of these infants from functional and structural decline. This collaborative observational study aims to assess lung function and structure in CF NBS infants. Lung function tests (LFT) were performed in contemporaneous healthy controls and CF infants at 3 months and a year of age. In addition, CF infants underwent chest computed tomography (CT) at 1 year under general anaesthesia within 2 weeks of the LFTs. At a year, CF NBS infants had impaired lung function compared to contemporaneous healthy controls. However the percentage of CF NBS infants demonstrating what was considered abnormal lung function had reduced at a year of age compared to those with abnormal result at 3 months. Although some improvements were observed at 1- year LFTs, this was not universal using the different techniques. Some measurements improved, others remained stable and certainly none deteriorated. In terms of CT structural changes in CF NBS infants, fewer abnormalities were detected in our cohort compared to other reported studies and changes seen were mild. There was poor correlation between lung function and structure in this group of CF infants. To accurately detect CF infants with impaired lung function or structural abnormalities using important physiological and clinical determinants would play an important role in the management of these infants. This study could inform power calculation for future interventional studies using relevant clinical trial endpoints related to lung function and structure

Aerospace Medicine and Biology. an Annotated Bibliography. 1958-1961 Literature, Volumes VII-X, Part 2

Abstracts on aerospace medicine and biology - bibliography on environmental factors, safety and survival, personnel, pharmacology, toxicology, and life support system

Aerospace Medicine and Biology - A cumulative index to a continuing bibliography

Cumulative index for abstracts of NASA documents on aerospace medicine and biolog

An investigation into regional ventilation in infants and children; its distribution and determinants

Changing body position is commonly used in the management of individuals with respiratory diseases and those receiving mechanical ventilation, in order to optimise ventilation and oxygenation. In acute respiratory distress syndrome (ARDS), prone positioning is reported to improve oxygenation by recruiting collapsed dorsal lung regions, although this has not been confirmed in children. Ventilation distribution is well established in adults as being gravity dependent. Clinical practice in the paediatric population has been guided by the notion that all children, irrespective of the presence or absence of disease and age, consistently demonstrate the opposite ventilation distribution pattern to adults and this pattern is said to occur until the second decade of life. Studies in the paediatric population are limited to a few reported from the 1980's, on very heterogeneous populations. With advances in technology, new methods of examining regional ventilation, such as electrical impedance tomography (EIT), have become available. Recent neonatal studies using EIT have reported a dissimilar ventilation distribution to the conventional paediatric pattern. Despite a growing number of studies examining the effects of various interventions on ventilation distribution, very few exist in infants and children older than 6 months of age. Furthermore, differing methodologies and the manner in which ventilation distribution is described and analysed makes pooling the available data in the paediatric population extremely difficult. An understanding of how ventilation is distributed under normal conditions is imperative when examining the effects of different interventions and medical conditions on ventilation distribution. This thesis aimed to describe the effects of body position, head position, age, and respiratory muscle activity on ventilation distribution in children between six months and nine years of age under normal conditions, with respiratory disease, neuromuscular disease, and during mechanical ventilation. Furthermore, the effect on ventilation distribution of prone positioning in children with ARDS was evaluated. Regional ventilation distribution was measured using thoracic EIT and respiratory muscle activity was measured using surface electromyography (sEMG) using standardised methodology. Results of a series of sub-studies indicate that ventilation distribution is more complex and variable than previously thought, with no standard "paediatric pattern" of ventilation. Overall, greater ventilation occurred in the right and dorsal lungs, respectively, in different positons. Head position did not affect regional ventilation in the children studied. Age had a variable effect on ventilation distribution, with healthy children under 12 months of age more likely to follow the paediatric pattern, particularly in side lying positions; however the response was not uniform. The presence of mechanical ventilation, disease state and respiratory muscle activity did not affect ventilation distribution with these children also showing variable patterns of regional ventilation distribution. Data suggests that turning children with ARDS into the prone position does not result in recruitment of the dorsal lung regions, but rather more homogenous ventilation throughout the lungs. Furthermore, results suggest that children with greater ventilation inhomogeneity at baseline are more likely to respond positively (improvement in oxygenation index) to prone positioning. This research provides novel insights into ventilation distribution and respiratory muscle activity in infants and children older than six months of age under a number of different conditions. These results contribute to a better understanding of the factors influencing the distribution of regional ventilation and the mechanisms by which prone positioning in ARDS may improve oxygenation in this population. These findings have potentially important clinical implications, as well as providing baseline data for future clinical studies. Given the variability observed, these studies highlight the potential clinical utility of EIT to monitor different interventions and outcomes. An important strength of the studies presented in this thesis, is that they were performed in a standardised manner, using relatively homogenous individual populations and validated measures of describing ventilation distribution. This methodology could provide a template for future studies in the paediatric population, to allow for comparison between studies

The development and function of the nasopharynx and its role in the evolution of primate respiratory abilities

The nasopharynx is a centrally located region of the upper respiratory tract (URT) integral to several physiological functions. However, few have focused on this area within the context of human evolution. This study investigated osseous morphology, soft tissue histology, development, and evolutionary change of the nasopharynx. Multimodal analyses were performed: Analysis 1: This study tested hypotheses on the morphological relationships of the osseous nasopharyngeal boundaries with the splanchnocranium and basicranium among dry crania representing humans and non-human primates using 3D geometric morphometrics (3D-GM). Results showed that humans, the most orthognathic group, exhibited the widest nasopharynges. Over human development, the nasopharynx grows vertically taller and anteroposteriorly shorter while the path of the cartilaginous Eustachian tube (CET) grows longer and more vertically oriented. Timing of these growth changes coincide with changes in frequency of otitis media. Analysis 2: The nasopharynx was hypothesized to warm and humidify air only via its bony, non-contractile surfaces. Air conditioning capacity was assessed by presence of submucosal blood vessels, mucous cells, and serous cells on histological slides of nasopharyngeal surfaces. Results indicated that all of these microstructures were present on all nasopharyngeal surfaces, rather than being restricted to non-conctractile bony surfaces. Analysis 3: Ambient climate was hypothesized to influence URT growth. Two groups of adult male Macaca mulatta raised in Oregon (cold climate) and California (warm climate) outdoor colonies were used. CT imaging and 3D-GM were performed. Results revealed no shape differences but the Oregon individuals exhibited larger airway size and smaller body mass than the California individuals. Thus being raised in cold climates appears related to development of larger URT proportions relative to body size. Analysis 4: Nasopharyngeal morphology of fossil hominins, including Neanderthals and mid-Pleistocene Homo (MPH) from Europe and Africa, were reconstructed using 3D coordinate data and analyzed via 3D-GM. Neanderthals exhibited greater CET length than MPH and modern humans while the horizontal CET orientation of Neanderthals resembled the human infant condition. Results strongly suggest that Neanderthals possessed CET morphology and physiology distinct from modern humans, likely impacting susceptibility to middle ear disease and supporting species-level distinction