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Conflicting physiological and genomic cardiopulmonary effects of recruitment maneuvers in murine acute lung injury.

ABSTRACT: Low tidal volume ventilation, although promoting atelectasis, is a protective strategy against ventilator-induced lung injury. Deep inflation (DI) recruitment maneuvers restore lung volumes, but potentially compromise lung parenchymal and vascular function via repetitive overdistention. Our objective was to examine cardiopulmonary physiological and transcriptional consequences of recruitment maneuvers. C57/BL6 mice challenged with either PBS or LPS via aspiration were placed on mechanical ventilation (5 h) using low tidal volume inflation (TI; 8 ?l/g) alone or in combination with intermittent DIs (0.75 ml twice/min). Lung mechanics during TI ventilation significantly deteriorated, as assessed by forced oscillation technique and pressure-volume curves. DI mitigated the TI-induced alterations in lung mechanics, but induced a significant rise in right ventricle systolic pressures and pulmonary vascular resistances, especially in LPS-challenged animals. In addition, DI exacerbated the LPS-induced genome-wide lung inflammatory transcriptome, with prominent dysregulation of a gene cluster involving vascular processes, as well as increases in cytokine concentrations in bronchoalveolar lavage fluid and plasma. Gene ontology analyses of right ventricular tissue expression profiles also identified inflammatory signatures, as well as apoptosis and membrane organization ontologies, as potential elements in the response to acute pressure overload. Our results, although confirming the improvement in lung mechanics offered by DI, highlight a detrimental impact in sustaining inflammatory response and exacerbating lung vascular dysfunction, events contributing to increases in right ventricle afterload. These novel insights should be integrated into the clinical assessment of the risk/benefit of recruitment maneuver strategies.

SUBMITTER: Mekontso Dessap A

PROVIDER: S-EPMC3359949 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Conflicting physiological and genomic cardiopulmonary effects of recruitment maneuvers in murine acute lung injury.

Mekontso Dessap Armand A Voiriot Guillaume G Zhou Tong T Marcos Elisabeth E Dudek Steven M SM Jacobson Jeff R JR Machado Roberto R Adnot Serge S Brochard Laurent L Maitre Bernard B Garcia Joe G N JG

American journal of respiratory cell and molecular biology 20111201 4

Low tidal volume ventilation, although promoting atelectasis, is a protective strategy against ventilator-induced lung injury. Deep inflation (DI) recruitment maneuvers restore lung volumes, but potentially compromise lung parenchymal and vascular function via repetitive overdistention. Our objective was to examine cardiopulmonary physiological and transcriptional consequences of recruitment maneuvers. C57/BL6 mice challenged with either PBS or LPS via aspiration were placed on mechanical ventil ...[more]

PMID: 22135358

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Project description:With advances in supportive therapy in the last two decades, mortality rates from ALI/ARDS have improved somewhat, but remain around 30 to 40% with significant morbidity in survivors. Several promising treatments are in various stages of evaluation, but many have failed to prove beneficial in large randomized clinical trials (RCT). The first definitive step forward in ALI therapeutics occurred recently as a result of a large RCT demonstrating a mortality decrease from 40 to 31% with the use of low-volume ventilation strategies. From this, it is clear that the opportunity for successful intervention in ALI exists. However, therapeutic advances remain frustrated by the lack of complete understanding of ALI pathophysiology. This stresses the importance of integrating basic and clinical research of the molecular pathogenesis of this disease. The conclusions of a recent National Heart, Lung, and Blood Institute (NHLBI) Working Group on ALI support this type of research as a priority for future investigations of ALI. One of the areas of research given priority by this ALI Working Group is the issue of ALI severity progression and the role of cells of innate immunity in this process. Currently, the processes that determine which ALI patients progress to ARDS and which do not are unclear. As with many phenotype differences, there is most likely a genetic component involved. The basis for this has been demonstrated. For example, a surfactant protein B (SP-B) polymorphism appears to increase a patient’s risk of developing ALI from pneumonia. Additionally, a polymorphism in the promoter region of the gene for interleukin-6 (IL-6) has been associated with a poor prognosis in patients with ARDS. Understanding the intracellular processes of these genes and the cells expressing them in ALI progression could lead to the identification of molecular markers of ALI severity and eventually to the development of targeted therapies. An examination of genetically uniform animals will provide a clearer insight into the interaction between immune cells in ALI progression as well as guide future human experiments. Keywords: Time Series Design, ALI - acute lung injury, ARDS - acute respiratory distress syndrome, CLP - cecal ligation and puncture

Project description:ObjectivesThe aim of this study was to compare the effects of a sustained inflation alveolar recruiting maneuver (ARM) followed by 5 cmH2O of PEEP and a stepwise ARM, in dogs undergoing laparoscopic surgery.Materials and methodsTwenty adult dogs were enrolled in this prospective randomized clinical study. Dogs were premedicated with methadone intramuscularly (IM); anesthesia was induced with propofol intravenously (IV) and maintained with inhaled isoflurane in pure oxygen. The baseline ventilatory setting (BVS) was as follows: tidal volume of 15 mL/kg, inspiratory pause of 25%, inspiratory to expiratory ratio of 1:2, and the respiratory rate to maintain the end-tidal carbon dioxide between 45 and 55 mmHg. 10 min after pneumoperitoneum, randomly, 10 dogs underwent sustained inflation ARM followed by 5 cmH2O of PEEP (ARMi), while 10 dogs underwent a stepwise recruitment maneuver followed by the setting of the "best PEEP" (ARMc). Gas exchange, respiratory system mechanics, and hemodynamic were evaluated before the pneumoperitoneum induction (BASE), 10 min after the pneumoperitoneum (PP), 10 min after the recruitment (ARM), and 10 min after the pneumoperitoneum resolution (PostPP). Statistical analysis was performed with the ANOVA test (p < 0.05).ResultsStatic compliance decreased in both groups at PP (ARMc = 1.35 ± 0.21; ARMi = 1.16 ± 0.26 mL/cmH2O/kg) compared to BASE (ARMc = 1.78 ± 0.60; ARMi = 1.66 ± 0.66 mL/cmH2O/kg) and at ARM (ARMc = 1.71 ± 0.41; ARMi = 1.44 ± 0.84 mL/cmH2O/kg) and PostPP (ARMc = 1.75 ± 0.45; ARMi = 1.89 ± 0.59 mL/cmH2O/kg), and it was higher compared to PP and similar to BASE. The PaO2/FiO2, in both groups, was higher at ARM (ARMc = 455.11 ± 85.90; ARMi = 505.40 ± 31.70) and PostPP (ARMc = 521.30 ± 66.20; ARMi = 450.90 ± 70.60) compared to PP (ARMc = 369.53 ± 49.31; ARMi = 394.32 ± 37.72).Conclusion and clinical relevanceThe two ARMs improve lung function in dogs undergoing laparoscopic surgery similarly. Application of PEEP at the end of the ARMs prolonged the effects of the open-lung strategy.

Project description:BackgroundPositive-pressure mechanical ventilation is an essential therapeutic intervention, yet it causes the clinical syndrome known as ventilator-induced lung injury. Various lung protective mechanical ventilation strategies have attempted to reduce or prevent ventilator-induced lung injury but few modalities have proven effective. A model that isolates the contribution of mechanical ventilation on the development of acute lung injury is needed to better understand biologic mechanisms that lead to ventilator-induced lung injury.ObjectivesTo evaluate the effects of positive end-expiratory pressure and recruitment maneuvers in reducing lung injury in a ventilator-induced lung injury murine model in short- and longer-term ventilation.Methods5-12 week-old female BALB/c mice (n = 85) were anesthetized, placed on mechanical ventilation for either 2 hrs or 4 hrs with either low tidal volume (8 ml/kg) or high tidal volume (15 ml/kg) with or without positive end-expiratory pressure and recruitment maneuvers.ResultsAlteration of the alveolar-capillary barrier was noted at 2 hrs of high tidal volume ventilation. Standardized histology scores, influx of bronchoalveolar lavage albumin, proinflammatory cytokines, and absolute neutrophils were significantly higher in the high-tidal volume ventilation group at 4 hours of ventilation. Application of positive end-expiratory pressure resulted in significantly decreased standardized histology scores and bronchoalveolar absolute neutrophil counts at low- and high-tidal volume ventilation, respectively. Recruitment maneuvers were essential to maintain pulmonary compliance at both 2 and 4 hrs of ventilation.ConclusionsSigns of ventilator-induced lung injury are evident soon after high tidal volume ventilation (as early as 2 hours) and lung injury worsens with longer-term ventilation (4 hrs). Application of positive end-expiratory pressure and recruitment maneuvers are protective against worsening VILI across all time points. Dynamic compliance can be used guide the frequency of recruitment maneuvers to help ameloriate ventilator-induced lung injury.

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Conflicting physiological and genomic cardiopulmonary effects of recruitment maneuvers in murine acute lung injury.

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Conflicting physiological and genomic cardiopulmonary effects of recruitment maneuvers in murine acute lung injury.

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