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Modulação da pressão intracraniana em um modelo experimental de hipertensão abdominal e lesão pulmonar aguda; Factors associated with variation in intracranial pressure in a model of intra-abdominal hypertension with acute lung injury

ZAMPIERI, Fernando Godinho; ALMEIDA, Juliana Roberta; SCHETTINO, Guilherme Pinto de Paula; PARK, Marcelo; MACHADO, Fabio Santana; AZEVEDO, Luciano Cesar Pontes
Fonte: Associação de Medicina Intensiva Brasileira - AMIB Publicador: Associação de Medicina Intensiva Brasileira - AMIB
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
66.27%
OBJETIVO: Avaliar o efeito de alterações hemodinâmicas, respiratórias e metabólicas sobre a pressão intracraniana em um modelo de lesão pulmonar aguda e síndrome compartimental abdominal. MÉTODOS: Oito porcos Agroceres foram submetidos, após a instrumentação, a cinco cenários clínicos: 1) estado basal com baixa pressão intra-abdominal e pulmão sadio; 2) pneumoperitôneo, com pressão intra-abdominal de 20 mm Hg; 3) lesão pulmonar aguda induzida por lavagem pulmonar e desativação de surfactante; 4) pneumoperitôneo com pressão intra-abdominal de 20 mm Hg na vigência de lesão pulmonar aguda e com PEEP baixo; e 5) PEEP ajustado a 27 cm H2O na vigência de pneumoperitôneo e lesão pulmonar aguda. Variáveis respiratórias e hemodinâmicas foram coletadas. Análise multivariada foi realizada buscando as variáveis associadas com elevação da pressão intracraniana nos cinco cenários estudados. RESULTADOS: Após a análise multivariada, nas situações não associadas com lesão pulmonar aguda apenas a pressão de platô das vias aéreas se correlacionou positivamente com a pressão intracraniana. Nos modelos associados com lesão pulmonar aguda, a pressão de platô de vias aéreas, a pressão arterial de CO2, o CO2 no final da expiração e a pressão venosa central se correlacionaram positivamente com incrementos da pressão intracraniana. CONCLUSÃO: Em um modelo de disfunção orgânica múltipla com situações clínicas associadas com aumento da pressão torácica e abdominal...

Impact of pressure profile and duration of recruitment maneuvers on morphofunctional and biochemical variables in experimental lung injury

SILVA, Pedro L.; MORAES, Lillian; SANTOS, Raquel S.; SAMARY, Cynthia; ORNELLAS, Debora S.; MARON-GUTIERREZ, Tatiana; MORALES, Marcelo M.; SADDY, Felipe; CAPELOZZI, Vera L.; PELOSI, Paolo; MARINI, John J.; ABREU, Marcelo Gama de; ROCCO, Patricia R. M.
Fonte: LIPPINCOTT WILLIAMS & WILKINS Publicador: LIPPINCOTT WILLIAMS & WILKINS
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
66.27%
Objective: To investigate the effects of the rate of airway pressure increase and duration of recruitment maneuvers on lung function and activation of inflammation, fibrogenesis, and apoptosis in experimental acute lung injury. Design: Prospective, randomized, controlled experimental study. Setting: University research laboratory. Subjects: Thirty-five Wistar rats submitted to acute lung injury induced by cecal ligation and puncture. Interventions: After 48 hrs, animals were randomly distributed into five groups (seven animals each): 1) nonrecruited (NR); 2) recruitment maneuvers (RMs) with continuous positive airway pressure (CPAP) for 15 secs (CPAP15); 3) RMs with CPAP for 30 secs (CPAP30); 4) RMs with stepwise increase in airway pressure (STEP) to targeted maximum within 15 secs (STEP15); and 5) RMs with STEP within 30 secs (STEP30). To perform STEP RMs, the ventilator was switched to a CPAP mode and positive end-expiratory pressure level was increased stepwise. At each step, airway pressure was held constant. RMs were targeted to 30 cm H(2)O. Animals were then ventilated for 1 hr with tidal volume of 6 mL/kg and positive end-expiratory pressure of 5 cm H(2)O. Measurements and Main Results: Blood gases, lung mechanics, histology (light and electronic microscopy)...

Recruitment maneuver in experimental acute lung injury: The role of alveolar collapse and edema

SANTIAGO, Viviane R.; RZEZINSKI, Andreia F.; NARDELLI, Liliane M.; SILVA, Johnatas D.; GARCIA, Cristiane S. N. B.; MARON-GUTIERREZ, Tatiana; ORNELLAS, Debora S.; MORALES, Marcelo M.; CAPELOZZI, Vera L.; MARINI, John; PELOSI, Paolo; ROCCO, Patricia R. M.
Fonte: LIPPINCOTT WILLIAMS & WILKINS Publicador: LIPPINCOTT WILLIAMS & WILKINS
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
66.41%
Objective: In acute lung injury, recruitment maneuvers have been used to open collapsed lungs and set positive end-expiratory pressure, but their effectiveness may depend on the degree of lung injury. This study uses a single experimental model with different degrees of lung injury and tests the hypothesis that recruitment maneuvers may have beneficial or deleterious effects depending on the severity of acute lung injury. We speculated that recruitment maneuvers may worsen lung mechanical stress in the presence of alveolar edema. Design: Prospective, randomized, controlled experimental study. Setting: University research laboratory. Subjects: Thirty-six Wistar rats randomly divided into three groups (n = 12 per group). Interventions: In the control group, saline was intraperitoneally injected, whereas moderate and severe acute lung injury animals received paraquat intraperitoneally (20 mg/kg [moderate acute lung injury] and 25 mg/kg [severe acute lung injury]). After 24 hrs, animals were further randomized into subgroups (n = 6/each) to be recruited (recruitment maneuvers: 40 cm H(2)O continuous positive airway pressure for 40 secs) or not, followed by 1 hr of protective mechanical ventilation (tidal volume, 6 mL/kg; positive end-expiratory pressure...

Degree of endothelium injury promotes fibroelastogenesis in experimental acute lung injury

CHAO, Monica C. M.; GARCIA, Cristiane S. N. B.; OLIVEIRA, Mariana B. G. de; SANTOS, Raquel S.; LUCAS, Isabela H.; SILVA, Pedro L.; VIEIRA-ABREU, Adriana; CASTRO-FARIA-NETO, Hugo C. de; PARRA-CUENTAS, Edwin R.; CAPELOZZI, Vera L.; PELOSI, Paolo; ROCCO, Pat
Fonte: ELSEVIER SCIENCE BV Publicador: ELSEVIER SCIENCE BV
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
66.26%
We tested the hypothesis that at the early phase of acute lung injury (ALI) the degree of endothelium injury may predict lung parenchyma remodelling For this purpose, two models of extrapulmonary ALI induced by Escherichia col: lipopolysaccharide (ALI-LPS) or cecal ligation and puncture (ALI-CLP) were developed in mice At day 1, these models had similar degrees of lung mechanical compromise, epithelial damage, and intraperitoneal inflammation, but endothelial lesion was greater in ALI-CLP A time course analysis revealed, at day 7 ALI-CLP had higher degrees of epithelial lesion, denudation of basement membrane, endothelial damage, elastic and collagen fibre content, neutrophils in bronchoalveolar lavage fluid (BALF), peritoneal fluid and blood, levels of interleukin-6, KC (murine analogue of IL-8), and transforming growth factor-beta in BALF Conversely, the number of lung apoptotic cells was similar in both groups In conclusion, the intensity of fibroelastogenesis was affected by endothelium injury in addition to the maintenance of epithelial damage and intraperitoneal inflammation. (C) 2010 Elsevier B V All rights reserved; Centres of Excellence Program (PRONEX-FAPERJ); Brazilian Council for Scientific and Technological Development (CNPq); Rio de Janeiro State Research Supporting Foundation (FAPERJ); Coordination for the Improvement of Higher Education Personnel (CAPES); Sao Paulo State Research Supporting Foundation (FAPESP)

Assisted ventilation modes reduce the expression of lung inflammatory and fibrogenic mediators in a model of mild acute lung injury

SADDY, Felipe; OLIVEIRA, Gisele P.; GARCIA, Cristiane S. N. B.; NARDELLI, Liliane M.; RZEZINSKI, Andreia F.; ORNELLAS, Debora S.; MORALES, Marcelo M.; CAPELOZZI, Vera L.; PELOSI, Paolo; ROCCO, Patricia R. M.
Fonte: SPRINGER Publicador: SPRINGER
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
66.29%
The goal of the study was to compare the effects of different assisted ventilation modes with pressure controlled ventilation (PCV) on lung histology, arterial blood gases, inflammatory and fibrogenic mediators in experimental acute lung injury (ALI). Paraquat-induced ALI rats were studied. At 24 h, animals were anaesthetised and further randomized as follows (n = 6/group): (1) pressure controlled ventilation mode (PCV) with tidal volume (V (T)) = 6 ml/kg and inspiratory to expiratory ratio (I:E) = 1:2; (2) three assisted ventilation modes: (a) assist-pressure controlled ventilation (APCV1:2) with I:E = 1:2, (b) APCV1:1 with I:E = 1:1; and (c) biphasic positive airway pressure and pressure support ventilation (BiVent + PSV), and (3) spontaneous breathing without PEEP in air. PCV, APCV1:1, and APCV1:2 were set with P (insp) = 10 cmH(2)O and PEEP = 5 cmH(2)O. BiVent + PSV was set with two levels of CPAP [inspiratory pressure (P (High) = 10 cmH(2)O) and positive end-expiratory pressure (P (Low) = 5 cmH(2)O)] and inspiratory/expiratory times: T (High) = 0.3 s and T (Low) = 0.3 s. PSV was set as follows: 2 cmH(2)O above P (High) and 7 cmH(2)O above P (Low). All rats were mechanically ventilated in air and PEEP = 5 cmH(2)O for 1 h. Assisted ventilation modes led to better functional improvement and less lung injury compared to PCV. APCV1:1 and BiVent + PSV presented similar oxygenation levels...

Bradykinin inducible receptor is essential to lipopolysaccharide-induced acute lung injury in mice

CAMPANHOLLE, Gabriela; LANDGRAF, Richardt G.; BORDUCCHI, Erica; SEMEDO, Patricia; WANG, Pamela H. M.; AMANO, Mariane T.; RUSSO, Momtchilo; PACHECO-SILVA, Alvaro; JANCAR, Sonia; CAMARA, Niels O. S.
Fonte: ELSEVIER SCIENCE BV Publicador: ELSEVIER SCIENCE BV
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
66.27%
Lipopolysaccharides from gram-negative bacteria are amongst the most common causative agents of acute lung injury, which is characterized by an inflammatory response, with cellular infiltration and the release of mediators/cytokines. There is evidence that bradykinin plays a role in lung inflammation in asthma but in other types of lung inflammation its role is less clear. In the present study we evaluated the role of the bradykinin B(1) receptor in acute lung injury caused by lipopolysaccharide inhalation and the mechanisms behind bradykinin actions participating in the inflammatory response. We found that in C57BI/6 mice, the bradykinin B(1) receptor expression was up-regulated 24 h after lipopolysaccharide inhalation. At this time, the number of cells and protein concentration were significantly increased in the bronchoalveolar lavage fluid and the mice developed airway hyperreactivity to methacholine. In addition, there was an increased expression of tumor necrosis factor-alpha, interleukin-1 beta and interferon-gamma and chemokines (monocytes chemotactic protein-1 and KC) in the bronchoalveolar lavage fluid and in the lung tissue. We then treated the mice with a bradykinin B, receptor antagonist, R-954 (Ac-Orn-[Oic(2), alpha-MePhe(5)...

Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases inflammation in a murine model of acute lung injury: Role for the adenosine A(2A) receptor

Ribeiro, Alison; Ferraz-de-Paula, Viviane; Pinheiro, Milena L.; Vitoretti, Luana B.; Mariano-Souza, Domenica P.; Quinteiro-Filho, Wanderley M.; Akamine, Adriana T.; Almeida, Vinicius I.; Quevedo, Joao; Dal-Pizzol, Felipe; Hallak, Jaime E.; Zuardi, Antonio
Fonte: ELSEVIER SCIENCE BV; AMSTERDAM Publicador: ELSEVIER SCIENCE BV; AMSTERDAM
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
66.31%
Acute lung injury is an inflammatory condition for which treatment is mainly supportive because effective therapies have not been developed. Cannabidiol, a non-psychotropic cannabinoid component of marijuana (Cannabis sativa), has potent immunosuppressive and anti-inflammatory properties. Therefore, we investigated the possible anti-inflammatory effect of cannabidiol in a murine model of acute lung injury. Analysis of total inflammatory cells and differential in bronchoalveolar lavage fluid was used to characterize leukocyte migration into the lungs; myeloperoxidase activity of lung tissue and albumin concentration in the bronchoalveolar lavage fluid were analyzed by colorimetric assays; cytokine/chemokine production in the bronchoalveolar lavage fluid was also analyzed by Cytometric Bead Arrays and Enzyme-Linked Immunosorbent Assay (ELISA). A single dose of cannabidiol (20 mg/kg) administered prior to the induction of LPS (lipopolysaccharide)-induced acute lung injury decreases leukocyte (specifically neutrophil) migration into the lungs, albumin concentration in the bronchoalveolar lavage fluid, myeloperoxidase activity in the lung tissue, and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) 1...

Estudo da incidência de lesão pulmonar aguda e síndrome do desconforto respiratório agudo nas unidades de terapia intensiva da região da Grande Vitória no Espírito Santo; Study of the incidence of acute lung injury and acute respiratory distress syndrome in the intensive care units in the region of Vitória in Espírito Santo

Caser, Eliana Bernadete
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 21/02/2013 Português
Relevância na Pesquisa
66.27%
INTRODUÇÃO: Existem muitas controvérsias, nos estudos epidemiológicos existentes, a respeito da incidência e desfechos da síndrome de lesão pulmonar aguda. A incidência e as características clínicas da síndrome dependem principalmente da definição utilizada e da metodologia empregada no estudo, bem como da disponibilização e utilização dos leitos nas unidades de terapia intensiva da região estudada. Pela ausência de dados epidemiológicos existentes de lesão pulmonar aguda na Grande Vitória, no Espírito Santo, realizamos este estudo para analisar a incidência, características, sobrevida aos 28 dias e mortalidade hospitalar. MÉTODOS: Os pacientes internados nas 14 unidades de terapia intensiva da Grande Vitória, durante o período de 15 meses, submetidos à ventilação mecânica e que preencheram os critérios de lesão pulmonar aguda da Conferência de Consenso Européia-Americana de 1994 foram selecionados prospectivamente para o estudo. Os pacientes também foram classificados de acordo com a nova definição de Berlim. Avaliamos as características clínicas e funcionais no primeiro dia de internação, durante a primeira semana, no 14º dia e no 28º dia de evolução. Foram calculadas a incidência da síndrome acumulada/ano...

Effects of Inhaled Nitric Oxide on Oxidative Stress and Histopathological and Inflammatory Lung Injury in a Saline-Lavaged Rabbit Model of Acute Lung Injury

Fioretto, Jose R.; Campos, Fabio J.; Ronchi, Carlos F.; Ferreira, Ana L. A.; Kurokawa, Cilmery S.; Carpi, Mario F.; Moraes, Marcos A.; Bonatto, Rossano C.; Defaveri, Julio; Yeum, Kyung-Jin
Fonte: Daedalus Enterprises Inc Publicador: Daedalus Enterprises Inc
Tipo: Artigo de Revista Científica Formato: 273-281
Português
Relevância na Pesquisa
66.35%
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Processo FAPESP: 07/03173-2; BACKGROUND: Conventional mechanical ventilation (CMV) is fundamental in acute respiratory distress syndrome (ARDS) treatment. Inhaled nitric oxide (INO), an adjunctive therapy, has been used with ventilation in an attempt to improve oxygenation and reduce lung injury. OBJECTIVE: To analyze the early effects of low INO dose on oxygenation, oxidative stress, inflammatory, and histopathological lung injury in a rabbit model of acute lung injury (ALI). METHODS: This was a prospective, controlled, in vivo animal laboratory study. Forty rabbits were instrumented and ventilated at F-IO2 1.0. ALI was induced by tracheal infusion of warm saline (30 mL/kg, 38 degrees C) and lung oxidative stress was assessed by total antioxidant performance (TAP) assay. Animals were assigned to groups: control group (no. = 10, low tidal volume [V-T] = 6 mL/kg, PEEP = 5 cm 1120), ALI without INO (no-INO group, no. = 10, low V-T = 6 mL/kg, PEEP = 10 cm H2O), ALI plus INO (INO group, no. = 10, low V-T = 6 mL/kg, PEEP = 10 cm H2O, INO = 5 ppm). Plateau pressure was limited to 30 cm H2O in all groups. Ten non-instrumented animals (healthy group) were studied for TAP assay. Ventilatory and hemodynamic parameters were recorded every 30 min for 4 hours. RESULTS: After lung injury...

High-frequency oscillatory ventilation attenuates oxidative lung injury in a rabbit model of acute lung injury

Ronchi, Carlos Fernando; dos Anjos Ferreira, Ana Lucia; Campos, Fabio Joly; Kurokawa, Cilmery Suemi; Carpi, Mario Ferreira; de Moraes, Marcos Aurelio; Bonatto, Rossano Cesar; Defaveri, Julio; Yeum, Kyung-Jin; Fioretto, Jose Roberto
Fonte: Royal Soc Medicine Press Ltd Publicador: Royal Soc Medicine Press Ltd
Tipo: Artigo de Revista Científica Formato: 1188-1196
Português
Relevância na Pesquisa
66.35%
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Processo FAPESP: 08/08199-2; Mechanical ventilation (MV) can induce lung oxidative stress, which plays an important role in pulmonary injury. This study compared protective conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation (HFOV) for oxygenation, oxidative stress, inflammatory and histopathological lung injury in a rabbit model of acute lung injury (ALI). Rabbits (n = 30) were ventilated at FiO(2) 1.0. Lung injury was induced by tracheal saline infusion (30 mL/kg, 38 degrees C). Animals were randomly assigned to: (a) sham control (CG: tidal volume [V(T)] 6 mL/kg, positive end expiratory pressure [PEEP] 5 cmH(2)O, respiratory rate [RR] 40 ipm); (b) ALI + CMV (CMVG: V(T) 6 mL/kg, PEEP 10 cmH(2)O, RR 40 ipm); or (c) ALI + HFOV (HFG: mean airway pressure [Paw] 14 cmH(2)O, RR 10 Hz) groups. Lung oxidative stress was assessed by total antioxidant performance assay, inflammatory response by the number of polymorphonuclear leukocytes/bronchoalveolar lavage fluid/lung and pulmonary histological damage was quantified by a score. Ventilatory and hemodynamic parameters were recorded every 30 min. Both ALI groups showed worse oxygenation after lung injury induction. After four hours of ventilation...

Effects of contrast material on computed tomographic measurements of lung volumes in patients with acute lung injury

Bouhemad, Bélaid; Puybasset, L.; Coriat, P.; Roussat, M. O.; Goldstein, I.; Nieszkowska, A.; Richecoeur, Jack; Lu, Qin; Malbouisson, Luiz M.; Cluzel, Philippe; Rouby, Jean-Jacques; Gusman, P.; Vieira, S.; Elman, M.
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 63-71
Português
Relevância na Pesquisa
66.3%
Background. Intravenous injection of contrast material is routinely performed in order to differentiate nonaerated lung parenchyma from pleural effusion in critically ill patients undergoing thoracic computed tomography (CT). The aim of the present study was to evaluate the effects of contrast material on CT measurement of lung volumes in 14 patients with acute lung injury. Method. A spiral thoracic CT scan, consisting of contiguous axial sections of 10 mm thickness, was performed from the apex to the diaphragm at end-expiration both before and 30 s (group 1; n=7) or 15 min (group 2; n=7) after injection of 80 ml contrast material. Volumes of gas and tissue, and volumic distribution of CT attenuations were measured before and after injection using specially designed software (Lungview®; Institut National des Télécommunications, Evry, France). The maximal artifactual increase in lung tissue resulting from a hypothetical leakage within the lung of the 80 ml contrast material was calculated. Results. Injection of contrast material significantly increased the apparent volume of lung tissue by 83 ± 57 ml in group 1 and 102 ± 80 ml in group 2, whereas the corresponding maximal artifactual increases in lung tissue were 42 ± 52 ml and 31 ± 18 ml. Conclusion. Because systematic injection of contrast material increases the amount of extravascular lung water in patients with acute lung injury...

Role of gelatinases MMP-2 and MMP-9 in tissue remodeling following acute lung injury

Corbel,M.; Boichot,E.; Lagente,V.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/07/2000 Português
Relevância na Pesquisa
66.26%
Acute lung injury is characterized by a severe disruption of alveolo-capillary structures and includes a variety of changes in lung cell populations. Evidence suggests the occurrence of rupture of the basement membranes and interstitial matrix remodeling during acute lung injury. The dynamic equilibrium of the extracellular matrix (ECM) under physiological conditions is a consequence of the balance between the regulation of synthesis and degradation of ECM components. Matrix metalloproteinases (MMPs) represent a group of enzymes involved in the degradation of most of the components of the ECM and therefore participate in tissue remodeling associated with pathological situations such as acute lung injury. MMP activity is regulated by proteolytic activation of the latent secreted proenzyme and by interaction with specific tissue inhibitors of metalloproteinases. This review details our knowledge of the involvement of MMPs, namely MMP-2 and MMP-9, in acute lung injury and acute respiratory distress syndrome.

Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

Bakkal,B.H.; Gultekin,F.A.; Guven,B.; Turkcu,U.O.; Bektas,S.; Can,M.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/09/2013 Português
Relevância na Pesquisa
66.29%
Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels...

Mechanisms and Modification of Chlorine-induced Lung Injury in Animals

Yadav, Amit K.; Bracher, Andreas; Doran, Stephen F.; Leustik, Martin; Squadrito, Giuseppe L.; Postlethwait, Edward M.; Matalon, Sadis
Fonte: American Thoracic Society Publicador: American Thoracic Society
Tipo: Artigo de Revista Científica
Publicado em 01/07/2010 Português
Relevância na Pesquisa
66.26%
Chlorine (Cl2) is a reactive oxidant gas used extensively in industrial processes. Exposure of both humans and animals to high concentrations of Cl2 results in acute lung injury, which may resolve spontaneously or progress to acute respiratory failure. Injury to airway and alveolar epithelium may result from chemical reactions of Cl2, from HOCl (the hydrolysis product of Cl2), and/or from the various reaction products, such as chloramines, that are formed from the reactions of these chlorinating species with biological molecules. Subsequent reactions may initiate self-propagating reactions and induce the production of inflammatory mediators compounding injury to pulmonary surfactant, ion channels, and components of lung epithelial and airway cells. Low-molecular-weight antioxidants, such as ascorbate, glutathione, and urate, present in the lung epithelial lining fluid and tissue, remove Cl2 and HOCl and thus decrease injury to critical target biological targets. However, levels of lung antioxidants of animals exposed to Cl2 in concentrations likely to be encountered in the vicinity of industrial accidents decrease rapidly and irreversibly. Our measurements show that prophylactic administration of a mixture containing ascorbate and desferal N-acetyl-cysteine...

Functional Genomics of Chlorine-induced Acute Lung Injury in Mice

Leikauf, George D; Pope-Varsalona, Hannah; Concel, Vincent J.; Liu, Pengyuan; Bein, Kiflai; Brant, Kelly A.; Dopico, Richard A.; Di, Y. Peter; Jang, An-Soo; Dietsch, Maggie; Medvedovic, Mario; Li, Qian; Vuga, Louis J.; Kaminski, Naftali; You, Ming; Prows,
Fonte: American Thoracic Society Publicador: American Thoracic Society
Tipo: Artigo de Revista Científica
Publicado em 01/07/2010 Português
Relevância na Pesquisa
66.27%
Acute lung injury can be induced indirectly (e.g., sepsis) or directly (e.g., chlorine inhalation). Because treatment is still limited to supportive measures, mortality remains high (∼74,500 deaths/yr). In the past, accidental (railroad derailments) and intentional (Iraq terrorism) chlorine exposures have led to deaths and hospitalizations from acute lung injury. To better understand the molecular events controlling chlorine-induced acute lung injury, we have developed a functional genomics approach using inbred mice strains. Various mouse strains were exposed to chlorine (45 ppm × 24 h) and survival was monitored. The most divergent strains varied by more than threefold in mean survival time, supporting the likelihood of an underlying genetic basis of susceptibility. These divergent strains are excellent models for additional genetic analysis to identify critical candidate genes controlling chlorine-induced acute lung injury. Gene-targeted mice then could be used to test the functional significance of susceptibility candidate genes, which could be valuable in revealing novel insights into the biology of acute lung injury.

Atelectasis Induced by Thoracotomy Causes Lung Injury during Mechanical Ventilation in Endotoxemic Rats

Choi, Won-Il; Kwon, Kun Young; Kim, Jin Mo; Quinn, Deborah A.; Hales, Charles Albert; Seo, Jeong Wook
Fonte: The Korean Academy of Medical Sciences Publicador: The Korean Academy of Medical Sciences
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
66.26%
Atelectasis can impair arterial oxygenation and decrease lung compliance. However, the effects of atelectasis on endotoxemic lungs during ventilation have not been well studied. We hypothesized that ventilation at low volumes below functional residual capacity (FRC) would accentuate lung injury in lipopolysaccharide (LPS)-pretreated rats. LPS-pretreated rats were ventilated with room air at 85 breaths/min for 2 hr at a tidal volume of 10 mL/kg with or without thoracotomy. Positive end-expiratory pressure (PEEP) was applied to restore FRC in the thoracotomy group. While LPS or thoracotomy alone did not cause significant injury, the combination of endotoxemia and thoracotomy caused significant hypoxemia and hypercapnia. The injury was observed along with a marked accumulation of inflammatory cells in the interstitium of the lungs, predominantly comprising neutrophils and mononuclear cells. Immunohistochemistry showed increased inducible nitric oxide synthase (iNOS) expression in mononuclear cells accumulated in the interstitium in the injury group. Pretreatment with PEEP or an iNOS inhibitor (1400 W) attenuated hypoxemia, hypercapnia, and the accumulation of inflammatory cells in the lung. In conclusion, the data suggest that atelectasis induced by thoracotomy causes lung injury during mechanical ventilation in endotoxemic rats through iNOS expression.

Analysis of Regional Mechanics in Canine Lung Injury Using Forced Oscillations and 3D Image Registration

Cao, Kunlin; Christensen, Gary E.; Bates, Jason H. T.; Kaczka, David; Simon, Brett A
Fonte: Springer US Publicador: Springer US
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
66.27%
Acute lung injury is characterized by heterogeneity of regional mechanical properties, which is thought to be correlated with disease severity. The feasibility of using respiratory input impedance ((Z_{rs})) and computed tomographic (CT) image registration for assessing parenchymal mechanical heterogeneity was evaluated. In six dogs, measurements of ((Z_{rs})) before and after oleic acid injury at various distending pressures were obtained, followed by whole lung CT scans. Each ((Z_{rs})) spectrum was fit with a model incorporating variable distributions of regional compliances. CT image pairs at different inflation pressures were matched using an image registration algorithm, from which distributions of regional compliances from the resulting anatomic deformation fields were computed. Under baseline conditions, average model compliance decreased with increasing inflation pressure, reflecting parenchymal stiffening. After lung injury, these average compliances decreased at each pressure, indicating derecruitment, alveolar flooding, or alterations in intrinsic tissue elastance. However, average compliance did not change as inflation pressure increased, consistent with simultaneous recruitment and strain stiffening. Image registration revealed peaked distributions of regional compliances...

Incidence and mortality of acute lung injury and the acute respiratory distress syndrome in three Australian states

Bersten, A.; Edibam, C.; Hunt, T.; Moran, J.
Fonte: Amer Lung Assoc Publicador: Amer Lung Assoc
Tipo: Artigo de Revista Científica
Publicado em //2002 Português
Relevância na Pesquisa
76.1%
To determine the incidence and 28-d mortality rate for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) using the 1994 American–European Consensus Conference definitions, we prospectively screened every admission to all 21 adult intensive care units in the States of South Australia, Western Australia, and Tasmania (total population older than 15 yr of age estimated as 2,941,137), between October 1 and November 30, 1999. A total of 1,977 admissions were screened of which 168 developed ALI and 148 developed ARDS, which represents a first incidence of 34 and 28 cases per 100,000 per annum, respectively. The respective 28-d mortality rates were 32% and 34%. The most common predisposing factors for ALI were nonpulmonary sepsis (31%) and pneumonia (28%). Although the incidences of ALI and ARDS are higher and the mortality rates are lower than those reported from studies in other countries, multicenter international studies are required to exclude methodological differences as the cause for this finding.; Andrew D. Bersten, Cyrus Edibam, Tamara Hunt, John Moran and The Australian and New Zealand Intensive Care Society Clinical Trials Group

FMS-like tyrosine kinase 3 ligand treatment of mice aggravates acute lung injury in response to Streptococcus pneumoniae: Role of pneumolysin

Brumshagen, C.; Maus, R.; Bischof, A.; Ueberberg, B.; Bohling, J.; Osterholzer, J.; Ogunniyi, A.; Paton, J.; Welte, T.; Maus, U.
Fonte: Amer Soc Microbiology Publicador: Amer Soc Microbiology
Tipo: Artigo de Revista Científica
Publicado em //2012 Português
Relevância na Pesquisa
66.26%
FMS-like tyrosine kinase-3 ligand (Flt3L) is a dendritic cell (DC) growth and differentiation factor with potential in antitumor therapies and antibacterial immunization strategies. However, the effect of systemic Flt3L treatment on lung-protective immunity against bacterial infection is incompletely defined. Here, we examined the impact of deficient (in Flt3L knockout [KO] mice), normal (in wild-type [WT] mice), or increased Flt3L availability (in WT mice pretreated with Flt3L for 3, 5, or 7 days) on lung DC subset profiles and lung-protective immunity against the major lung-tropic pathogen, Streptococcus pneumoniae. Although in Flt3L-deficient mice the numbers of DCs positive for CD11b (CD11b(pos) DCs) and for CD103 (CD103(pos) DCs) were diminished, lung permeability, a marker of injury, was unaltered in response to S. pneumoniae. In contrast, WT mice pretreated with Flt3L particularly responded with increased numbers of CD11b(pos) DCs and with less pronounced numbers of CD103(pos) DCs and impaired bacterial clearance and with increased lung permeability following S. pneumoniae challenge. Notably, infection of Flt3L-pretreated mice with S. pneumoniae lacking the pore-forming toxin, pneumolysin (PLY), resulted in substantially less lung CD11b(pos) DCs activation and reduced lung permeability. Collectively...

Clinical review : The implications of experimental and clinical studies of recruitment maneuvers in acute lung injury

Piacentini Gómez, Enrique; Villagrá, Ana; López Aguilar, Josefina; Blanch Torra, Lluís
Fonte: Universidade Autônoma de Barcelona Publicador: Universidade Autônoma de Barcelona
Tipo: Artigo de Revista Científica Formato: application/pdf
Publicado em //2003 Português
Relevância na Pesquisa
66.27%
Mechanical ventilation can cause and perpetuate lung injury if alveolar overdistension, cyclic collapse, and reopening of alveolar units occur. The use of low tidal volume and limited airway pressure has improved survival in patients with acute lung injury or acute respiratory distress syndrome. The use of recruitment maneuvers has been proposed as an adjunct to mechanical ventilation to re-expand collapsed lung tissue. Many investigators have studied the benefits of recruitment maneuvers in healthy anesthetized patients and in patients ventilated with low positive end-expiratory pressure. However, it is unclear whether recruitment maneuvers are useful when patients with acute lung injury or acute respiratory distress syndrome are ventilated with high positive end-expiratory pressure, and in the presence of lung fibrosis or a stiff chest wall. Moreover, it is unclear whether the use of high airway pressures during recruitment maneuvers can cause bacterial translocation. This article reviews the intrinsic mechanisms of mechanical stress, the controversy regarding clinical use of recruitment maneuvers, and the interactions between lung infection and application of high intrathoracic pressures.