Injury from blast is significant in both military and civilian environments. Although injuries from blast are well-documented, the mechanisms of injury are not well understood. Developing better protection requires knowledge of injury mechanisms and material response to blast loading. The importance of understanding how soft materials such as foams and fabrics behave under blast loading is further apparent when one realizes the capacity for some of these materials, frequently used in protective ensembles, to increase the potential for injury under some conditions. The ability for material configurations to amplify blast pressure and injury has been shown experimentally by other researches, and numerically in this study. Initially, 1-D finite element and mathematical models were developed to investigate a variety of soft materials commonly utilized in ballistic and blast protection. Foams, which have excellent characteristics in terms of energy absorption and density, can be used in conjunction with other materials to drastically reduce the amplitude of the transmitted pressure wave and corresponding injury. Additionally, a more fundamental examination of single layers of fabric was undertaken to investigate to the effects of parameters such as fabric porosity and density. Shock tube models were developed and validated against experimental results from the literature. After the models were validated, individual fabric properties were varied independently to isolate the influence of parameters in ways not possible experimentally. Fabric permeability was found to have the greatest influence on pressure amplification. Kevlar, a ballistic fabric, was modelled due to its frequent use for fragmentation protection (either stand-alone or in conjunction with a hard ballistic plate). The developed fabric and foam material models were then utilized in conjunction with a detailed torso model for the estimation of lung injury resulting from air blast. It was found that the torso model predicted both amplification and attenuation of injury, and all materials investigated as a part of the study had the capacity for both blast amplification and attenuation. The benefit of the models developed is that they allow for the evaluation of specific protection concepts.

Injury from blast is significant in both military and civilian environments. Although injuries from blast are well-documented, the mechanisms of injury are not well understood. Developing better protection requires knowledge of injury mechanisms and material response to blast loading. The importance of understanding how soft materials such as foams and fabrics behave under blast loading is further apparent when one realizes the capacity for some of these materials, frequently used in protective ensembles, to increase the potential for injury under some conditions. The ability for material configurations to amplify blast pressure and injury has been shown experimentally by other researches, and numerically in this study. Initially, 1-D finite element and mathematical models were developed to investigate a variety of soft materials commonly utilized in ballistic and blast protection. Foams, which have excellent characteristics in terms of energy absorption and density, can be used in conjunction with other materials to drastically reduce the amplitude of the transmitted pressure wave and corresponding injury. Additionally, a more fundamental examination of single layers of fabric was undertaken to investigate to the effects of parameters such as fabric porosity and density. Shock tube models were developed and validated against experimental results from the literature. After the models were validated, individual fabric properties were varied independently to isolate the influence of parameters in ways not possible experimentally. Fabric permeability was found to have the greatest influence on pressure amplification. Kevlar, a ballistic fabric, was modelled due to its frequent use for fragmentation protection (either stand-alone or in conjunction with a hard ballistic plate). The developed fabric and foam material models were then utilized in conjunction with a detailed torso model for the estimation of lung injury resulting from air blast. It was found that the torso model predicted both amplification and attenuation of injury, and all materials investigated as a part of the study had the capacity for both blast amplification and attenuation. The benefit of the models developed is that they allow for the evaluation of specific protection concepts.

Bei IL-10 handelt es sich um ein antiinflammatorisches Zytokin, dessen immunmodulatorische Effekte bereits in zahlreichen Studien aufgezeigt werden konnten. Ziel dieser Studie war, die Unterschiede in der systemischen Inflammation und Organdysfunktion an Mäusen zu untersuchen, die nach Induktion eines hämorrhagischen Schocks, entweder inhalativ oder systemisch, mit IL-10 behandelt wurden. Männliche C57/BL6 Mäuse (6 Tiere pro Gruppe) wurden für 1.5 Stunden blutdruckkontrolliert in einen hämorrhagischen Schock versetzt. Nach anschließender Volumensubstitution wurde ihnen inhalativ oder intraarteriell rekombiniertes Maus - IL-10 verabreicht. Nach einer Gesamtversuchsdauer von 6 - bzw. 24 Stunden erfolgte die Tötung der Tiere. Die Ergebnisse der Studie zeigen, dass die lokale und systemische Verabreichung von IL-10 das Zytokinprofil der systemischen Inflammationsantwort unterschiedlich beeinflusst. Die Lunge kann durch inhalative Gabe von IL-10 geschützt werden, ohne die systemische Inflammationsantwort zu beeinflussen.

Bei Patienten mit einem akuten Lungenversagen (ALI oder ARDS) ist der Sauerstoffverbrauch der Lunge (VO2pulm) durch pathophysiologische Prozesse insbesondere die Ausbildung von Atelektasen stark beeinträchtigt. Aufgrund der Annahme, dass eine Steigerung der Anzahl ventilierter Lungenareale zu einer Erhöhung des pulmonalen Sauerstoffverbrauchs führt, haben wir den Einfluss eines definierten Rekrutierungsmanövers (PEEP/PEAK + 10 cmH2O) auf den pulmonalen Sauerstoffverbrauch (VO2pulm), pulmonalen kapillären Blutfluss (PCBF), der den nicht geshunteten Anteil am HZV darstellt, und den transpulmonalen Shunt (Qs/Qt) untersucht. In der vorliegenden Studie wurde der VO2pulm als Differenz zwischen dem Sauerstoffverbrauch des gesamten Körpers, gemessen über die indirekte Kalorimetrie (VO2cal), und dem über das inverse Fick`sche Prinzip errechneten Sauerstoffverbrauch (VO2Fick) bestimmt. Im Rahmen einer klinisch-prospektiven Studie konnten nach Annahme des Studienprotokolls durch die zuständige Ethikkommission 13 beatmete Patienten, welche die Consensus-Kriterien eines ALI oder ARDS erfüllten, eingeschlossen werden. Nach Sicherstellung einer adäquaten Volumensituation und Messung der Ausgangsparameter wurde der PEEP um 10 cmH2O erhöht. Um ein stabiles Atemzugvolumen (VT 6-8 ml/kgKG) und damit gleichbleibende Bedingungen für die alveoläre Ventilation bis auf das von uns durchgeführte Rekrutierungsmanöver zu gewährleisten, wurde zeitgleich der Spitzendruck ebenfalls um 10 cmH2O erhöht. Nach 15 und 60 min wurden die Zieldeterminanten pulmonaler Sauerstoffverbrauch (VO2pulm), PCBF und transpulmonaler Shunt erneut bestimmt. Die Messung der indirekten Kalorimetrie (VO2cal) wurde mit dem Deltatrac TM, MBM 200® durchgeführt, VO2Fick über die Thermodilutionsmethode ermittelt, die partielle CO2-Rückatmungsmethode (David®) zur Bestimmung des PCBF genutzt und der transpulmonale Shunt (Qs/Qt) mittels der Formel nach BERGGREN berechnet. Die statistische Auswertung der Daten erfolgte mittels T-Tests für gepaarte Stichproben. Nach dem Manöver konnte eine signifikante Steigerung des PCBF von 4,44 ± 1,15 l/min auf 5,4 ± 1,68 l/min nach 15 min, respektive 5,12 ± 1,67 l/min nach 60 min nachgewiesen werden (p<0,025). Dieser Anstieg wurde von einer signifikanten Reduktion des transpulmonalen Shunts (Qs/Qt) von 0,24 ± 0,08 auf 0,16 ± 0,07 nach 15 min und 0,16 ± 0,07 nach 60 min begleitet (p<0,005). Diese Veränderungen der pulmonalen Hämodynamik gehen mit statistisch relevanten Verbesserungen der Oxygenierung sowie der Atemmechanik einher. Eine signifikante Steigerung des pulmonalen Sauerstoffverbrauchs konnte für die gesamte Studienpopulation nicht festgestellt werden. In dieser Untersuchung steigt der Sauerstoffverbrauch der Lunge deskriptiv von baseline 10,1 +/- 30,59 ml/min über 11,42 +/- 27,42 ml/min nach 15 min, respektive auf 28,69 +/- 56,75 ml/min nach 60 min an. Die signifikante Steigerung des pulmonal-kapillären Blutflusses und die konsekutive Reduktion des transpulmonalen Shunts schon 15 min nach dem Manöver impliziert einen Anstieg der an der alveolären Ventilation teilnehmenden alveolokapillären Einheiten, was einer Rekrutierung von vorher atelektatischen Lungenabschnitten entspricht. Insbesondere bei ARDS-Patienten und Respondern konnten Rekrutierungs-induzierte Veränderungen detektiert werden, wohingegen die Patienten mit ALI oder Nonresponder keinerlei statistische Unterschiede während der Intervention zeigten. Trotz stattgefundener Wiederbelüftung von Atelektasen konnte ein statistisch relevanter Unterschied bezüglich des pulmonalen Sauerstoffverbrauchs durch das Rekrutierungsmanöver für die gesamte Studienpopulation nicht festgestellt werden.

The acute respiratory distress syndrome (ARDS) and its less severe form, acute lung injury (ALI), are among the leading causes of morbidity and mortality in critically ill patients. Commonly induced by conditions associated with severe pulmonary inflammation, ALI results in disruption of the lung alveolar-capillary membrane barrier and resultant pulmonary edema associated with a proteinaceous alveolar exudate. Sepsis is another frequent and often fatal clinical condition for patients in the intensive care unit. It is characterized by a combination of infection and systemic inflammatory response syndrome (SIRS). Current effective treatment strategies for both ALI/ARDS and sepsis are lacking. We first examined the potential therapeutic role of mesenchymal stromal cells (MSCs) alone or together with the vasculoprotective factor, angiopoietin-1 (ANGPT1), for treatment of experimental ALI in mice. MSCs significantly reduced LPS (lipopolysaccharide)-induced pulmonary inflammation, as reflected by cell counts in bronchoalveolar lavage (BAL) fluid and pro-inflammatory cytokine levels in both BAL fluid and lung parenchymal homogenates. More importantly, administration of MSCs transfected with human ANGPT1 plasmid (MSCs-pANGPT1) completely reversed LPS-induced permeability in the lung (i.e., ALI). A follow-up study showed that MSCs remained effective in rescuing mice with LPS-induced ALI; however, the additional benefit from ANGPT1 was no longer observed. To further evaluate MSC-based therapy in a more clinically relevant model of acute injury, the cecal-ligation-and-puncture (CLP) model for sepsis was employed. Our results demonstrated that MSCs can reduce both systemic and pulmonary inflammation, as well as renal and liver dysfunction/injury, as reflected by plasma urea and bilirubin levels, in septic mice. Most notably, MSCs reduced sepsis-associated mortality from 45% to 24%. Our data demonstrate the feasibility and effectiveness of MSC- and MSC-based gene therapy for experimental ALI and sepsis, and provide the basis for the development of an innovative approach for the prevention and treatment of clinical ALI/ARDS and sepsis.

The acute respiratory distress syndrome (ARDS) and its less severe form, acute lung injury (ALI), are among the leading causes of morbidity and mortality in critically ill patients. Commonly induced by conditions associated with severe pulmonary inflammation, ALI results in disruption of the lung alveolar-capillary membrane barrier and resultant pulmonary edema associated with a proteinaceous alveolar exudate. Sepsis is another frequent and often fatal clinical condition for patients in the intensive care unit. It is characterized by a combination of infection and systemic inflammatory response syndrome (SIRS). Current effective treatment strategies for both ALI/ARDS and sepsis are lacking. We first examined the potential therapeutic role of mesenchymal stromal cells (MSCs) alone or together with the vasculoprotective factor, angiopoietin-1 (ANGPT1), for treatment of experimental ALI in mice. MSCs significantly reduced LPS (lipopolysaccharide)-induced pulmonary inflammation, as reflected by cell counts in bronchoalveolar lavage (BAL) fluid and pro-inflammatory cytokine levels in both BAL fluid and lung parenchymal homogenates. More importantly, administration of MSCs transfected with human ANGPT1 plasmid (MSCs-pANGPT1) completely reversed LPS-induced permeability in the lung (i.e., ALI). A follow-up study showed that MSCs remained effective in rescuing mice with LPS-induced ALI; however, the additional benefit from ANGPT1 was no longer observed. To further evaluate MSC-based therapy in a more clinically relevant model of acute injury, the cecal-ligation-and-puncture (CLP) model for sepsis was employed. Our results demonstrated that MSCs can reduce both systemic and pulmonary inflammation, as well as renal and liver dysfunction/injury, as reflected by plasma urea and bilirubin levels, in septic mice. Most notably, MSCs reduced sepsis-associated mortality from 45% to 24%. Our data demonstrate the feasibility and effectiveness of MSC- and MSC-based gene therapy for experimental ALI and sepsis, and provide the basis for the development of an innovative approach for the prevention and treatment of clinical ALI/ARDS and sepsis.

Nitric oxide (NO) is an important regulator of pulmonary blood flow and attenuates hypoxic pulmonary vasoconstriction (HPV). Nitric oxide is synthesized enzymatically in a number of tissues, including the lungs, and can also be generated from reduction of nitrite during hypoxia and acidosis. Inhaled nitric oxide (INO) is a selective pulmonary vasodilator, with no effects on systemic arterial blood pressure due to inactivation by hemoglobin in the blood. INO has distant effects both within the lungs and in other organs, since NO can be transported to remote tissues bound to proteins, or as more stable molecules of nitrite and nitrate. In healthy pigs, INO causes vasoconstriction and down regulation of endogenous NO production in lung regions not reached by INO, and predominantly so in hypoxic lung regions, i.e. augmentation of HPV. In this thesis, distant effects of INO in pigs with endotoxemic- and lavage-induced lung injuries were studied. INO increased the NO production in lung regions not reached by INO in endotoxemic pigs, whereas endogenous NO production was unaffected in pigs with lavage-induced injury. Metabolic and/or hypercapnic acidosis frequently occurs in critically ill patients, but whether acidosis affects the endogenous pulmonary NO production is unclear. The regional NO production and blood flow in hyperoxic and hypoxic lung regions, were studied during metabolic and hypercapnic acidosis. Neither metabolic, nor hypercapnic acidosis changed the endogenous NO production in hyperoxic or hypoxic lung regions. Metabolic acidosis potentiated HPV, whereas hypercapnic acidosis transiently attenuated HPV. In conclusion, the present thesis has demonstrated that INO in experimental sepsis increases the endogenous NO production in lung regions not reached by INO, which may cause increased shunt and poor response to INO. This distant effect is not seen in lavage injuried lungs, an experimental model with less inflammation. Acidosis does not affect the endogenous pulmonary NO production in hyperoxic or hypoxic lung regions. Whereas metabolic acidosis potentiates HPV, hypercapnic acidosis transiently attenuates HPV, due to a combination of hypercapnia-induced increase in cardiac output and a probable vasodilating effect of the CO2-molecule.

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 Maike Costa (maiksebas@gmail.com) on 2017-07-07T15:09:57Z No. of bitstreams: 1 arquivototal.pdf: 1854233 bytes, checksum: 535d273c615cebce265419e27f74439a (MD5) / Made available in DSpace on 2017-07-07T15:09:57Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 1854233 bytes, checksum: 535d273c615cebce265419e27f74439a (MD5) Previous issue date: 2016-10-17 / Ouabain is a cardiotonic steroid initially described as a substance of plant origin. In 1991, the endogenous production of higher mammals was identified and since then their physiological actions have been studied. Work of our group have demonstrated that ouabain modulates the acute inflammatory response induced by different phlogistic agents, also being able to interfere negatively in inflammatory profile triggered by Leishmania (L.) amazonensis. Acute lung injury (ALI) is a serious inflammatory disease characterized by acute inflammation, extensive accumulation of polymorphonuclear leukocytes and accumulation of proinflammatory mediators, which culminates with diffuse alveolar damage and which may cause the patient died due to severe hypoxemia. There is no data in the literature on the effects of ouabain in ALI. Objectives: Evaluate the immunomodulatory effect of ouabain in a murine model of ALI induced by LPS. Methods: BALB / c mice were treated intraperitoneally with ouabain at a dose of 0.56 mg / kg for a period of three consecutive days, 1 hour after the last treatment the animals were challenged intranasally with 40μl of an LPS solution (2 5 mg / kg); 24 hours after challenge, the animals were euthanized, the collected biological sample and inflammatory parameters, including cell migration, protein exudates, cytokine production, TLR4 expression and histopathological changes were then evaluated. Data were analyzed by PRISMA software. Results: The treatment with ouabain decreased total leukocytes migration to the inflamed site (48,84%), this event associated with decreased neutrophil migration (70,71%) and independent of macrophage migration. The ouabain also decreased the exudate protein in the broncho-alveolar region (26,32%) and production of the cytokines TNF-α (14,80%), IL-6 (47,07%) and IL1-β (33,59%), however this reduction in the production of these mediators was not related to the expression of TLR4. Additionally, the ALI histopathology changes were also reduced by treatment with ouabain. Conclusions: The results show that ouabain has anti-inflammatory action in ALI induced by LPS. / A Ouabaína é um esteroide cardiotônico inicialmente descrito como uma substância de origem vegetal. Em 1991, a sua produção endógena por mamíferos superiores foi identificada e desde então suas ações fisiológicas vêm sendo estudadas. Trabalhos do nosso grupo demonstraram que a ouabaína modula a resposta inflamatória aguda induzida por diferentes agentes flogísticos, sendo também capaz de interferir negativamente no perfil inflamatório desencadeado pela Leishmania (L.) amazonensis. A lesão pulmonar aguda (LPA) é uma doença inflamatória caracterizada por inflamação aguda e extenso acúmulo de polimorfonucleares e de mediadores pró-inflamatórios, que culmina com dano alveolar difuso podendo levar o paciente a óbito por hipoxemia severa. Não há dados na literatura sobre os efeitos da ouabaína na LPA. Objetivos: Avaliar o efeito imunomodulador de ouabaína em modelo murino de LPA induzida por LPS. Métodos: Camundongos BALB/c machos foram tratados via intraperitoneal com ouabaína na dose de 0,56 mg/Kg por um período de três dias consecutivos, 1h após o último tratamento os animais foram desafiados via intranasal com LPS (2,5 mg/Kg); 24h após o desafio, os animais foram eutanásiados, as amostras biológicas coletadas e os parâmetros inflamatórios, incluindo migração celular, exsudato proteico, produção de citocinas, expressão de TLR4 e alterações histopatológicas foram então avaliados. Os dados foram analisados pelo software PRISMA. Resultados: O tratamento com a ouabaína diminuiu a migração de leucócitos totais para o sítio inflamado (48,84%), evento este, associado a diminuição da migração de neutrófilos (70,7%) e independente da migração de macrófagos. Ouabaína também diminuiu o exsudato proteico na região bronco-alveolar (26,32%) e a produção das citocinas TNF-α (14,80%), IL-6 (47,07%) e IL1-β (33,59%), entretanto essa redução na produção desses mediadores não mostrou relação com a expressão do TLR4. Adicionalmente, as alterações histopatológicas características da LPA também foram reduzidas pelo tratamento com ouabaína. Conclusões: Os resultados obtidos demonstram que ouabaína possui ação anti-inflamatória na LPA induzida por LPS.

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