Partial liquid ventilation with perflubron attenuates in vivo oxidative damage to proteins and lipids

Rotta, Alexandre T.; Gunnarsson, Björn; Hernan, Lynn J.; Fuhrman, Bradley P.; Steinhorn, David M.

doi:10.1097/00003246-200001000-00033

Cited by 45 publications

(34 citation statements)

References 45 publications

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“…Our results are consistent with previous work suggesting important roles for inflammation, stress response, and the aberrant reactivation of developmental pathways in VILI. Various ontologies related to binding were associated with the response to ventilation, likely due to an elevated stress response as well as oxidative damage to DNA and proteins (51,67). However, our results for GO and Position-weight matrix (PWM) enrichment was done as for GO contained in the cross-species and baboon groups being bound by a particular TF (METHODS).…”

Section: Discussionmentioning

confidence: 99%

Highly conserved transcriptional responses to mechanical ventilation of the lung

Kompass¹,

Deslée

Moore

et al. 2010

Physiological Genomics

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Cross-species analysis of microarray data has shown improved discriminating power between healthy and diseased states. Computational approaches have proven effective in deciphering the complexity of human disease by identifying upstream regulatory elements and the transcription factors that interact with them. Here we used both methods to identify highly conserved transcriptional responses during mechanical ventilation, an important therapeutic treatment that has injurious side effects. We generated control and ventilated whole lung samples from the premature baboon model of bronchopulmonary dysplasia (BPD), processed them for microarray, and combined them with existing whole lung oligonucleotide microarray data from 85 additional control samples from mouse, rat, and human and 19 additional ventilated samples from mouse and rat. Of the 2,531 orthologs shared by all 114 samples, 60 were modulated by mechanical ventilation [false discovery rate (FDR)-adjusted q value ( qFDR) = 0.005, ANOVA]. These included transcripts encoding the transcription factors ATF3 and FOS. Because of compelling known roles for these transcription factors, we used computational methods to predict their targets in the premature baboon model of BPD, which included elastin (ELN), gastrin-releasing polypeptide (GRP), and connective tissue growth factor (CTGF). This approach identified highly conserved transcriptional responses to mechanical ventilation and may facilitate identification of therapeutic targets to reduce the side effects of this valuable treatment.

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Section: Discussionmentioning

confidence: 99%

Highly conserved transcriptional responses to mechanical ventilation of the lung

Kompass¹,

Deslée

Moore

et al. 2010

Physiological Genomics

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“…However, recent trials did not show any clinical benefit for patients treated with PLV when compared with CMV. Some studies have focused on antiinflammatory effects of PLV (2,7,9,(25)(26)(27). Because suppression of the inflammatory response might interfere with lung defense in case of bacterial pneumonia, possible interactions between bacteria and fluorocarbons need to be investigated systematically before recommendations can be given for clinical use of PLV.…”

Section: Discussionmentioning

confidence: 99%

Influence of Partial Liquid Ventilation on Bacterial Growth and Alveolar Expansion in Newborn Rabbits with Group B-Streptococcal Pneumonia

et al. 2003

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“…O processo de peroxidação lipídica causa a destruição de lipídeos presentes na membrana celular, resultando na formação de peróxidos lipídicos e aldeídos, como o 4-HNE 15,35 . Em um estudo anterior, demonstramos uma elevação de 4-HNE em animais lesados com endotoxina intravenosa tratados com ventilação convencional, enquanto que animais tratados com VLP apresentaram níveis de 4-HNE atenuados 16 . No presente estudo, animais tratados com VMC apresentaram níveis elevados de 4-HNE, em contraste com o grupo controle.…”

Section: Discussionunclassified

“…O dano oxidativo pulmonar foi quantificado através dos níveis de 4-hidroxinonenal (4-HNE), um marcador específi-co de peroxidação lipídica, através do método de Esterbauer & Cheeseman 15,16 .…”

Section: Análise Do Dano Oxidativounclassified

The impact of mechanical ventilation strategies that minimize atelectrauma in an experimental model of acute lung injury

Viana¹,

Sargentelli²,

Arruda³

et al. 2004

J Pediatr (Rio J)

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Objective: To evaluate whether ventilation strategies that target alveolar stabilization and prevention of atelectrauma would be associated with more favorable physiologic outcomes in a combined model of acute lung injury.Methods: Thirty-nine rabbits were instrumented and ventilated with FiO 2 of 1.0. Combined lung injury was induced by an infusion of lipopolysaccharide and tracheal saline lavage. Animals were randomized to receive conventional ventilation with tidal volume of 10 ml/kg, PEEP of 4 cm H 2 O; conventional ventilation with surfactant (Infasurf, 3 mg/kg IT); partial liquid ventilation (18 ml/kg of perflubron IT); or high-frequency oscillatory ventilation with mean airway pressure of 14 cm H 2 O and frequency of 4 Hz. Uninjured ventilated animals served as controls. Conventional ventilation with surfactant, partial liquid ventilation and control groups were ventilated with settings identical to the conventional ventilation group. Animals were studied for 4 hours, during which serial blood gas measurements were obtained. After sacrifice, lungs were harvested for injury grading by a microscopic lung injury score and measurement of 4-hydroxy-nonenal, a marker of lipid peroxidation.Results: Conventional ventilation resulted in hypoxia and greater evidence of lung injury. Animals treated with partial liquid ventilation, high-frequency oscillatory ventilation or conventional ventilation with surfactant had adequate oxygenation, but conventional ventilation with surfactant resulted in higher lung injury scores and increased pulmonary oxidative damage. Conclusion:Strategies that minimize atelectrauma (partial liquid ventilation and high-frequency oscillatory ventilation) are associated with adequate oxygenation and attenuated lung injury. Surfactant improves oxygenation in comparison to conventional ventilation alone but resulted in increased injury, presumably because the inadequately low PEEP was insufficient to stabilize the alveoli during expiration. ResumoObjetivo: Avaliar se estratégias ventilatórias que buscam a estabilização alveolar e a prevenção do atelectrauma estão associadas a desfechos fisiológicos mais favoráveis em um modelo experimental de lesão pulmonar aguda combinada.Métodos: Trinta e nove coelhos foram instrumentados e ventilados com uma fração inspirada de oxigênio (FiO 2 ) de 1,0. A lesão pulmonar foi induzida pela infusão venosa de lipopolissacarídeo de E. coli e por repetidas lavagens traqueais com solução salina. Os animais foram randomizados a receber ventilação mecânica convencional com volume corrente de 10 ml/kg, pressão expiratória final (PEEP) de 4 cm H 2 O; ventilação mecânica convencional com surfactante (Infasurf, 3 mg/kg, ET); ventilação líquida parcial (18 ml/kg de perflubron, ET); ou ventilação oscilatória de alta freqüência, com pressão média de via aérea de 14 cm H 2 O e freqüência de 10 Hz. Animais sadios submetidos a instrumentação e ventilação convencional serviram como controles. Os grupos ventilação mecânica convencional com surfactante, ventilação líquida...

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Partial liquid ventilation with perflubron attenuates in vivo oxidative damage to proteins and lipids

Abstract: Partial liquid ventilation attenuates oxidative damage to lipids and proteins during experimental acute lung injury. This finding is not caused by binding of lipid peroxidation products to perflubron or by the peroxyl radical scavenging properties of perflubron.

Cited by 45 publications

References 45 publications

Highly conserved transcriptional responses to mechanical ventilation of the lung

Highly conserved transcriptional responses to mechanical ventilation of the lung

Influence of Partial Liquid Ventilation on Bacterial Growth and Alveolar Expansion in Newborn Rabbits with Group B-Streptococcal Pneumonia

The impact of mechanical ventilation strategies that minimize atelectrauma in an experimental model of acute lung injury

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