Hypercapnic acidosis attenuates ventilation-induced lung injury by a nuclear factor-κB–dependent mechanism

Contreras, Maya; Ansari, Bilal; Curley, Gerard F.; Higgins, Brendan D.; Hassett, Patrick; O’Toole, Daniel; Laffey, John G.

doi:10.1097/ccm.0b013e318258f8b4

Cited by 77 publications

(84 citation statements)

References 36 publications

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“…Stretch injury due to mechanical ventilation could have been avoided by hypercapnic acidosis, and no growth may have been noticed in blood cultures, a suspicion that has been supported in the literature. [17,18] A third difference between previous studies and the present is that, despite fluid resuscitation, MAP decreased, compared to baseline, in all groups except for the control group by the end of the study. It is thought that hypotension due to impaired circulation and repetitive opening and closing may have made the modified sigh group more susceptible to lung injury.…”

Section: Ergin öZcan Et Al Effects Of Different Recruitment Maneuvercontrasting

confidence: 52%

The effects of different recruitment maneuvers on bacterial translocation and ventilatory induced lung injury

Ozcan

Akıncı

Edipoğlu

et al. 2015

Ulus Travma Acil Cerrahi Derg

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Section: Ergin öZcan Et Al Effects Of Different Recruitment Maneuvercontrasting

confidence: 52%

The effects of different recruitment maneuvers on bacterial translocation and ventilatory induced lung injury

Ozcan

Akıncı

Edipoğlu

et al. 2015

Ulus Travma Acil Cerrahi Derg

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“…Furthermore, mechanical stretching has been demonstrated to induce activation of NF-κB in lung fibroblasts and A549 cells (18,24). Activation of the NF-κB signaling pathway may be a key mechanism by which excessive stretch results in cellular activation, inflammation, and injury (25). In the present study, the expression of p-NF-κB in cells preconditioned at physiologically relevant amplitude CS (5% elongation) for 30, 60 and 120 min was determined and revealed obvious reductions.…”

Section: Discussionmentioning

confidence: 94%

Preconditioning of physiological cyclic stretch inhibits the inflammatory response induced by pathologically mechanical stretch in alveolar epithelial cells

Fang

et al. 2017

Exp Ther Med

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Abstract. The aim of the present study was to investigate the effects of preconditioning of physiological cyclic stretch (CS) on the overexpression of early pro-inflammatory cytokines [including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-8] during the inflammatory response induced by pathologically mechanical stretch in lung epithelial cells, and to determine its molecular mechanism of action. Cells were subjected to 5% CS for various durations (0,15, 30, 60 and 120 min) prior to 6 h treatment with pathological 20% CS. In a separate experiment, cells were preconditioned with physiological 5% CS or incubated with a nuclear factor (NF)-κB inhibitor, pyrroldine dithiocarbamate (PDTC). The expression levels of inflammatory mediators were measured using reverse transcription-quantitative polymerase chain reaction. NF-κB was quantified using western blot analysis. Preconditioning with physiological 5% CS for 30, 60 and 120 min was demonstrated to significantly attenuate the release of pathologically mechanical stretch-induced early pro-inflammatory cytokines (TNF-α, IL-1β and IL-8) in alveolar epithelial cells (P<0.05) and significantly reduce the expression of NF-κB (P<0.05). Peak suppression was observed in cells preconditioned for 60 min. In the second set of experiments, it was demonstrated that mechanical stretch-induced release of TNF-α, IL-1β and IL-8 was significantly inhibited by both PDTC pretreatment and 5% CS pretreatment alone (all P<0.05). Furthermore, significant inhibition was also observed when both 5% CS pretreatment and PDTC pretreatment was used on mechanical stretch-induced cells (P<0.05), which was markedly greater than the inhibition induced by either pretreatment alone. The present findings suggest that preconditioning with physiological 5% CS is able to inhibit the inflammatory response induced by pathologically mechanical stretch in alveolar epithelial cells. These anti-inflammatory effects are induced, at least in part, by suppressing the NF-κB signaling pathway.

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“…In ALI and ARDS, permissive hypercapnia 45,46 is preferred over strict normoventilation, and hypercapnic acidosis may also affect inflammation and oxygenation. 47,48 Avoidance of 1.0 Fio 2 , as performed in previous studies, 12 may also have influenced the results because of the time-dependent impact of oxygen on pulmonary damage and mortality. 49,50 We used a maximum Fio 2 of 0.7, however, which is consistent with clinical care.…”

Section: Discussionmentioning

confidence: 95%

Sevoflurane Abolishes Oxygenation Impairment in a Long-Term Rat Model of Acute Lung Injury

Kellner

Müller

Piegeler

et al. 2017

Anesthesia &Amp; Analgesia

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BACKGROUND Patients experiencing acute lung injury (ALI) often need mechanical ventilation for which sedation may be required. In such patients, usually the first choice an intravenously administered drug. However, growing evidence suggests that volatile anesthetics such as sevoflurane are a valuable alternative. In this study, we evaluate pulmonary and systemic effects of long-term (24-hour) sedation with sevoflurane compared with propofol in an in vivo animal model of ALI. METHODS Adult male Wistar rats were subjected to ALI by intratracheal lipopolysaccharide (LPS) application, mechanically ventilated and sedated for varying intervals up to 24 hours with either sevoflurane or propofol. Vital parameters were monitored, and arterial blood gases were analyzed. Inflammation was assessed by the analysis of bronchoalveolar lavage fluid (BALF), cytokines (monocyte chemoattractant protein-1 [MCP-1], cytokine-induced neutrophil chemoattractant protein-1 [CINC-1], interleukin , IL-12/12a, transforming growth factor-, and IL-10) in blood and lung tissue and inflammatory cells. The alveolocapillary barrier was indirectly assessed by wet-to-dry ratio, albumin, and total protein content in BALF. Results are presented as mean ± standard deviation. RESULTS After 9 hours of ventilation and sedation, oxygenation index was higher in the LPS/sevoflurane (LPS-S) than in the LPS/propofol group (LPS-P) and reached 400 ± 67 versus 262 ± 57 mm Hg after 24 hours (P < .001). Cell count in BALF in sevoflurane-treated animals was lower after 18 hours (P = .001) and 24 hours (P < .001) than in propofol controls. Peak values of CINC-1 and IL-6 in BALF were lower in LPS-S versus LPS-P animals (CINC-1: 2.7 ± 0.7 vs 4.0 ± 0.9 ng/mL; IL-6: 9.2 ± 2.3 vs 18.9 ± 7.1 pg/mL, both P < .001), whereas IL-10 and MCP-1 did not differ. Also messenger RNAs of CINC-1, IL-6, IL-12a, and IL-10 were significantly higher in LPS-P compared with LPS-S. MCP-1 and transforming growth factor-showed no differences. Wet-to-dry ratio was lower in LPS-S (5.4 ± 0.2 vs 5.7 ± 0.2, P = .016). Total protein in BALF did not differ between P-LPS and S-LPS groups. CONCLUSIONS Long-term sedation with sevoflurane compared with propofol improves oxygenation and attenuates the inflammatory response in LPS-induced ALI. Our findings suggest that sevoflurane may improve lung function when used for sedation in patients with ALI. Bacterial lipopolysaccharides (LPSs) are complex glycolipids found on the outer membrane of Gram-negative bacteria 10 and have been utilized to examine in vitro and in vivo inflammatory responses. [10][11][12] Other markers of ALI include endothelial barrier disruption, recruitment and transmigration of neutrophils, and development of a protein-and neutrophil-rich (noncardiogenic) pulmonary edema. [13][14][15][16] According to current guidelines, intravenous propofol, midazolam, and dexmedetomidine are recommended for sustained sedation in critically ill patients. 17,18 However, since the introduction of the Anaesthetic Conserving Device (AnaConDa; S...

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Hypercapnic acidosis attenuates ventilation-induced lung injury by a nuclear factor-κB–dependent mechanism

Abstract: Hypercapnic acidosis attenuated ventilation-induced lung injury independent of injury severity and decreased mechanical stretch-induced epithelial injury and death, via a nuclear factor-κB-dependent mechanism.

Cited by 77 publications

References 36 publications

The effects of different recruitment maneuvers on bacterial translocation and ventilatory induced lung injury

The effects of different recruitment maneuvers on bacterial translocation and ventilatory induced lung injury

Preconditioning of physiological cyclic stretch inhibits the inflammatory response induced by pathologically mechanical stretch in alveolar epithelial cells

Sevoflurane Abolishes Oxygenation Impairment in a Long-Term Rat Model of Acute Lung Injury

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