Le contrôle de la ventilation procède d’une interaction complexe entre des efférences centrales à destination des groupes musculaires ventilatoires et des afférences ventilatoires provenant de mécano et de chémorécepteurs. Cette commande de la ventilation s’adapte en permanence aux besoins ventilatoires. L’activation électrique du diaphragme (EAdi) informe sur la commande ventilatoire, la charge des muscles respiratoires, la synchronie patient-ventilateur et l’efficacité de la ventilation des patients de réanimation. L’utilisation inadaptée d’un mode deventilation spontanée avec une sur ou sous-assistance peut entrainer des dysfonctions diaphragmatiques, des lésions alvéolaires et des asynchronies. La première étude a permis de cibler l’assistance du mode NAVA en fonction de l’EAdi enregistrée lors d’un échec de test de sevrage. Nous avons observé une augmentation quotidienne de cette EAdi au cours du sevrage jusqu’à l’extubation. La deuxième étude a montré que cette augmentation n’est pas associée à une modification de l’efficacité neuro-ventilatoire lors du test de sevrage, possiblement en rapport avec l’inhibition d’une sédation résiduelle. La troisième étude a montré l’importance de l’inhibition de cette sédation résiduelle par midazolam sur l’EAdi et le volume courant au début du sevrage ainsi que la corrélation qui existe entre les deux. Une dernière étude a montré l’absence d’augmentation du volume courant sous NAVA chez des patients transplantés pulmonaires aux poumons dénervés sans réflexe de Herring Breuer par rapport à un groupe contrôle. Par ailleurs le volume courant sous NAVA était corrélé à la capacité pulmonaire totale. Ces études ont montré l’intérêt du monitorage l’EAdi dans le sevrage. / The control of breathing results from a complex interaction involving differentrespiratory centers, which feed signals to a central control mechanism that, in turn, provides outputto the effector muscles. Afferent inputs arising from chemo- and mechanoreceptors, related to thephysical status of the respiratory system and to the activation of the respiratory muscles, modulatepermanently the respiratory command to adapt ventilation to the needs. Diaphragm electricalactivation provides information about respiratory drive, respiratory muscle loading, patientventilatorsynchrony and efficiency of breathing in critically ill patients. The use of inappropriatelevel of assist during spontaneous breathing with over or under assist might be harmful withdiaphragmatic dysfunction, alveolar injury and asynchrony. The first study settled NAVA modeaccording to the EAdi recorded during a failed spontaneous breathing trial (SBT). An unexpecteddaily increase of EAdi has been found during SBT until extubation. The second study did not findany increase of the neuroventilatory efficiency during weaning, possibly because of residualsedation. A third study described the inhibition of residual sedation on EAdi and tidal volume at thebeginning of the weaning, and the correlation between them. The last study did not find anyincrease of tidal volume under NAVA after lung transplantation, with denervated lung withoutHerring Breuer reflex, compared to a control group. Moreover tidal volume under NAVA wascorrelated to total lung capacity. These studies highlight the interest of EAdi monitoring duringweaning.

Hintergrund Durch die Entwicklung neuer in vivo Bildgebungsmethoden, z.B. der Computertomographie (CT) und der Positronen-Emissions-Tomographie (PET), konnte in den letzten Jahren das Verständnis über die Pathophysiologie des akuten Lungenversagens (acute respiratory distress syndrome, ARDS) maßgeblich verbessert werden. So zeigten PET/CT-Messungen, dass beim ARDS pathophysiologische Veränderungen von Lungenbelüftung und -durchblutung zu einer Störung des Gasaustausches beitragen. Die deshalb erforderliche mechanische Beatmung kann allerdings zu einer weiteren Schädigung der Lunge führen (ventilator induced lung injury, VILI). Bisher konnten weder die exakten pathophysiologischen Mechanismen des ARDS noch der potentiell schädigende Einfluss der mechanischen Beatmung vollständig geklärt werden. Fragestellung In dieser Doktorarbeit wurden PET/CT-Bildgebungstechniken für die Quantifizierung der pulmonalen Belüftung, neutrophilischen Inflammation und Perfusion im experimentellen Modell des ARDS verwendet. Hierfür wurden zwei Substudien durchgeführt. Ziel der ersten Substudie war es, in einem tierexperimentellen Modell des ARDS den relativen Einfluss der beiden wesentlichen Mechanismen von VILI, das zyklische Öffnen und Schließen von Alveolen (Atelektrauma) und die alveoläre Überdehnung (Volutrauma), auf die pro-inflammatorische Antwort der Lunge zu untersuchen. Die zweite Substudie hatte das Ziel, die Anwendung von Fluoreszenz-markierten Mikrosphären für Messungen der pulmonalen Perfusionsverteilung in akut geschädigten Lungen zu validieren. Es sollte geprüft werden, ob ex vivo Messungen mittels Fluoreszenz-markierten Mikrosphären alternativ zu in vivo PET/CT-Messungen mittels Gallium-68 (68Ga)-markierten Mikrosphären im experimentellen Modell das ARDS herangezogen werden können. Material und Methoden Es wurden zwei Substudien in analgosedierten, intubierten und mechanisch beatmeten Schweinen durchgeführt. Die Induktion des ARDS erfolgte durch repetitives, bronchoalveoläres Lavagieren mit isotonischer Kochsalzlösung. In der ersten Substudie erfolgten Untersuchungen an 10 Tieren. Nach Rekrutierung beider Lungen wurde eine absteigende Titration des positiven, end-exspiratorischen Drucks (positive end-expiratory pressure, PEEP) durchgeführt. Es folgte eine randomisierte Zuordnung der Versuchstiere zu einer vierstündigen Beatmungstherapie der linken, VILI Lunge zur Induktion eines Atelektraumas oder Volutraumas. In beiden Versuchsgruppen wurde ein vergleichbares Tidalvolumen von 3 ml/kg Körpergewicht appliziert. Zur Induktion von Volutrauma wurde ein hoher PEEP gewählt (2 cmH2O oberhalb des Levels, an dem sich die dynamische Compliance während der PEEP-Titration um mehr als 5 % erhöht). Zur Induktion von Atelektrauma wurde ein niedriger PEEP appliziert (PEEP, bei dem eine mit Volutrauma vergleichbare Atemwegsdruckdifferenz (Differenz aus Spitzendruck und PEEP) auftritt). In der rechten Lunge, welche als Kontrolllunge diente, wurde ein kontinuierlicher, positiver Atemwegsdruck von 20 cmH2O aufrechterhalten. Der Gasaustausch, insbesondere die Eliminierung von Kohlenstoffdioxid, wurde extrakorporal unterstützt. Nach vierstündiger Beatmung der linken, VILI Lunge erfolgte die Bildgebung. Für die Quantifizierung von Ausmaß und regionaler Verteilung der pulmonalen Inflammation wurde 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) intravenös injiziert und die Aktivität mittels dynamischen PET/CT-Aufnahmen erfasst. Die Erfassung der Lungenperfusion erfolgte mittels intravenös injizierten, 68Ga-markierten Mikrosphären und statischen PET/CT-Aufnahmen. Anschließende CT-Aufnahmen während Atemmanövern am Ende der Inspiration, Exspiration und am mittleren Atemvolumen dienten der Bestimmung von Lungenbelüftung, zyklischer Überdehnung und Rekrutierung. In der zweiten Substudie wurde in 7 Schweinen die Perfusion der linken und rechten Lunge untersucht (n = 14 Lungen). Nach jeweils einstündiger mechanischer Beatmung mittels zweiphasigem, positivem Beatmungsdruck überlagert mit einem Anteil an Spontanatmung am Minutenvolumen von 0 % oder > 60 % wurden Fluoreszenzmarkierte und 68Ga-markierte Mikrosphären intravenös injiziert. Unmittelbar im Anschluss erfolgten PET/CT-Messungen der Verteilung der 68Ga-markierten Mikrosphären. Für die Analyse der Verteilung der Fluoreszenz-markierten Mikrosphären wurden die Lungen am Versuchsende entnommen, getrocknet, in Würfel gesägt und die emittierende Fluoreszenz sowie das Gewicht jedes Würfels gemessen. Die in vivo PET-Aktivitätsmessungen wurden auf die mittels CT bestimmte Lungenmasse normalisiert (QRM). Die QRM-Daten wurden auf die Auflösung der Fluoreszenzmessungen herunterskaliert (QRM,downscaled). Die Analyse der ex vivo Fluoreszenzmessungen erfolgte durch Normalisierung auf die Masse der Lungenwürfel (QFM,Mass), auf deren Volumen (QFM,Volume) und auf Würfelmasse und -volumen (QFM,Mass,Volume). Die Auflösung und die äußeren Konturen der Lungen wurden zwischen ex vivo und in vivo Messungen verglichen. Lineare Regressionen von Perfusion und axialer Verteilung jedes Lungenvolumenelementes dienten der Bestimmung von Perfusionsgradienten entlang der ventro-dorsalen und kranio-kaudalen Achse. Die Anstiege der Regressionsgeraden wurden zwischen den Messmethoden verglichen. Für jede Lunge wurde die globale und regionale Perfusionsheterogenität bestimmt und zwischen den Messmethoden verglichen. Ergebnisse In der ersten Substudie verdeutlichten PET/CT-Messungen, dass, trotz vergleichbarer Perfusion, Volutrauma im Vergleich zu Atelektrauma zu einer höheren spezifischen Aufnahme von 18F-FDG in den beatmeten, VILI Lungen führte. Dieser Effekt trat hauptsächlich in zentralen Lungenregionen auf. Weiterhin führte Volutrauma, aber nicht Atelektrauma, zu einer höheren spezifischen 18F-FDG-Aufnahme in den beatmeten, VILI Lungen im Vergleich zu den nicht-ventilierten Kontrolllungen. CT-Aufnahmen verdeutlichten, dass Atelektrauma einen höheren Anteil an nicht belüfteten Lungenkompartimenten und mehr zyklische Rekrutierung zur Folge hatte. Volutrauma bedingte hingegen höhere Anteile an überblähten und normal belüfteten Lungenarealen und mehr zyklische Überdehnung. Die Atemwegsdruckdifferenzen waren anfänglich zwischen den Gruppen vergleichbar, stiegen im Verlauf bei Atelektrauma, aber nicht bei Volutrauma, an. In der zweiten Substudie verdeutlichten sowohl ex vivo QFM,Volume-Messungen, als auch in vivo QRM-Messungen die Existenz von Perfusionsgradienten entlang der ventrodorsalen und kranio-kaudalen Achsen, trotzdem QFM-Messungen eine 21-fach geringere Auflösung aufwiesen und die erforderliche Lungenentnahme und -trocknung eine Lungendeformation bedingte. Beide Messverfahren zeigten stärkere Perfusionen dorsaler und kaudaler im Vergleich zu ventraler und kranialer Lungenareale. Im Vergleich zu QRM,downscaled-Messungen wiesen QRM-Messungen höhere globale Perfusionsheterogenitäten auf. Verglichen mit QRM,downscaled-Messungen wiesen sowohl QFM,Volume-Messungen, als auch QFM,Mass,Volume-Messungen vergleichbare regionale Perfusionsheterogenitäten auf. Schlussfolgerungen In der ersten Substudie führte Volutrauma im Vergleich zu Atelektrauma, trotz vergleichbarem Tidalvolumen, geringerer Atemwegsdruckdifferenz und vergleichbarer Perfusion, zu einer höheren pulmonalen Inflammation. Dies deutet darauf hin, dass in diesem Modell des ARDS die mit Volutrauma assoziierten hohen statischen Drücke im Vergleich zu dynamischen Einflüssen die schädlicheren Mechanismen von VILI sind. Die zweite Substudie verdeutlichte, dass ex vivo Messungen der Verteilung von Fluoreszenz-markierten Mikrosphären bei Volumennormalisierung, trotz geringerer Auflösung und auftretenden Lungendeformationen, vergleichbare Messergebnisse hinsichtlich der Existenz und des Ausmaßes von Lungengradienten mit in vivo PET/CTMessungen aufzeigen. Eine Anpassung der Auflösung der in vivo Perfusionsmessungen an die der ex vivo Messungen verringerte sowohl die globale, als auch die regionale Perfusionsheterogenität. Bei gleicher Auflösung zeigten ex vivo QFM,Volume-Messungen vergleichbare globale und regionale Perfusionsheterogenitäten wie in vivo Messungen. Die Studienergebnisse deuten darauf hin, dass für die Quantifizierung von pulmonalen Perfusionsgradienten ex vivo QFM,Volume-Messungen alternativ zu in vivo PET/CTMessungen durchgeführt werden können.

Introducción: El presente proyecto de intervención en salud se realizó en el asentamiento humano Pacífico Villa parte alta, ubicado en el distrito de Chorrillos, donde la prevalencia y mortalidad por enfermedades respiratorias en niños menores de 5 años es alta y representa un problema en salud. Objetivos: El proyecto tuvo el objetivo de mejorar el conocimiento de la población sobre la prevención de enfermedades respiratorias agudas en niños menores de 5 años. Para lograr esto se incidió en las principales 3 causas encontradas que eran los inadecuados hábitos de higiene en niños y cuidadores involucrados, la baja cobertura de vacunación en los niños menores de 5 años y la malnutrición en los niños que los predispone a padecer todo tipo de enfermedades. Metodología: Se siguió la metodología del marco lógico, se realizó en primer lugar una priorización de problemas y el análisis de involucrados, se esquematizó el árbol de problemas y árbol de objetivos, a continuación, se analizaron las alternativas de solución y se graficó la estructura analítica del proyecto, luego se realizó la matriz del marco lógico y finalmente se plantearon las actividades y tareas resumidas en la matriz de programación. Actividades: Se realizaron 2 actividades principales que consistieron en la realización de afiches y videos para presentar a la comunidad vía online debido a la coyuntura actual de la pandemia por Sars-CoV-2. Resultados: Los resultados del proyecto a corto plazo se midieron por encuestas de conocimiento respondidas por la comunidad, una antes de la intervención y otra después, siendo el logro final la mejora de conocimiento de la comunidad en materia de prevención de enfermedades respiratorias, reconocimiento de sus signos de alarma, importancia de la vacunación, alimentación saludable, métodos de higiene, lactancia materna, entre otros. / Introduction: This health intervention project was carried out in the Pacific Villa upper part human settlement, located in the district of Chorrillos, where the prevalence and mortality from respiratory diseases in children under 5 years of age is high and represents a health problem. Objectives: The project had the objective of improving the population’s knowledge about prevention of acute respiratory diseases in children under 5 years of age. To achieve this, the main 3 causes found were involved, which were inadequate hygiene habits in children and their caregivers, low vaccination coverage in children under 5 years of age and malnutrition in children that predisposes them to suffer all kinds of diseases. Methodology: The logical framework approach was followed, first a prioritization of problems and the analysis of those involved were carried out, the tree of problems and tree of objectives were outlined, then the solution alternatives were analyzed and the analytical structure of the project, then the logical framework matrix was made and finally the activities and tasks summarized in the programming matrix were proposed. Activities: Two main activities were carried out, which consisted of making posters and videos to present to the community online due to the current situation of the Sars-CoV-2 pandemic. Results: The results of the short-term project were measured by knowledge surveys answered by the community, one before the intervention and another after, the final achievement being the improvement of the community's knowledge in the prevention of respiratory diseases, recognition of its warning signs, the importance of vaccination, healthy eating, hygiene methods, breastfeeding, among others. / Tesis

<p> Virus-induced modulation of dendritic cell function is thought to be an effective mechanism for viral-immune evasion. The severe-acute respiratory syndrome coronavirus (SARS-CoV) has been shown to infected human myeloid dendritic cells (MDCs) and directly modulate the cellular cytokine production. The ability of other human coronaviruses to infect MDCs and impair cell immune function has not been assessed. </p> <p> This thesis describes the infection of human MDCs with coronavirus 229E, NL63, and OC43. 229E showed productive, but limited genomic replication, nucleocapsid protein synthesis and infectious progeny release in MDCs. 229E infection stimulated IFN-α, IL-6 and MCP-1 production in MDCs, but little to no IL-12, TNF-α, IL-8, IP-10, or RANTES . 229E-infected MDCs showed poor CD80 expression, down-regulated CD86 and HLA-DR expression and were poor stimulators of CD4+ T cell proliferation. In contrast to 229E, OC43 showed persistent and productive genomic replication, nucleocapsid protein synthesis and infectious progeny release in MDCs. OC43 infection stimulated IFN-α, IL-12, IP-10 and MCP-1 production in MDCs, but little to no TNF-α, IL-6, IL-8 or RANTES . The up-regulation of maturation molecules and CD4+ T cell stimulatory capacity in OC43-infected MDCs was donor cell-dependent. In contrast to 229E and OC43, NL63 infection of MDCs was non-productive, showing no viral genomic replication, protein production or infectious progeny release. NL63 infection stimulated strong cytokine (IFN-α, IL-12, TNF-β and IL-6) and chemokine (IL-8, IP-10, RANTES and MCP-1) responses in MDCs. NL63-infected MDCs showed up-regulated CD80, CD83, CD86 and HLA-DR expression and were efficient stimulators of CD4+ T cell proliferation. </p> <p> This study provides the first evidence that human coronaviruses other than SARSCo V can abrogate MDC immune effector function. It also provides the first side-by-side comparison of 229E, NL63 and OC43 and identifies the potential of 229E and OC43 to impair MDC cytokine production and T cell stimulation as a mechanism of immune response evasion. <p> / Thesis / Doctor of Philosophy (PhD)

40% of severe acute respiratory syndrome coronavirus two (SARS-CoV-2) severe cases develop acute kidney injury (AKI). Current treatment for renal complications limits financial and material resources available. To explore alternative treatments and accelerate research in case of future coronavirus outbreaks, a mouse model of coronavirus disease 2019-associated AKI (C19-AKI) would represent a critical biomedical research tool. The surrogate model of C19-AKI (SMC) developed consisted of angiotensin-converting enzyme two (ACE2) knockout (KO) mice receiving 400 ng/kg/min of angiotensin (Ang) II by osmotic minipump for eight days with a single injection of lipopolysaccharide (LPS; 10 mg/kg) on the seventh day of Ang II and euthanasia 24 hours after LPS. Similarly, to C19-AKI, the SMC exhibited albuminuria, elevated blood urea nitrogen, electrolyte imbalance, neutrophil infiltration, and upregulation of the G-coupled protein receptor (GPR)84 and pro-inflammatory and injury markers. GPR84 was found in bronchoalveolar lavage fluid neutrophils of coronavirus disease 2019 (COVID-19) patients, suggesting a potential implication of GPR84 in the disease. We hypothesised that GPR84 deletion or antagonism with GLPG-1205 could attenuate SMC’s indices of renal injury and inflammation. GLPG-1205 and GPR84 KO had no effects in the SMC model, as suggested by unchanged albuminuria, electrolytes, and markers expression. Interestingly, neutrophil infiltration was attenuated by GLPG-1205 only. The SMC is an interesting tool for therapeutic development for infections associated with renal injury, such as SARS-CoV-2. GPR84 role in the SMC needs to be further assessed.

No description available.

Introdução: A utilização da posição prona melhora significativamente a oxigenação de pacientes com síndrome do desconforto respiratório agudo (SDRA). Estudos prévios sugerem que o recrutamento das regiões pulmonares colapsadas e pobremente aeradas é um dos possíveis mecanismos responsáveis pela melhora da oxigenação, no entanto, os mesmos ainda não foram comprovados. Objetivos: Quantificar a distribuição regional da aeração e da perfusão pulmonar, em ambas as posições prona e supina, através da tomografia de impedância elétrica (TIE) e da tomografia computadorizada multislice (TC), correlacionando-as com as respectivas trocas gasosas. Métodos: Foram estudados 21 suínos, da raça Ladrasse anestesiados e em ventilação mecânica controlada. Os animais foram divididos em dois grupos, de acordo com o método de imagem. 13 animais foram estudados com a TIE (grupo TIE) e 8 animais foram estudados com a TC (grupo TC). Após a indução do modelo de lesão pulmonar (infusão intermitente de solução salina e ventilação lesiva por 3 horas), os animais foram submetidos a uma manobra de recrutamento alveolar máxima (MR) seguida por uma manobra de titulação da PEEP (MTP), realizada em passos decrementais de 2 em 2 cmH2O PEEP. Onze animais (7 no grupo TIE e 4 no grupo TC) foram randomizados para iniciar o estudo na posição supina, seguida de uma segunda MR e MTP na posição prona. Dez animais (6 no grupo TIE e 4 no grupo TC) receberam as manobras na ordem inversa. Para o estudo da perfusão foram adicionados mais sete animais (2 no grupo TIE e 5 no grupo TC) que foram submetidos à injeção rápida de solução salina hipertônica e/ou de contraste iodado respectivamente. Resultados: Não foram encontradas diferenças significativas na quantidade de tecido pulmonar colapsado e hiperdistendido, entre as posições estudadas em ambos os grupos TIE e TC (p= 0.06). Entretanto, as trocas gasosas foram consistentemente melhores durante a posição prona (p<0.05), com shunt pulmonar significativamente menor (<55%, p<0.001) para níveis equivalentes de PEEP entre ambas as posições. A análise da perfusão pulmonar evidenciou a presença de grande fluxo sanguíneo pulmonar (2x mais perfusão específica) nas áreas de colapso pulmonar durante a posição supina, assim como a ausência de maiores efeitos gravitacionais na distribuição da perfusão entre as posturas. Conclusão: A análise quantitativa da TIE e da TC evidenciou que, para a mesma quantidade de tecido pulmonar colapsado, a oxigenação arterial foi sempre mais comprometida durante a posição supina, com aumento significativo do shunt pulmonar e com uma região de colapso pulmonar mais perfundida, sugerindo que a posição prona melhora a oxigenação e a relação ventilação perfusão, mas não atenua os efeitos gravitacionais sobre o parênquima pulmonar, o que não confirma os possíveis efeitos protetores associados à posição prona / Introduction: Prone position has been shown to consistently improve oxygenation in patients with acute respiratory distress syndrome (ARDS). Previous studies suggested some improvement in lung recruitment or a better ventilation of poorly aerated areas as possible mechanisms for such oxygenation benefits. Objective: To quantify the regional distribution of aeration (collapse and hyperdistend lung tissue) and lung perfusion by Computer Tomography (CT) and electrical impedance tomography in supine and prone positions and to correlate them with pulmonary gas exchange. Methods: We studied 21 anesthetized Landrace pigs under controlled mechanical ventilation. These animals were divided in two groups: Thirteen (13) animals in the EIT group and eight (8) in the CT group. After lung injury (saline lavage + VILI during 3 hours), animals were recruited and submitted to two sequential PEEP trials, both consisting of decremental PEEP steps (2 cmH2O steps). Seven (n=7) animals in the EIT group and four (4) in the CT group were allocated to a PEEP trial under supine position, followed by a second PEEP trial in prone. Six (6) animals in the EIT group and four (4) in the CT group received PEEP trials in reverse order. Seven (7) additional animals were studied for lung perfusion distribution, by analyzing the first pass kinetics of hypertonic solution (2 animals - EIT group) and iodine contrast (5 animals - CT group). Results: No differences in the amount of collapsed and hyperdistended lung tissue were found between both postures (p= 0.12 vs. p = 0.41 respectively) in both the EIT and CT groups. However, the gas exchange was consistently better (p <0.05), with much lower (55% lower) pulmonary shunt during prone position (p=0.001), at equivalent PEEP levels in both groups. The perfusion studies confirmed a higher perfusion ( 2 times increment in specific perfusion) of the atelectatic lung tissue in supine position, without majors gravitational effects between both positions. Conclusions: The quantitative analysis of EIT and CT showed that for the same amount of collapsed lung tissue, the PaO2 was always lower in supine position, with higher pulmonary shunt and higher perfusion of the collapsed lung areas. We could not demonstrate any lung protective effect associated with prone positioning. Thus, these results suggest that prone position improves oxygenation and V/Q imbalances, but it does not attenuate the effects of gravity on the lung

No description available.

Introdução: A utilização da posição prona melhora significativamente a oxigenação de pacientes com síndrome do desconforto respiratório agudo (SDRA). Estudos prévios sugerem que o recrutamento das regiões pulmonares colapsadas e pobremente aeradas é um dos possíveis mecanismos responsáveis pela melhora da oxigenação, no entanto, os mesmos ainda não foram comprovados. Objetivos: Quantificar a distribuição regional da aeração e da perfusão pulmonar, em ambas as posições prona e supina, através da tomografia de impedância elétrica (TIE) e da tomografia computadorizada multislice (TC), correlacionando-as com as respectivas trocas gasosas. Métodos: Foram estudados 21 suínos, da raça Ladrasse anestesiados e em ventilação mecânica controlada. Os animais foram divididos em dois grupos, de acordo com o método de imagem. 13 animais foram estudados com a TIE (grupo TIE) e 8 animais foram estudados com a TC (grupo TC). Após a indução do modelo de lesão pulmonar (infusão intermitente de solução salina e ventilação lesiva por 3 horas), os animais foram submetidos a uma manobra de recrutamento alveolar máxima (MR) seguida por uma manobra de titulação da PEEP (MTP), realizada em passos decrementais de 2 em 2 cmH2O PEEP. Onze animais (7 no grupo TIE e 4 no grupo TC) foram randomizados para iniciar o estudo na posição supina, seguida de uma segunda MR e MTP na posição prona. Dez animais (6 no grupo TIE e 4 no grupo TC) receberam as manobras na ordem inversa. Para o estudo da perfusão foram adicionados mais sete animais (2 no grupo TIE e 5 no grupo TC) que foram submetidos à injeção rápida de solução salina hipertônica e/ou de contraste iodado respectivamente. Resultados: Não foram encontradas diferenças significativas na quantidade de tecido pulmonar colapsado e hiperdistendido, entre as posições estudadas em ambos os grupos TIE e TC (p= 0.06). Entretanto, as trocas gasosas foram consistentemente melhores durante a posição prona (p<0.05), com shunt pulmonar significativamente menor (<55%, p<0.001) para níveis equivalentes de PEEP entre ambas as posições. A análise da perfusão pulmonar evidenciou a presença de grande fluxo sanguíneo pulmonar (2x mais perfusão específica) nas áreas de colapso pulmonar durante a posição supina, assim como a ausência de maiores efeitos gravitacionais na distribuição da perfusão entre as posturas. Conclusão: A análise quantitativa da TIE e da TC evidenciou que, para a mesma quantidade de tecido pulmonar colapsado, a oxigenação arterial foi sempre mais comprometida durante a posição supina, com aumento significativo do shunt pulmonar e com uma região de colapso pulmonar mais perfundida, sugerindo que a posição prona melhora a oxigenação e a relação ventilação perfusão, mas não atenua os efeitos gravitacionais sobre o parênquima pulmonar, o que não confirma os possíveis efeitos protetores associados à posição prona / Introduction: Prone position has been shown to consistently improve oxygenation in patients with acute respiratory distress syndrome (ARDS). Previous studies suggested some improvement in lung recruitment or a better ventilation of poorly aerated areas as possible mechanisms for such oxygenation benefits. Objective: To quantify the regional distribution of aeration (collapse and hyperdistend lung tissue) and lung perfusion by Computer Tomography (CT) and electrical impedance tomography in supine and prone positions and to correlate them with pulmonary gas exchange. Methods: We studied 21 anesthetized Landrace pigs under controlled mechanical ventilation. These animals were divided in two groups: Thirteen (13) animals in the EIT group and eight (8) in the CT group. After lung injury (saline lavage + VILI during 3 hours), animals were recruited and submitted to two sequential PEEP trials, both consisting of decremental PEEP steps (2 cmH2O steps). Seven (n=7) animals in the EIT group and four (4) in the CT group were allocated to a PEEP trial under supine position, followed by a second PEEP trial in prone. Six (6) animals in the EIT group and four (4) in the CT group received PEEP trials in reverse order. Seven (7) additional animals were studied for lung perfusion distribution, by analyzing the first pass kinetics of hypertonic solution (2 animals - EIT group) and iodine contrast (5 animals - CT group). Results: No differences in the amount of collapsed and hyperdistended lung tissue were found between both postures (p= 0.12 vs. p = 0.41 respectively) in both the EIT and CT groups. However, the gas exchange was consistently better (p <0.05), with much lower (55% lower) pulmonary shunt during prone position (p=0.001), at equivalent PEEP levels in both groups. The perfusion studies confirmed a higher perfusion ( 2 times increment in specific perfusion) of the atelectatic lung tissue in supine position, without majors gravitational effects between both positions. Conclusions: The quantitative analysis of EIT and CT showed that for the same amount of collapsed lung tissue, the PaO2 was always lower in supine position, with higher pulmonary shunt and higher perfusion of the collapsed lung areas. We could not demonstrate any lung protective effect associated with prone positioning. Thus, these results suggest that prone position improves oxygenation and V/Q imbalances, but it does not attenuate the effects of gravity on the lung

Homeostase do O2 é essencial para a sobrevivência e desenvolvimento fisiológico dos organismos. A falta de O2 nos tecidos é um fator subjacente comum na morbidade e mortalidade de situações clínicas como na Síndrome do Desconforto Respiratório Agudo (ARDS). Na retomada da homeostase as células mielóides exercem suas funções especializadas nas áreas de hipóxia. A adaptação destas células nesta condição depende dos produtos do gene HIF-1<font face=\"Symbol\">&#945, fator de transcrição que responde às mudanças de O2. Neste trabalho caracterizamos os mecanismos celulares e moleculares operantes no estado de hipóxia em resposta à reação inflamatória aguda no pulmão induzida pela I/R ateria mesentérica em duas linhagens de camundongos geneticamente selecionadas para máxima (AIRmax) ou mínima (AIRmin) Resposta Inflamatória Aguda (AIR). Observamos uma alta reação inflamatória aguda em resposta a I/R. Altos níveis de expressão dos genes envolvidos em situações de hipóxia Hif-1<font face=\"Symbol\">&#945, Vhl e das citocinas Il-1<font face=\"Symbol\">&#946 e Il-6 mostraram-se relacionados com a alta AIR nos camundongos AIRmax. / Oxygen homeostasis is essential for survival and physiologic development of organisms. Lack of O2 in tissues is a common underlying factor in morbidity and mortality for numerous serious medical conditions such as the Acute Respiratory Distress Syndrome (ARDS). For homeostasis recovery the myeloid cells exert their functions in specialized areas of hypoxia. The adaptation of myeloid cells in low O2 tissue depends on the HIF-1<font face=\"Symbol\">&#945 gene products. Hif-1<font face=\"Symbol\">&#945 is a transcription factor that responds to O2 levels change. In this study we characterize, in two lines of mice selected for maximal (AIRmax) or minimal (AIRmin) Acute Inflammatory response (AIR), the cellular and molecular mechanisms operating in the hypoxia state during an acute inflammatory reaction in the lung parenchyma produced by mesenteric artery Ischemia. We observed an acute inflammatory reaction with high levels of Hif-1<font face=\"Symbol\">&#945 and Vhl genes expression involved in hypoxia conditions and IL-1<font face=\"Symbol\">&#946 and IL-6 genes showed related to high AIR in AIRmax mice.