Orientador: José Roberto Fioretto / Resumo: A Síndrome do Desconforto Respiratório Agudo (SDRA) cursa com alta morbi-mortalidade apesar dos avanços no entendimento de sua fisiopatologia e tratamento. A terapia ventilatória baseia-se na proteção pulmonar, sendo a ventilação oscilatória de alta frequência (VOAF) uma opção de método protetor. A posição prona (PP) é terapia adjuvante que possibilita homogeneização da distribuição do volume corrente (VC) e promove recrutamento alveolar. O objetivo do estudo foi investigar o efeito da posição prona associada à VOAF e ventilação mecânica convencional (VMC) protetora sobre a oxigenação, inflamação, dano oxidativo e histologia pulmonares, comparando-a à posição supina em ambos os modos ventilatórios. Foram instrumentados 75 coelhos com traqueostomia e acessos vasculares. A lesão pulmonar aguda (LPA) foi induzida por lavagem traqueal de salina aquecida (30mL/Kg, 38°C). Os animais foram então aleatorizados em cinco grupos (n=15): 1) GC (Controle): animais sadios em VMC protetora basal; 2) GVMS: animais com LPA em VMC protetora e posição supina; 3) GVMP: animais com LPA em VMC protetora e posição prona; 4) GVAFS: animais com LPA em VOAF e posição supina; 5) GVAFP: animais com LPA em VOAF e posição prona. Após, foram submetidos a quatro horas de VMC protetora (modo pressão regulada-volume controlado, PEEP 10 cmH2O, VC 6mL/kg, Ti 0,5s, FR 40 rpm e FiO2 1) ou VOAF (MAP 15 mmHg, FR 10Hz, amplitude 22 e FiO2 1). O nível de significância foi de 5%. Após a indução, os grupos apresentaram... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Acute Respiratory Distress Syndrome (ARDS) presents with high morbidity and mortality despite advances in the understanding of its pathophysiology and treatment. Ventilatory therapy is based on the intention of injuring less, with high frequency oscillatory ventilation (HFOV) being a protective method option. Prone position (PP) is an adjuvant therapy that enables homogenization of volume tidal (VT) distribution and promotes alveolar recruitment. The aim of this study was to investigate the effects of prone position associated with HFOV and protective conventional mechanical ventilation (CMV) on oxygenation and lung inflammation, oxidative damage and histology, comparing it with the supine position in both ventilatory modes. Seventy five rabbits were submitted to tracheostomy and vascular accesses. ALI was induced by tracheal infusion of heated saline (30mL/kg, 38° C). The subjects were then ramdomized in five groups (n=15): 1) CG (Control): healthy animals in basal protective CMV; 2) MVSG: animals with ALI in protective CMV and supine position; 3) MVPG animals with ALI in protective CMV and prone position; 4) HFSG: animals with ALI in HFOV and supine position; 5) HFPG: animals with ALI in HFOV and prone position. After that, they were submitted to four hours of protective VMC (PRV mode, PEEP 10 cmH2O, VC 6ml/kg, Ti 0,5s, FR=40 rpm and FiO2 1) or HFOV (MAP 15 mmHg, FR 10 Hz, amplitude 22 and FiO2 1). The level of significance was 5%. After induction, the groups presented simi... (Complete abstract click electronic access below) / Doutor

Submitted by Rafaelle Batistella Pires (rafaelle.pires@gmail.com) on 2018-03-07T15:41:30Z No. of bitstreams: 1 Tese Rafaelle Batistella Pires.pdf: 2978722 bytes, checksum: f79b8076fd69934911d1a338cd131aa3 (MD5) / Approved for entry into archive by Luciana Pizzani null (luciana@btu.unesp.br) on 2018-03-08T20:07:06Z (GMT) No. of bitstreams: 1 pires_rb_dr_bot.pdf: 2978722 bytes, checksum: f79b8076fd69934911d1a338cd131aa3 (MD5) / Made available in DSpace on 2018-03-08T20:07:06Z (GMT). No. of bitstreams: 1 pires_rb_dr_bot.pdf: 2978722 bytes, checksum: f79b8076fd69934911d1a338cd131aa3 (MD5) Previous issue date: 2018-02-20 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A Síndrome do Desconforto Respiratório Agudo (SDRA) cursa com alta morbi-mortalidade apesar dos avanços no entendimento de sua fisiopatologia e tratamento. A terapia ventilatória baseia-se na proteção pulmonar, sendo a ventilação oscilatória de alta frequência (VOAF) uma opção de método protetor. A posição prona (PP) é terapia adjuvante que possibilita homogeneização da distribuição do volume corrente (VC) e promove recrutamento alveolar. O objetivo do estudo foi investigar o efeito da posição prona associada à VOAF e ventilação mecânica convencional (VMC) protetora sobre a oxigenação, inflamação, dano oxidativo e histologia pulmonares, comparando-a à posição supina em ambos os modos ventilatórios. Foram instrumentados 75 coelhos com traqueostomia e acessos vasculares. A lesão pulmonar aguda (LPA) foi induzida por lavagem traqueal de salina aquecida (30mL/Kg, 38°C). Os animais foram então aleatorizados em cinco grupos (n=15): 1) GC (Controle): animais sadios em VMC protetora basal; 2) GVMS: animais com LPA em VMC protetora e posição supina; 3) GVMP: animais com LPA em VMC protetora e posição prona; 4) GVAFS: animais com LPA em VOAF e posição supina; 5) GVAFP: animais com LPA em VOAF e posição prona. Após, foram submetidos a quatro horas de VMC protetora (modo pressão regulada-volume controlado, PEEP 10 cmH2O, VC 6mL/kg, Ti 0,5s, FR 40 rpm e FiO2 1) ou VOAF (MAP 15 mmHg, FR 10Hz, amplitude 22 e FiO2 1). O nível de significância foi de 5%. Após a indução, os grupos apresentaram comportamentos semelhantes, com diminuição da relação PaO2/FiO2 e da complacência pulmonar, e aumento do índice de oxigenação (IO) e da pressão média de via aérea (p > 0,05). Ao final do experimento, houve aumento da PaO2/FiO2 nos grupos VOAF comparado aos grupos em VMC (p < 0,05). Houve queda do IO para os grupos em VOAF comparados ao GVMS (p < 0,05), porém o GVMP não diferiu deles (p > 0,05). Não houve diferença estatística quanto à contagem de células polimorfonucleares no lavado broncoalveolar (BAL) nos grupos com LPA. Não houve diferença estatística entre os grupos com lesão para a medida de TNF-alfa no plasma e para sua expressão gênica em tecido pulmonar. Entretanto, a medida de TNF-alfa no lavado broncoalveolar (BAL) e no tecido pulmonar no grupo GVMP foi menor, assemelhando-se ao controle (p > 0,05). Não houve diferença no dano oxidativo avaliado no tecido pulmonar entre os grupos (p > 0,05) e, também, na comparação entre regiões ventral e dorsal dos pulmões. O escore de lesão histológica foi menor nos grupos em VOAF, efeito potencializado no grupo em prona quando comparado aos grupos em VMC (GC = GVAFP < GVMS = GVMP), sem diferença na regionalização pulmonar. Concluimos que, em modelo de LPA por lavagem alveolar com salina aquecida em coelhos: a VOAF melhora a oxigenação quando comparados à VMC; na VMC, a PP atenua a lesão inflamatória avaliada pela medida de TNF-alfa no BAL e tecido pulmonar; os modos ventilatórios e as posições não modificam o grau de estresse oxidativo quando avaliados pelo método de malondialdeído; a VOAF melhora o escore histopatológico de lesão pulmonar, independemente da posição, mas a associação de VOAF e PP atenua a lesão histopatológica quando comparada com a VMC protetora, seja em posição prona ou supina. / Acute Respiratory Distress Syndrome (ARDS) presents with high morbidity and mortality despite advances in the understanding of its pathophysiology and treatment. Ventilatory therapy is based on the intention of injuring less, with high frequency oscillatory ventilation (HFOV) being a protective method option. Prone position (PP) is an adjuvant therapy that enables homogenization of volume tidal (VT) distribution and promotes alveolar recruitment. The aim of this study was to investigate the effects of prone position associated with HFOV and protective conventional mechanical ventilation (CMV) on oxygenation and lung inflammation, oxidative damage and histology, comparing it with the supine position in both ventilatory modes. Seventy five rabbits were submitted to tracheostomy and vascular accesses. ALI was induced by tracheal infusion of heated saline (30mL/kg, 38° C). The subjects were then ramdomized in five groups (n=15): 1) CG (Control): healthy animals in basal protective CMV; 2) MVSG: animals with ALI in protective CMV and supine position; 3) MVPG animals with ALI in protective CMV and prone position; 4) HFSG: animals with ALI in HFOV and supine position; 5) HFPG: animals with ALI in HFOV and prone position. After that, they were submitted to four hours of protective VMC (PRV mode, PEEP 10 cmH2O, VC 6ml/kg, Ti 0,5s, FR=40 rpm and FiO2 1) or HFOV (MAP 15 mmHg, FR 10 Hz, amplitude 22 and FiO2 1). The level of significance was 5%. After induction, the groups presented similar behaviors, with a decrease in the PaO2/FiO2 ratio and lung compliance, and an increase in oxygenation index (OI) and mean airway pressure (p > 0.05). At the end of experimental time, PaO2/FiO2 increased in the HFOV groups compared to the CMV groups (p < 0.05). There was a decrease in OI for HFOV groups compared to MVSG (p < 0.05), but MVPG did not differ from them (p > 0.05). There was no statistically significant difference in polymorphonuclear cell counts in bronchoalveolar lavage (BAL) in the groups with ALI. There was no difference between ALI groups regarding the TNF-alfa dosage in plasma and its gene expression in lung tissue. However, TNF-alpha measurement in BAL and in lung tissue was smaller, resembling control (p > 0.05). There was no difference in the oxidative damage assessed in the lung tissue between the groups (p > 0.05), nor between the lung regions. The histological damage score was lower in the HFOV groups, potentiated effect in the prone group when compared to the CMV groups (CG = HFPG < MVSG = MVPG), no difference in pulmonary regionalization. We conclude that, in the model of ALI induced by alveolar lavage with heated saline in rabbits: HFOV improves oxygenation if compared to CMV; PP in CMV attenuates lung inflammation, evaluated by TNF-alfa dosage in BAL and in lung tissue; ventilatory modes and positions don’t modify the oxidative stress whan evaluated by malondialdehyde method; HFOV improves histopathological lung lesion score, regardless of position, but HFOV and prone position association attenuates histopathological injury compared to protective CMV, either in the prone or supine positions. / FAPESP: 2010/06242-8

The main purpose was describe the issue of shooting success rate at high altitude (1 500 - 3 000m a. s. l.). Shooting success rate of elite racers was evaluated using analysation of results from individual races at high altitude in the period 1990/1991 - 2013/2014. High altitude had no statistical effect (p<0,05) on shooting success rate of women and men biathletes in the comparision with lowland but it had more negative effect to women shooting success rate than men shooting success rate. Ten national level biathletes were tested in three tests in lowland, four tests at high altitude and five tests in lowland after the return from high altitude. The test included rest shooting in the prone and standing positions and load shooting in both positions which took part of three kilometers running. Twelve days training camp at high altitude did not improve shooting success rate, shooting velocity and running time in the determinated heart rate. Rest shooting and shooting in the prone position did not change statistically during the whole testing period. At high altitude critical days were registered in load shooting in standing position (6th day, p<0,05) and average running time (9th day, p<0,05). Rifle manipulation and shooting are automate motions which are not influenced by high altitude. Most...

The main purpose was describe the issue of shooting success rate at high altitude (1 500 - 3 000m a. s. l.). Shooting success rate of elite racers was evaluated using analysation of results from individual races at high altitude in the period 1990/1991 - 2013/2014. High altitude had no statistical effect (p<0,05) on shooting success rate of women and men biathletes in the comparision with lowland but it had more negative effect to women shooting success rate than men shooting success rate. Ten national level biathletes were tested in three tests in lowland, four tests at high altitude and five tests in lowland after the return from high altitude. The test included rest shooting in the prone and standing positions and load shooting in both positions which took part of three kilometers running. Twelve days training camp at high altitude did not improve shooting success rate, shooting velocity and running time in the determinated heart rate. Rest shooting and shooting in the prone position did not change statistically during the whole testing period. At high altitude critical days were registered in load shooting in standing position (6th day, p<0,05) and average running time (9th day, p<0,05). Rifle manipulation and shooting are automate motions which are not influenced by high altitude. Most...

Le syndrome de détresse respiratoire aiguë (SDRA) est caractérisé par des lésions alvéolairesdiffuses qui résultent d’une lésion de la membrane alvéolo-capillaire entrainant entre autresune réaction inflammatoire intense et une perte massive et hétérogène du volume pulmonaireaéré. La tomographie par émission de positons (TEP) et la tomographie par impédanceélectrique (TIE) sont deux techniques d’imagerie fonctionnelle permettant l’étude noninvasive, quantitative et régionale du poumon.Ce travail présente le résultat d’études expérimentales conduites dans le SDRA. Tout d’abord,nous avons comparé positivement la TIE à la TEP pour la mesure de la ventilation pulmonaireet du volume aéré. Nous avons ensuite décrit et validé une technique robuste d’obtention duvolume aéré et de la ventilation spécifique en TEP sans prélèvement invasif. Enfin, nousavons étudié en TEP l’influence de la pression expiratoire positive (PEP) et du décubitusventral (DV) sur la répartition de la ventilation, de la perfusion et de l’inflammationpulmonaires. Les poumons agressés par l’acide chlorhydrique inhalé ont une inflammationsignificativement plus élevée que le groupe contrôle. Aucune différence significatived’inflammation n’a été trouvée entre les groupes expérimentaux malgré des modificationsimportantes de la répartition de la ventilation et de la perfusion régionales lors de la mise enDV. Ces études donc ont permis le développement d’un modèle porcin stable d’agressionpulmonaire aiguë et la validation de techniques d’imagerie permettant l’étude non invasive deparamètres physiologiques importants pouvant aider au réglage de la ventilation mécanique aucours du SDRA. / Acute respiratory distress syndrome (ARDS) is characterized by diffuse alveolar damage andresulting from an increased permeability of the alveolar-capillary membrane. Of notice, thereis an intense lung inflammation. Positron emission tomography (PET) and electricalimpedance tomography (EIT) allow noninvasive assessment of pulmonary ventilation,perfusion and inflammation. We use these techniques to decipher the impairments ofventilation and inflammation throughout the lungs in an experimental model of acute lunginjury by hydrochloric acid inhalation in pigs.In a first study, we compared EIT to PET in quantifying pulmonary aerated volume andventilation, using PET as a gold standard. We found that lung ventilation and volume wereaccurately measured with EIT over a wide range of lung volume and minute ventilation. Wehave then described and validated a new model to obtain lung aerated volume and ventilationwith PET, without the requirement of gas sampling in the respiratory circuit. Finally, weconducted a controlled study with PET to evaluate the effects of positive end-expiratorypressure and body position on regional lung inflammation, ventilation and perfusion.Inflammation was significantly higher in injured groups than in control. However, there wasno significant change in inflammation across ALI groups despite significant differencebetween ventilation and perfusion repartition.We have developed in this work a stable experimental model of acute lung injury andvalidated noninvasive imaging tools allowing studying of important physiologic parametersthat could help setting up mechanical ventilation.

Nonobstant d’immenses progrès accomplis depuis des décennies dans la prise en charge des patients soumis à la ventilation mécanique, les pneumonies acquises sous ventilation mécanique continuent de compliquer le séjour en réanimation de près de 28% des patients recevant une assistance respiratoire invasive prolongée. Parmi les malades des unités de soins intensifs, le risque de développer une pneumonie est de 3 à 10 fois supérieur chez les intubés sous ventilation. Elle reste cependant bien souvent le seul moyen de venir en aide aux patients souffrant de graves détresses respiratoires. Il a maintenant été clairement démontré que la ventilation mécanique, en particulier lorsqu’elle est mise en place selon des stratégies dites agressives, active les cellules pulmonaires conduisant alors à une réponse pro-inflammatoire même en l’absence de pathogène. Ce phénomène est connu sous le terme de biotrauma, et serait responsable en partie des lésions induites sur le poumon par la ventilation mécanique. En quelques sortes, la ventilation mécanique prépare les cellules épithéliales pulmonaires à répondre massivement à une seconde agression pro-inflammatoire par la libération de grandes quantités de cytokines (comme l’IL-8 notamment), accentuant alors les lésions du tissu pulmonaire essentiellement par le recrutement de polynucléaires neutrophiles attirés par la sécrétion massive d’IL-8. L’immunité innée joue donc un rôle très important dans le développement du VILI. L’implication des Toll Like Récepteurs a été suggérée par plusieurs études expérimentales. Par ailleurs, la ventilation en décubitus ventral a été décrite pour avoir des effets bénéfiques sur les patients ventilés souffrant de graves lésions pulmonaires particulièrement chez ceux souffrant du syndrome de détresse respiratoire aiguë. Notre équipe s’est particulièrement intéressée au TLR2, qui reconnait les bactéries à Gram-positif, car elle a montré dans des études précédentes in vitro que l’étirement cyclique de cellules pulmonaires humaines augmentait principalement l’expression de TLR2 ainsi que la réactivité de cellules pulmonaires à des composants de la paroi de bactéries à Gram positif. Ces données ont par la suite été confirmées dans un modèle in vivo de lapins ventilés dont la réponse immune innée était stimulée par du Pam3CSK4.Dans un premier projet, nous avons évalué l’impact d’une ventilation mécanique en décubitus ventral chez des lapins avec pneumonie unilatérale à Enterobacter aerogenes soumis à la ventilation mécanique. Nos résultats montrent que le décubitus ventral peut être protecteur si l’hôte est soumis à la ventilation mécanique dans le contexte d’une pneumonie bactérienne unilatérale.Pour vérifier la pertinence de nos hypothèses sur le TLR2 dans notre modèle animal de pneumonie acquise sous ventilation mécanique, nous avons mené des expériences avec des bactéries vivantes reconnues par le TLR2 (une souche de Staphylococcus aureus résistante à la methicilline SARM). Notre étude met en évidence qu’une ventilation mécanique modérément agressive impacte sur la clairance bactérienne pulmonaire en la diminuant, aggrave les lésions sur le tissu pulmonaire et favorise une réponse inflammatoire systémique. La surexpression du TLR2 tant au niveau pulmonaire que systémique pourrait expliquer ces résultats.Le troisième projet s’est attaché à évaluer l’impact d’une thérapie aux statines dans le contexte d’une pneumonie acquise sous ventilation mécanique à SARM, conjointement traitée par le linezolide, dans notre modèle animal de lapins ventilés. Nos résultats suggèrent qu’une pré-­‐exposition aux statines pourrait avoir un effet anti-inflammatoire au niveau pulmonaire et systémique dans ce modèle, qui pourrait passer par une régulation négative de l’expression de TLR2, contre-balançant les effets de l’étirement cyclique. / Despite major advances since decades in the management of ventilated patients, ventilator-associated pneumonia (VAP) continues to complicate the course of approximately 28% of the patients receiving mechanical ventilation (MV). Among patients hospitalized in intensive care units, the risk of pneumonia is 3- to 10- fold increased in MV patients. However, MV is often the only way to care for critically ill patients with respiratory failure. It has now been clearly demonstrated that MV, in particular adverse ventilatory strategies could activate lung cells, thus leading to a proinflammatory response, even in the absence of pathogen. This is the biotrauma paradigm, which accounts, at least in part, for the ventilator induced lung injury (VILI). In one way, MV primes airway cells to respond massively to a second proinflammatory insult, through the subsequent release of large amounts of cytokines (as interleukin (IL)‐ 8), thus leading to additional lung injury, particularly through the recruitment of neutrophils attracted by the massive release of IL-8. Accordingly, innate immunity plays an important role in the developement of VILI. The involvement of Toll-like receptors has been suggested by several experimental studies. Ventilation in the prone position (PP) has been described to have beneficial effects on patients under MV, especially in those with lobar involvement. Our team focused particularly on the TLR2, which interacts with Gram-positive bacteria, and we have previously demonstrated in vitro that cyclic stretch of human pulmonary cells resulted in TLR2 overexpression and enhanced TLR2 reactivity to Gram-positive cell wall components. We confirmed these datas in an in vivo model of ventilated rabbits which immune response had been stimulated with Pam3CSK4. In a first project, we assessed the impact of the PP on unilateral pneumonia to Enterobacter aerogenes in rabbits subjected to MV. Our results shows that the prone position could be protective if the host is subjected to MV and unilateral bacterial pneumonia. To ensure the relevance of our hypothesis on TLR2 in our animal model of VAP, we conducted experiments using live bacteria specifically recognized by TLR2 (Methicilin resist. aureus). We demonstrate that mild-­‐stretch MV impaired lung bacterial clearance, hastened tissue injury and promoted a systemic inflammatory response. Both pulmonary and peripheral blood TLR2 overexpression could account for such an impact. The third project assessed the impact of a statins therapy in the context of MRSA VAP, treated with linezolid, in our model of ventilated rabbits. Our results suggest that statin exposure prior to pneumonia provides an anti-­‐inflammatory effect within the lung and the systemic compartment of rabbits with MRSA VAP. Although LNZ enhances pulmonary bacterial clearance, dampening the host systemic inflammatory response with statin could impede defense against MRSA in this compartment. It could be subsequent to enhanced antibacterial defences and improvements in lung mechanics, thereby blunting overwhelming inflammation. In the last project, in collaboration with the University of Geneva, we assessed whether mitochondrial alarmins are released during VILI and can generate lung inflammation. Our results confirmed the hypothesis made and showed indeed that alarmins are released during during cyclic stretch of human epithelial cells, as well as in BAL fluids from rabbits ventilated with an injurious ventilatory regimen. These alarmins stimulate lung cells to produce bioactive IL-­‐1, and are likely to represent the proximal endogenous mediators of VILI and ARDS, released by injured pulmonary cells.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-02-26T13:39:38Z No. of bitstreams: 1 aydramendesalmeidabianchi.pdf: 1447064 bytes, checksum: 5e432ac627c643fd1832440690fe8539 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-03-03T14:05:06Z (GMT) No. of bitstreams: 1 aydramendesalmeidabianchi.pdf: 1447064 bytes, checksum: 5e432ac627c643fd1832440690fe8539 (MD5) / Made available in DSpace on 2016-03-03T14:05:06Z (GMT). No. of bitstreams: 1 aydramendesalmeidabianchi.pdf: 1447064 bytes, checksum: 5e432ac627c643fd1832440690fe8539 (MD5) Previous issue date: 2015-03-09 / FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais / Introdução: A posição prona tem sido estudada como estratégia ventilatória em pacientes com síndrome do desconforto respiratório agudo. Seus benefícios, inclusive com redução da mortalidade, estão bem estabelecidos nas formas graves da síndrome, mas não em formas mais leves. Objetivo: Investigar o efeito da posição prona nas trocas gasosas, inflamação e histologia pulmonar, em modelo experimental de lesão pulmonar aguda leve em ratos. Métodos: A lesão pulmonar aguda foi induzida em ratos Wistar, machos, adultos, através da injeção de lipopolissacarídeo da Escherichia coli (5 mg/Kg). Após 24 h, os animais com PaO2/FIO2 entre 200 e 300 mmHg foram anestesiados e randomizados dentro de 2 grupos de acordo com a sua posição durante a ventilação (prona [n=6] e supina [n=6]). Ambos os grupos foram comparados com um grupo controle [n=5] que recebeu solução salina a 0,9% intraperitoneal e foi ventilado em posição supina. Todos os grupos foram ventilados por 1 h em modo ventilatório volumecontrolado, com volume corrente de 6 ml/Kg, frequência respiratória de 80 irpm, pressão positiva ao final da expiração de 5 cmH2O e uma fração inspirada de oxigênio de 1. Resultados: O escore de lesão pulmonar foi significativamente maior no grupo LPS-supino, em comparação com os grupos LPS-prono e controle (0,32 ± 0,03; 0,17 ± 0,03 e 0,13 ± 0,04, respectivamente) (p < 0,001), devido a uma maior infiltração de neutrófilos no espaço intersticial e maior presença de debris proteicos na luz alveolar. Esta maior lesão pulmonar no grupo LPS-supino foi observada tanto nas regiões pulmonares dependentes da gravidade (dorsal no grupo supino e ventral no grupo prono – 0,34 ± 0,05 e 0,22 ± 0,04, respectivamente) (p < 0,05), quanto nas não dependentes (ventral no grupo supino e dorsal no grupo prono – 0,29 ± 0,04 e 0,13 ± 0,04, respectivamente) (p < 0,05). O contagem de neutrófilos no LBA foi maior no grupo LPS-supino, comparado com os grupos LPS prono e controle. Não houve diferenças significativas na relação peso úmido/peso seco e nas trocas gasosas entre os três grupos. Conclusões: Neste modelo experimental de lesão pulmonar aguda leve extrapulmonar, a ventilação em posição prona por 1 hora, quando comparada com a ventilação em posição supino, associou-se a menor lesão e inflamação pulmonar, mas sem impacto na oxigenação arterial e no edema pulmonar. / Introduction: Prone position has been studied as a ventilator strategy among patients with acute respiratory distress syndrome. The benefits of prone position ventilation, including reduction in the mortality, are well demonstrated in the severe but not in milder forms of this syndrome. We therefore investigated the effects of the prone position on arterial blood gases, lung inflammation and histology in an experimental model of mild acute lung injury in rats. Methods: Acute lung injury was induced in adult male Wistar rats by intraperitoneal Escherichia coli lipopolysaccharide injection (5 mg/kg). After 24h, the animals with PaO2/FIO2 between 200 and 300 mmHg were anesthetized and randomized into 2 groups according to their position during ventilation (prone [n=6] and supine [n=6]). Both groups were compared to a control group (n=5) that received intraperitoneal saline and was ventilated in the supine position. All of the groups were ventilated for 1h with volume-controlled ventilation mode, with tidal volume of 6 ml/kg, respiratory rate of 80 breaths/min, positive end-expiratory pressure of 5 cmH2O, and an inspired oxygen fraction of 1. Results: Significantly higher lung injury scores were observed in the LPS-supine group compared to LPS-prone and control groups (0.32 ± 0.03; 0.17 ± 0.03 and 0.13 ± 0.04, respectively) (p<0.001), mainly due to a higher neutrophil infiltration level in the interstitial space and more proteinaceous debris in the airspaces. Similar differences were observed when the gravitational dependent lung regions (dorsal in the supine group and ventral in the prone group – 0.34 ± 0.05 and 0.22 ± 0.04, respectively) (p < 0.05) and non-dependent lung regions (ventral in the supine group and dorsal in the prone group – 0.29 ± 0.04 and 0.13 ± 0.04, respectively) (p < 0.05) were analyzed separately. The BAL neutrophil content was also higher in the LPS-supine group compared to the LPSprone and control groups. There were no significant differences in the wet/dry ratio and gas exchange levels among the three groups. CONCLUSIONS: In this experimental extrapulmonary mild acute lung injury model, prone position ventilation for 1 hour, when compared with supine position ventilation, was associated with lower lung inflammation and injury, but without any impact on arterial oxygenation and lung edema.

Introduction: La pneumonie associée à la ventilation mécanique (VM) est fréquente chez les patients ventilés. L’étirement cyclique (EC) induit par la VM pourrait amorcer le poumon vers une réponse inflammatoire en cas d'exposition à des bactéries. Les Toll-like Receptors (TLR) reconnaissent les bactéries et déclenchent l'immunité. La VM pourrait moduler l'expression des TLR et leur réactivité aux agonistes. Le décubitus ventral (DV) réduit l’étirement du poumon. Méthodes: Les niveaux de TLR2 et la réponse à ses agonistes ont été mesures dans des cellules pulmonaires soumises à un EC, et dans un modèle de lapin ventilé. Une stimulation ex vivo du sang total prélevé sur lapins ventilés a été réalisée. Une pneumonie a été induite chez des lapins soumis à VM et maintenus en décubitus dorsal ou tournés en DV. Résultats: L’EC des cellules ainsi que des poumons de lapins augmente les niveaux de TLR2 et la réponse inflammatoire à ses agonistes. La VM et l’exposition du poumon à des agonistes TLR2 induisent synergiquement des lésions. Chez des lapins avec pneumonie sous VM la clairance bactérienne pulmonaire est réduite, la probabilité de bactériémie et le taux des cytokines circulantes augmentés. Le sang total provenant d'animaux sous VM libère de grandes quantités de cytokines après stimulation. Le DV est associe à des niveaux plus faibles de concentrations bactériennes et d'inflammation. Conclusions: La VM sensibilise le poumon aux ligands bactériens de TLR2, modifie la clairance bactérienne pulmonaire, favorise les lésions pulmonaires et de l'inflammation. La surexpression de TLR2 induite par l’EC pourrait expliquer ces différences. Le DV pourrait avoir un effet protecteur. / Introduction: Ventilator-associated pneumonia is common in patients subjected to mechanical ventilation (MV). Cyclic stretch subsequent to MV could prime the lung toward an inflammatory response if exposed to bacteria. Toll-like receptors (TLRs) recognize pathogens thus triggering immunity. MV could modulate TLRs expression and responsiveness to agonists. The prone position (PP) reduces lung stretch.Methods:TLR2 levels and response to the TLR2 ligands were measured in human pulmonary cells submitted to cyclic stretch, and either spontaneously breathing (SB) or MV rabbits. Ex vivo stimulation of whole blood taken from SB or MV rabbits was performed.Enterobacter aerogenes pneumonia was induced in rabbits subjected to MV and kept supine or turned to the PP. Results: Cyclic stretch of human cells as well as rabbitsÕ lung increased both TLR2 levels and inflammatory response to its agonist. MV and airways exposure to TLR2 ligands acted synergistically in causing lung injury.A decrease of lung bacterial clearance and a greater likelihood of bacteremia were observed in MV rabbits with S. aureus pneumonia. Circulating cytokines rose significantly only in these animals. MV induced TLR2 spleen overexpression. Whole blood obtained from MV animals released larger amounts of cytokines after stimulation. PP was associated with lower levels of bacterial concentrations and inflammation. Conclusions: MV sensitizes the lung to bacterial TLR2 ligands, alters lung bacterial clearance, promotes lung injury and inflammation. Both pulmonary and peripheral blood stretch-induced TLR2 overexpression could account at least in part for such differences. The PP could be protective.