INTRODUÇÃO. O termo Lesão Pulmonar Aguda (LPA) é usado para descrever a resposta pulmonar à lesão que ocorre diretamente ou indiretamente nos pulmões. A quebra da barreira alvéolo-capilar determina o influxo de líquido rico em proteínas para dentro dos espaços alveolares, sendo necessária a reabsorção desse líquido no processo de resolução da LPA. A infusão intravenosa de Ácido Oleico (AO) em ratos provoca agudamente edema alveolar difuso e focos hemorrágicos intra-alveolares, sendo um bom modelo de indução. Estudos relatam que o Azul de Metileno (AM) atenua tais lesões, com efeito protetor, no tecido pulmonar, e reduz o edema presente na LPA em animais com sepse através da inibição da guanilato ciclase solúvel (GCs), uma enzima ativadora da via NO-GMPc. OBJETIVO. Estudar a repercussão da inibição da GCs pelo AM na permeabilidade capilar pulmonar ministrando-o antes e após a indução da lesão pulmonar por AO. MÉTODO. Ratos Wistar foram divididos em 5 grupos: Sham com infusão de salina em bolus; AM com infusão de AM por 2h; AO com infusão de AO em bolus, AM/AO com infusão de AM por 2h, sendo que, após 5 min do início, recebeu AO simultaneamente em bolus e AO/AM com infusão de AO em bolus e, após 2h, infusão de AM por mais 2h. Após 4h foi realizada a coleta de materiais (sangue, lavado bronco-alveolar e tecido pulmonar) para análise do NO plasmático e tecidual, gasometria arterial, cálculo do peso úmido/peso seco (PU/PS) e histologia do tecido pulmonar de todos os grupos. A estatística utilizada foi a análise de variância (one-way ANOVA) com p<0.05. RESULTADO. Não foi encontrado hipoxemia grave após 4h de lesão. O grupo AO apresenta um aumento no número de proteínas no lavado bronco-alveolar e na relação PU/PS comparado aos grupos controle: Sham e AM, confirmando a presença de lesão e alteração de permeabilidade pulmonar. Os grupos tratados com AM apresentaram melhora na permeabilidade pulmonar, porém, apenas o grupo pré-tratamento (AM/AO) apresentou diferença estatística na redução do extravasamento de proteínas no lavado. Não foram encontradas diferenças significativas no NO plasmático e tecidual. Na microscopia, a congestão capilar foi intensa, acompanhada de múltiplos focos de edema alveolar, exsudato intra-alveolar proteico, áreas de hemorragia e infiltrado inflamatório neutrofílico, tanto no interstício quanto nos septos alveolares.Os grupos tratados com AM apresentaram diminuição das áreas de edema, exsudação e hemorragia, porém, com maior evidência no grupo AM/AO. CONCLUSÃO. O AM diminui a permeabilidade pulmonar quando administrado de maneira precoce amenizando os danos causados pela LPA induzida por AO. / BACKGROUND. The term Acute Lung Injury (ALI) is used to describe the response to lung injury that occurs directly or indirectly in the lungs. The rupture of the alveolar - capillary barrier determines the influx of protein-rich fluid into the alveolar spaces, the reabsorption of this fluid in the process of resolving the ALI is required. Intravenous infusion of oleic acid (OA) in rats acutely causes diffuse alveolar edema and intra-alveolar hemorrhagic foci, being a good role model induction. Studies have reported that Methylene Blue (MB) attenuates such injuries, with a protective effect in lung tissue and reduce edema present in the ALI present in with sepsis by inhibition of soluble guanylate cyclase (sGC), an activator of the enzyme NO- cGMP pathway. OBJECTIVE. To study the effect of inhibition of sGC by MB in pulmonary capillary permeability ministering to the before and after induction of lung injury by OA. METHOD. Wistar rats were divided into 5 groups: Sham infused with saline bolus, MB infused with MB for 2hrs, OA infused with OA bolus, MB/OA infused with MB for 2hrs, and after 5 min from the beginning, simultaneously received OA bolus and OA/MB infused with OA bolus and after 2hrs, MB infusion for 2hrs. After 4hrs the collection of materials was performed (blood, bronchoalveolar lavage and lung tissue) for analysis of plasma and tissue NO, arterial blood gases, calculation of the wet weight/dry weight (WW/DW) and histology of lung tissue from all groups. The statistic used was analysis of variance (one-way ANOVA) with p<0.05. RESULTS. Not found severe hypoxemia after 4hrs of injury. The OA group shows an increase in the number of proteins in bronchoalveolar lavage and in WW/DW ratio compared to the control groups: Sham and MB, confirming the presence of injury and alterations of lung permeability. The groups treated with MB showed improvement in lung permeability, however, only the pretreatment group (MB/OA) showed statistical significance in reducing the leakage of protein in the lavage. No significant differences were found in plasma and tissue NO. In microscopy, capillary congestion was intense, accompanied by multiple foci of alveolar edema, intra-alveolar proteinaceous exudates, areas of hemorrhage and neutrophilic inflammatory infiltrate in both the interstitium and in the alveolar septa. The groups treated with MB showed reduction in areas of edema, exudation and hemorrhage, however, most obviously in MB/OA group. CONCLUSION. The MB decreases lung permeability when administered as early as possible, mitigating the damage caused by OA-induced ALI.

Introdução: A ventilação manual é um aspecto chave que determina a eficiência da ressuscitação neonatal e pode ser realizada por várias categorias de profissionais utilizando diferentes equipamentos. Objetivos: Comparar os efeitos da ventilação manual realizada por diferentes profissionais envolvidos na assistência neonatal, médicos, enfermeiros e fisioterapeutas, utilizando dois equipamentos: Peça T e balão autoinflável. Métodos: Coelhos adultos foram submetidos à ventilação manual utilizando Peça T ou balão autoinflável, 10 minutos com cada dispositivo, operado por médicos, fisioterapeutas e enfermeiros, num total de 21 indivíduos. A escolha do primeiro dispositivo utilizado por cada voluntário foi realizada por randomização. Os dados de mecânica respiratória (volume corrente, volume minuto, frequência respiratória, tempos inspiratório e expiratório, pressão inspiratória e pressão expiratória final positiva) foram obtidos de maneira contínua através de um sistema informatizado de aquisição de dados, cega para os operadores. Amostras de sangue arterial foram obtidas por cateterização da carótida antes e depois de cada ventilação manual para determinação da PaCO2 e do pH. Foram comparados os dispositivos entre si, assim como o desempenho dos grupos de profissionais com cada dispositivo. Resultados: Quando analisados todos os profissionais em conjunto (n = 21) os animais ventilados com o balão autoinflável apresentaram maior volume minuto, menor frequência respiratória, menor tempo inspiratório e maiores valores de pH após o período de 10 minutos de ventilação. Quando analisados separadamente cada um dos três grupos de profissionais, os animais ventilados com o balão autoinflável no grupo Enfermeiras (n = 7) apresentaram maior volume minuto (390±108 vs 766±410 mL/min, p < 0,05) em relação ao grupo Fisioterapeutas (n = 7) (418±192 vs 886±787 mL/min) e grupo Médicos (n = 7) (438±206 vs 705±434 mL/min). Resultados similares foram encontrados em relação ao pH após 10 minutos de ventilação manual, sendo observada no grupo Enfermeiras a ocorrência de alcalose respiratória (7,40±0,11 vs 7,61±0,02, p < 0,05, 7,37±0,10 vs 7,52±0,23, 7,36±0,07 vs 7,40±0,18 mL/min, respectivamente) e de hipocapnia (32,4±6,9 vs 23,4±7,5 mmHg, p < 0,05; 40,4±10,8 vs 28,0±15,2 mmHg, 38,0±13,8 vs 42,6±18,1 mmHg) respectivamente. Conclusão: O balão autoinflável resultou em hipocapnia e alcalose respiratória no grupo Enfermeiras, a ventilação manual utilizando a Peça T resultou em menor volume corrente e menor volume minuto / Introduction: Manual ventilation is a key aspect that determines the efficiency of neonatal resuscitation and can be performed by several categories of professionals using different equipment. Objectives: To compare the effects of manual ventilation performed by different professionals involved in neonatal care, physicians, nurses and physiotherapists, using two devices: T-piece and self-inflating bag. Methods: Adult rabbits were submitted to manual ventilation using T-piece or self-inflating bag, 10 minutes with each device, operated by physicians, physiotherapists and nurses, in a total of 21 individuals. The choice of the first device used by each volunteer was by randomization. Respiratory mechanics data (tidal volume, minute volume, respiratory rate, inspiratory and expiratory time, inspiratory pressure and positive end expiratory pressure) were obtained continuously through a computerized data acquisition system, blind to operators. Arterial blood gas samples were obtained through carotid catheterization before and after each manual ventilation for determination of PaCO2 and pH. The devices were compared to each other as well as the performance of groups of professionals with each device. Results: When all the professionals (n = 21) were analyzed together, the animals ventilated with the self-inflating bag presented higher minute volume, lower respiratory rate, shorter inspiratory time and higher pH values after 10 minutes of ventilation. When the three groups of professionals were analyzed separately, the animals ventilated with the self-inflating bag in the Nurse group (n = 7) had a higher minute volume (390±108 vs 766±410 mL/min, p < 0.05) compared to the Physiotherapists group (n = 7) (418±192 vs 886±787 mL/min) and the Physicians group (n = 7) (438±206 vs. 705±434 mL/min). Similar results were found in relation to pH after 10 minutes of manual ventilation, with the occurrence in the Nurses group of respiratory alkalosis (7.40±0.11 vs 7.61±0.02, p < 0.05, 7.37±0.10 vs 7.52±0.23, 7.36±0.07 vs 7.40±0.18 mL/min, respectively) and hypocapnia (32.4±6.9 vs 23.4±7.5 mmHg, p < 0.05; 40.4±10.8 vs 28.0 ± 15.2 mmHg, 38.0±13.8 vs. 42.6±18.1 mmHg) respectively. Conclusion: The self-inflating bag resulted in hypocapnia and respiratory alkalosis in the Nurses group, manual ventilation using T-piece resulted in lower tidal volume and minute volume

INTRODUÇÃO: A isquemia-reperfusão pulmonar e o uso do oxigenador de membranas são considerados fatores importantes na resposta inflamatória após a cirurgia cardíaca (CC) com utilização da circulação extracorpórea (CEC). Estudos anteriores que utilizaram os próprios pulmões dos pacientes como oxigenador em uma circulação extracorpórea biventricular (CECBV) em comparação à CEC convencional (CECC) mostraram efeitos benéficos na mecânica pulmonar e na reação inflamatória sistêmica. No entanto, a inflamação pulmonar ainda não foi totalmente esclarecida neste cenário. Os objetivos deste estudo foram observar o impacto da exclusão do oxigenador de membranas e da manutenção da ventilação e perfusão pulmonar na inflamação regional em porcos submetidos à CEC. MÉTODOS: Vinte e sete porcos ventilados mecanicamente foram submetidos à toracotomia e alocados randomicamente nos grupos: Controle (n=8), CECC (n=9) e CECBV (n=10). Os animais dos grupos CECC e CECBV foram submetidos respectivamente a uma CEC convencional ou a uma CEC biventricular com ventilação e perfusão pulmonar sem oxigenador de membranas por 90 minutos. As interleucinas (ILs) séricas foram avaliadas nos momentos: basal, após a CEC e 90 minutos após a CEC, e em momentos equivalentes no grupo Controle. As ILs do lavado broncoalveolar (LBA) foram medidas nos momentos basal e 90 minutos após a CEC. Amostras de tecido pulmonar foram coletadas da região ventral e dorsal do lobo pulmonar esquerdo para avaliação do número de polimorfonucleares (PMN) e quantificação do edema pela área de parênquima. Os dados foram avaliados através de ANOVA, considerando-se estatisticamente significante p<0,05. RESULTADOS: O grupo CECC apresentou uma maior inflamação, com um aumento no número de PMN, comparado ao grupo Controle (p < 0,001) nas regiões: ventral (2,8 x10-6± 0,7 x10-6 vs. 1,6 x10-6 ± 0,5 x10-6 , respectivamente) e dorsal (3,3 x10-6 ± 1,0 x10-6 vs. 1,9 x10- 6 ± 0,5 x10-6, respectivamente) e ao grupo CECBV (p = 0,006) nas regiões: ventral (2,3 x10-6 ± 0,7 x10-7) e dorsal (2,1 x10-6 ± 0,7 x10-6). Edema foi maior no grupo CECC comparado ao Controle nas regiões ventral e dorsal (2,4 x10-2 ± 3,5 x10-2 vs. 8,2 x10-4 ± 0,2 x10-4 e 5,7 x10 -2 ± 4,3 x10-2 vs. 0,3 x10-2 ± 1,0 x10-2, respectivamente, p = 0,016) e mais intenso na região dorsal em todos os grupos (p = 0,004). As IL 10 e IL6 do LBA foram maiores nos grupos submetidos à CECC (41,9 ± 12,2, p = 0,010 e 239,4 ± 45,2, p < 0,001, respectivamente) e à CECBV (40,7 ± 12,0, p = 0,016 e 174,8 ± 61,2, p = 0,004, respectivamente) comparadas ao Controle (21,0 ± 6,9 e 71,8 ± 29,8, respectivamente). As ILs séricas não diferiram entre os grupos (p > 0,05). O Grupo CECC, comparado ao grupo CECBV, mostrou um aumento maior com o tempo na IL6 do LBA (239,4 ± 45,2 vs. 174,8 ± 61,2, p = 0,027, respectivamente) e na IL8 sérica (193,1 ± 108,8 vs. 147,0 ± 59,4, p = 0,040, respectivamente). CONCLUSÕES: Em modelo experimental de circulação extracorpórea em porcos, a manutenção da perfusão e ventilação dos pulmões na CEC biventricular atenua a inflamação pulmonar em comparação à CEC convencional / BACKGROUND: Lung ischemia-reperfusion injury and the membrane oxygenator are considered important factors in the inflammatory response after cardiac surgery and cardiopulmonary bypass (CPB). Previous studies using the own lung as the oxygenator with a biventricular bypass demonstrated the beneficial effects of this technique. However, lung inflammation was not fully evaluated in this scenario. The aim of this study was to observe the impact of the exclusion of the membrane oxygenator and maintenance of lung perfusion on regional lung inflammation in pigs undergoing cardiopulmonary bypass. METHODS: Twenty-seven mechanically ventilated pigs were subjected to a thoracotomy and randomly allocated into Control (n=8), CPB (n=9) or Lung Perfusion (n=10) groups. Animals from the CPB group and Lung Perfusion group were subjected respectively to a conventional CPB or to a biventricular bypass with pulmonary ventilation and perfusion without a membrane oxygenator for 90 minutes. The systemic interleukins (ILs) were determined at baseline, after bypass and 90 min after bypass or at equivalent times in the Control group. ILs from bronchoalveolar lavage fluid (BAL) were evaluated at baseline and 90 min after bypass. Tissue samples were collected from the dorsal and ventral regions of the left lung for assessment of the number of polymorphonuclear leukocytes (PMN) per parenchyma area and edema. Data were evaluated using ANOVA and p< 0.05 was considered significant. RESULTS: The CPB group showed increased lung inflammation, with an increased PMN count compared to the Control (p<0,001) at ventral (2.8 x10-6± 0.7 x10-6 vs. 1.6 x10-6± 0.5 x10-6 , respectively) and dorsal regions (3.3 x10-6 ± 1.0 x10-6 vs. 1.9 x10-6 ± 0.5 x10-6, respectively) and to Lung Perfusion Group (p = 0.006) at ventral (2.3 x10-6 ± 0.7 x10-7) e dorsal regions (2.1 x10-6 ± 0.7 x10-6). Edema was higher in the CPB group compared to the Control at ventral and dorsal regions (2.4 x10-2± 3.5 x10-2 vs. 8.2 x10 -4± 0.2 x10-4 and 5.7 x10 -2 ± 4.3 x10-2 vs. 0.3 x10-2 ± 1.0 x10-2, respectively, p = 0.016) and increased in the dorsal region in all groups (p = 0.004). BAL IL10 and IL6 were higher in groups subjected to CPB group (41.9 ± 12.2, p = 0.010 e 239.4 ± 45.2, p<0.001, respectively) and to Lung Perfusion group (40.7 ± 12.0, p = 0.016 e 174.8 ± 61.2, p = 0.004, respectively) compared to Control group (21.0 ± 6.9 e 71.8 ± 29.8). Systemic interleukins did not differ between groups (p > 0.05). The CPB group compared to Lung Perfusion group showed a higher increase in BAL IL6 (239,4 ± 45,2 vs. 174,8 ± 61,2, p = 0,027, respectively) and in serum IL8 over time (193,1 ± 108,8 vs. 147,0 ± 59,4, p = 0,040, respectively). CONCLUSIONS: In a pig model of extracorporeal circulation, maintenance of lung perfusion and ventilation with biventricular bypass attenuates the pulmonary inflammation as compared to conventional CPB

Nosso objetivo foi determinar que tipo de estatina pode atenuar a lesão pulmonar aguda (LPA) induzida por lipopolissacarídeo (LPS) em camundongos da linhagem C57Bl/6. Trinta camundongos machos ( 23 g) foram divididos em 5 grupos (n=6 cada): grupo LPS (10 mg/kg) administrado intraperitonealmente (i.p.), LPS mais atorvastatina (10 mg/kg/dia; grupo LPS+A), LPS mais pravastatina (5 mg/kg/dia; grupo LPS+P) e LPS mais sinvastatina (20 mg/kg/dia; grupo LPS+S). O grupo controle recebeu salina i.p.. Em um grupo separado de camundongos (n=5), a soma das pressões pulmonares resistivas e viscoelásticas (DeltaPtot) e elastância estática (E[st]) foram medidas. Um dia após a administração de LPS os camundongos foram sacrificados (24 h) por deslocamento cervical e logo em seguida foi realizado lavado broncoalveolar (LBA). Os pulmões foram removidos para análise histopatológica e homogeneizados para análises bioquímicas (ELISA, catalase, superóxido dismutase, mieloperoxidase, substâncias reativas ao ácido tiobarbitúrico, carbonilação de proteínas e método de Griess). A quantidade de leucócitos foi menor no grupo LPS+P (p<0,01) e LPS+S (p<0,05) em comparação ao grupo LPS. Os níveis de MCP-1 e IL-6 reduziram no grupo LPS+P (p<0,01), enquanto o grupo LPS + S mostrou redução apenas nos níveis de IL-6 (p<0,05) em comparação ao grupo LPS. Marcadores redox (superóxido dismutase e catalase) foram menores no grupo LPS+A (p<0,01) em comparação ao grupo LPS. A peroxidação lipídica (malondialdeído e hidroperóxidos) diminuiu em todos os grupos tratados (p<0,05) quando comparados ao grupo LPS. A mieloperoxidase foi menor no grupo LPS+P (p<0,01) quando comparado ao grupo LPS. DeltaPtot e E(st) foram, significativamente, maiores no grupo LPS do que nos outros grupos. Nossos resultados sugerem que atorvastatina e pravastatina, mas não a sinvastatina, exibiram ações anti-inflamatórias e antioxidantes na LPA induzida por LPS. / To determinate what statins could attenuate acute lung injury (ALI) induced by lipopolysaccharide (LPS) in C57BL/6 mice. Young male mice ( 23 g) were divided into 5 groups (n=6 each): injected with LPS i.p. (10 mg/kg), LPS plus atorvastatin (10 mg/kg/day; LPS+A group) or pravastatin (5 mg/kg/day; LPS+P group) or simvastatin (20 mg/kg/day; LPS+S group). Control group received saline (i.p.). In a separated group of mice (n=5) the sum of pulmonary resistive and viscoelastic pressures (DeltaPtot) and static elastance (E[st]) were measured. One day later (24 h), the animals were sacrificed, BAL performed and lungs were removed for histopathological analysis and homogenized for biochemical analyses (ELISA, catalase, superoxide dismutase, myeloperoxidase, thiobarbituric acid reactive substances, protein carbonyls and griess assay). The amount of leukocytes was lower in LPS+P (p<0.01) and LPS+S (p<0.05). Cytokine levels of MCP-1 was lower in LPS+P (p<0.01) while IL-6 was lower in LPS+P (p<0.01) and LPS+S (p <0.05). Redox markers (superoxide dismutase and catalase) were lower in LPS+A (p<0.01). Lipid peroxidation (malondialdehyde and hydroperoxides) were lower in all treated groups (p<0.05). Myeloperoxidase was lower in LPS+P (p<0.01). DeltaPtot and E(st) were significantly higher in the LPS group than in the other groups. Our results suggest that atorvastatin and pravastatin, but no simvastatin, exhibits anti-inflammatory and antioxidant actions in LPS-induced ALI.

Introdução: A ventilação manual é um aspecto chave que determina a eficiência da ressuscitação neonatal e pode ser realizada por várias categorias de profissionais utilizando diferentes equipamentos. Objetivos: Comparar os efeitos da ventilação manual realizada por diferentes profissionais envolvidos na assistência neonatal, médicos, enfermeiros e fisioterapeutas, utilizando dois equipamentos: Peça T e balão autoinflável. Métodos: Coelhos adultos foram submetidos à ventilação manual utilizando Peça T ou balão autoinflável, 10 minutos com cada dispositivo, operado por médicos, fisioterapeutas e enfermeiros, num total de 21 indivíduos. A escolha do primeiro dispositivo utilizado por cada voluntário foi realizada por randomização. Os dados de mecânica respiratória (volume corrente, volume minuto, frequência respiratória, tempos inspiratório e expiratório, pressão inspiratória e pressão expiratória final positiva) foram obtidos de maneira contínua através de um sistema informatizado de aquisição de dados, cega para os operadores. Amostras de sangue arterial foram obtidas por cateterização da carótida antes e depois de cada ventilação manual para determinação da PaCO2 e do pH. Foram comparados os dispositivos entre si, assim como o desempenho dos grupos de profissionais com cada dispositivo. Resultados: Quando analisados todos os profissionais em conjunto (n = 21) os animais ventilados com o balão autoinflável apresentaram maior volume minuto, menor frequência respiratória, menor tempo inspiratório e maiores valores de pH após o período de 10 minutos de ventilação. Quando analisados separadamente cada um dos três grupos de profissionais, os animais ventilados com o balão autoinflável no grupo Enfermeiras (n = 7) apresentaram maior volume minuto (390±108 vs 766±410 mL/min, p < 0,05) em relação ao grupo Fisioterapeutas (n = 7) (418±192 vs 886±787 mL/min) e grupo Médicos (n = 7) (438±206 vs 705±434 mL/min). Resultados similares foram encontrados em relação ao pH após 10 minutos de ventilação manual, sendo observada no grupo Enfermeiras a ocorrência de alcalose respiratória (7,40±0,11 vs 7,61±0,02, p < 0,05, 7,37±0,10 vs 7,52±0,23, 7,36±0,07 vs 7,40±0,18 mL/min, respectivamente) e de hipocapnia (32,4±6,9 vs 23,4±7,5 mmHg, p < 0,05; 40,4±10,8 vs 28,0±15,2 mmHg, 38,0±13,8 vs 42,6±18,1 mmHg) respectivamente. Conclusão: O balão autoinflável resultou em hipocapnia e alcalose respiratória no grupo Enfermeiras, a ventilação manual utilizando a Peça T resultou em menor volume corrente e menor volume minuto / Introduction: Manual ventilation is a key aspect that determines the efficiency of neonatal resuscitation and can be performed by several categories of professionals using different equipment. Objectives: To compare the effects of manual ventilation performed by different professionals involved in neonatal care, physicians, nurses and physiotherapists, using two devices: T-piece and self-inflating bag. Methods: Adult rabbits were submitted to manual ventilation using T-piece or self-inflating bag, 10 minutes with each device, operated by physicians, physiotherapists and nurses, in a total of 21 individuals. The choice of the first device used by each volunteer was by randomization. Respiratory mechanics data (tidal volume, minute volume, respiratory rate, inspiratory and expiratory time, inspiratory pressure and positive end expiratory pressure) were obtained continuously through a computerized data acquisition system, blind to operators. Arterial blood gas samples were obtained through carotid catheterization before and after each manual ventilation for determination of PaCO2 and pH. The devices were compared to each other as well as the performance of groups of professionals with each device. Results: When all the professionals (n = 21) were analyzed together, the animals ventilated with the self-inflating bag presented higher minute volume, lower respiratory rate, shorter inspiratory time and higher pH values after 10 minutes of ventilation. When the three groups of professionals were analyzed separately, the animals ventilated with the self-inflating bag in the Nurse group (n = 7) had a higher minute volume (390±108 vs 766±410 mL/min, p < 0.05) compared to the Physiotherapists group (n = 7) (418±192 vs 886±787 mL/min) and the Physicians group (n = 7) (438±206 vs. 705±434 mL/min). Similar results were found in relation to pH after 10 minutes of manual ventilation, with the occurrence in the Nurses group of respiratory alkalosis (7.40±0.11 vs 7.61±0.02, p < 0.05, 7.37±0.10 vs 7.52±0.23, 7.36±0.07 vs 7.40±0.18 mL/min, respectively) and hypocapnia (32.4±6.9 vs 23.4±7.5 mmHg, p < 0.05; 40.4±10.8 vs 28.0 ± 15.2 mmHg, 38.0±13.8 vs. 42.6±18.1 mmHg) respectively. Conclusion: The self-inflating bag resulted in hypocapnia and respiratory alkalosis in the Nurses group, manual ventilation using T-piece resulted in lower tidal volume and minute volume

In many parts of the world, civilians and peacekeepers are exposed to potentially serious injury from blasts and explosions. Providing insight into the trauma thresholds for blast injury is necessary for the development of blast protection equipment and identification and subsequent treatment of blast injury. [Phillips, 1988] Blast injury can be categorized as primary, secondary, tertiary, quaternary and quinernary, corresponding to different aspects of the blast loading and injury mechanisms. Primary blast injury occurring in the lungs is of importance, since lung injury results in one of the highest rate of blast mortality. Much of the existing blast injury data was obtained from animal testing with sheep and subsequently extrapolated to humans using scaling techniques. More recently, mathematical, experimental and numerical models have been developed and employed to investigate blast injury. In this study, a detailed finite element model of a sheep thorax and human thorax (developed at the University of Waterloo) was used to predict primary blast lung injury based on a range of blast loading conditions. The models were developed based on available anatomical data and material properties to model the organs and tissues, and were evaluated using the LS-Dyna explicit finite element code. The models were previously validated for the prediction of lung PBI using Friedlander-type blast waves. All results were compared to existing literature to further verify and validate the numerical models as wells as to provide insight on the effect of loading conditions on blast injury. The blast loading input for these simulations used idealized blast waves, based on a blast physics approach. Blast loads were verified using the Chinook CFD software. The effects of idealized blast waves on predicted lung injury were investigated to determine the importance of peak pressure, blast wave duration and impulse. The duration and peak pressures for the waves were selected based on the Bowen and UVa curves, and included a right angle triangular shape and a square wave to allow for the different parameters to be considered. These results were compared to the Bowen and revised Bowen injury models. The results show that the peak overpressure is dominant in predicting injury for blast loads with long durations (>8 ms). The impulse was dominant in predicting injury for blast loads with short durations (<1 ms). For blasts loads with intermediate durations (1 ms < 8 ms) both the shape of the blast load wave and peak overpressure play a role in primary blast lung injury. The effect of orientation of the body position on primary blast lung injury was investigated. Simulations were performed using the sheep and human numerical models along with a model of a commonly used experimental device, the Blast Test Device (BTD) cylinder. These models were oriented in different positions by rotating the body relative to the blast flow. Injury results for the BTD were calculated using the Injury 8.1 injury prediction software. The BTD simulations served several purposes; it was used as a reference for the human and sheep simulations and its effectiveness as a tool to predict body orientation was evaluated. In general, all of the models predicted appropriate and similar levels of injury for the body in its default orientation, and these predictions were comparable to the accepted injury levels for this insult. For other orientations the BTD was not able to predict the appropriate blast injury. This highlighted the importance of proper placement and orientation of the BTD when used in simulations or physical experiments. The overall injury (based on the results from the right and left lung) predicted by the sheep and human thorax was similar for all orientations. However, very different results were obtained when the predicted injury for the right and left lungs was compared. The differences between the sheep and the human were examined and the differences in injury between the right and left lung is a result of the differences in anatomy between the two species. This study has evaluated the importance of blast wave parameters in predicting primary blast injury, an important consideration for the improvement of blast protection, and the effect of body orientation on primary blast injury, an important consideration for experimental testing and a starting point for the evaluation of complex blast loading. Future work will focus on the evaluation of injury in complex blast environments.

Concerns exist regarding the ability of HFOV to provide the needed lung protective ventilation for adult patients with ARDS. HFOV is increasingly being used as a lung protecting ventilation mode even if some of its protective attributes may be lost as the airway resistance (Raw) increases or decreases. In fact, in cases of shifting air resistance, HFOV may have caused lung injury. PURPOSE: The purpose of this study was to investigate the effect of airway resistance on tidal volume (Vt) delivered by HFOV to adult patients. Also, the study intended to determine direction for volume change when resistance increases or decreases. METHODS: An in vitro model was used to simulate an adult passive patient with ARDS using a breathing simulator (Active Servo Lung 5000, Ingmar Medical, Pittsburgh, PA, USA). Adjustable resistance and compliance for each lung was used. The resistance levels of 15, 30, 45 (cm H2O/L/sec) were used for upper and lower Raw and CL was fixed at 40 mL/cm H2O. The ventilator (Sensormedics 3100B) was set to MAP = 35 cm H2O, to insp-time of 33%, to bias flow =30 L/min, to delta-P of 80, and to 50% oxygen. Vt was recorded (n=3) for each Raw, and the data was collected on the host computer. Approximately 200-250 breaths of data for each Raw were captured via the ASL software and then converted to Excel for analysis. An average of 80 breathes (following the steady Vt level) was used in each analysis. DATA ANALYSIS: The data analysis was performed with one way ANOVA and with a post hoc Bonferroni test in order to determine the statistical significance of the delivered Vt with each Raw. A probability of (p < 0.05) was accepted as statistically significant. RESULTS: The descriptive statistics of the average delivered Vt with regard to each Raw (15, 30, 45 cm H2O/L/sec) were the number of experiments (n=3), mean Vt (93.52, 89.09, 85.99 mL), and standard deviations (SD) (1.38, 1.11, 1.10) respectively. There was an inverse relationship between tidal volume and airway resistance during HFOV. With all other variables kept constant, higher resistance caused less volume, whereas lower resistance caused more volume. The one-way ANOVA test showed that there were significant differences between the delivered tidal volumes. When the post hoc Bonferroni test was used, the data showed significant differences between airway resistances of 15 cm H2O/L/sec and 30 cm H2O/L/sec and between 15 cm H2O/L/sec and 45 cm H2O/L/sec. In contrast, no significant differences were found between airway resistances of 30 cm H2O/L/sec and 45 cm H2O/L/sec. CONCLUSION: Vt is not constant during HFOV. Airway resistance is one of the determinants of delivered tidal volume in adults with ARDS during HFOV. Airway resistance should be an important factor in ventilator management and in clinical experiments of patients on HFOV. Without a proper Vt measurement device HFOV should not be used as lung protective ventilation for adult patients with ARDS.

In many parts of the world, civilians and peacekeepers are exposed to potentially serious injury from blasts and explosions. Providing insight into the trauma thresholds for blast injury is necessary for the development of blast protection equipment and identification and subsequent treatment of blast injury. [Phillips, 1988] Blast injury can be categorized as primary, secondary, tertiary, quaternary and quinernary, corresponding to different aspects of the blast loading and injury mechanisms. Primary blast injury occurring in the lungs is of importance, since lung injury results in one of the highest rate of blast mortality. Much of the existing blast injury data was obtained from animal testing with sheep and subsequently extrapolated to humans using scaling techniques. More recently, mathematical, experimental and numerical models have been developed and employed to investigate blast injury. In this study, a detailed finite element model of a sheep thorax and human thorax (developed at the University of Waterloo) was used to predict primary blast lung injury based on a range of blast loading conditions. The models were developed based on available anatomical data and material properties to model the organs and tissues, and were evaluated using the LS-Dyna explicit finite element code. The models were previously validated for the prediction of lung PBI using Friedlander-type blast waves. All results were compared to existing literature to further verify and validate the numerical models as wells as to provide insight on the effect of loading conditions on blast injury. The blast loading input for these simulations used idealized blast waves, based on a blast physics approach. Blast loads were verified using the Chinook CFD software. The effects of idealized blast waves on predicted lung injury were investigated to determine the importance of peak pressure, blast wave duration and impulse. The duration and peak pressures for the waves were selected based on the Bowen and UVa curves, and included a right angle triangular shape and a square wave to allow for the different parameters to be considered. These results were compared to the Bowen and revised Bowen injury models. The results show that the peak overpressure is dominant in predicting injury for blast loads with long durations (>8 ms). The impulse was dominant in predicting injury for blast loads with short durations (<1 ms). For blasts loads with intermediate durations (1 ms < 8 ms) both the shape of the blast load wave and peak overpressure play a role in primary blast lung injury. The effect of orientation of the body position on primary blast lung injury was investigated. Simulations were performed using the sheep and human numerical models along with a model of a commonly used experimental device, the Blast Test Device (BTD) cylinder. These models were oriented in different positions by rotating the body relative to the blast flow. Injury results for the BTD were calculated using the Injury 8.1 injury prediction software. The BTD simulations served several purposes; it was used as a reference for the human and sheep simulations and its effectiveness as a tool to predict body orientation was evaluated. In general, all of the models predicted appropriate and similar levels of injury for the body in its default orientation, and these predictions were comparable to the accepted injury levels for this insult. For other orientations the BTD was not able to predict the appropriate blast injury. This highlighted the importance of proper placement and orientation of the BTD when used in simulations or physical experiments. The overall injury (based on the results from the right and left lung) predicted by the sheep and human thorax was similar for all orientations. However, very different results were obtained when the predicted injury for the right and left lungs was compared. The differences between the sheep and the human were examined and the differences in injury between the right and left lung is a result of the differences in anatomy between the two species. This study has evaluated the importance of blast wave parameters in predicting primary blast injury, an important consideration for the improvement of blast protection, and the effect of body orientation on primary blast injury, an important consideration for experimental testing and a starting point for the evaluation of complex blast loading. Future work will focus on the evaluation of injury in complex blast environments.

No description available.

Acute lung injury (ALI) is a major cause of mortality after lung transplantation. Recent studies indicate protein kinase C delta (PKCδ) could be an effective target to treat ALI. We have developed a gold nanoparticle (GNP)-peptide hybrid that can inhibit PKCδ signaling. PKCδ inhibitor peptide (PKCi) and 95P2P4 stabilizing peptides were conjugated onto GNP. Physicochemical properties of the nanoformulations were examined. A lung transplant-simulated cell culture model was used to evaluate therapeutic efficacy in vitro. A pulmonary ischemia-reperfusion (IR) model was used to test therapeutic efficacy in vivo. GNP-Peptide hybrids showed good stability with high cellular uptake. GNP-PKCi formulations demonstrated anti-inflammatory and anti-apoptotic effects in vitro. When administered to rats under IR stress, GNP-PKCi formulation improved blood oxygenation, reduced pulmonary edema and histological lung injury. In conclusion, we have successfully formulated a clinically-applicable nanoparticle with therapeutic potential to ameliorate lung injury and inflammation. Our formulation strategy could be used to deliver other peptide-based drugs.