Ventilator-Induced Lung Injury Is Associated with Neutrophil Infiltration, Macrophage Activation, and TGF-β1 mRNA Upregulation in Rat Lungs

Imanaka, Hideaki; Shimaoka, Motomu; Matsuura, Nariaki; Nishimura, Masaji; Ohta, Nobuaki; Kiyono, Hiroshi

doi:10.1213/00000539-200102000-00029

Cited by 131 publications

(95 citation statements)

References 40 publications

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“…38 Hence, mechanical forces applied during artificial ventilation might be converted into early proinflammatory signals resulting in activation and adhesion of macrophages to the alveolar epithelium. 39,40 Decreased macrophage number recovered from lavage fluid after injurious ventilation has been reported previously. [39][40][41][42] We did not find significant differences in the number of recovered BALF cells and cytokine response between low and high V T groups, but low V T ventilation clearly resulted in impaired lung function.…”

Section: Discussionsupporting

confidence: 61%

“…39,40 Decreased macrophage number recovered from lavage fluid after injurious ventilation has been reported previously. [39][40][41][42] We did not find significant differences in the number of recovered BALF cells and cytokine response between low and high V T groups, but low V T ventilation clearly resulted in impaired lung function. Based on these findings, it seems reasonable to suggest that low V T ventilation of infant rats also causes significant mechanical stress presumably via atelectasis-related shear stress.…”

Section: Discussionsupporting

confidence: 61%

“…Third, apoptosis and necrosis during the process of lung injury are also possible causes for the decreased macrophage number derived from BALF in hemorrhage exposed and ventilated animals. [39][40][41] Since we did not directly assess migration, adhesion, or apoptosis of alveolar macrophages, based on our findings, we can only speculate that mechanical ventilation induced macrophage activation and increased IL-6 production with subsequent neutrophil recruitment.…”

Section: Discussionmentioning

confidence: 89%

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High Tidal Volume Ventilation Is Not Deleterious in Infant Rats Exposed to Severe Hemorrhage

Cannizzaro

Berry

Nicholls

et al. 2010

Journal of Trauma: Injury, Infection &Amp; Critical Care

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and key wordsBackground: Both high tidal volume (V T ) ventilation and hemorrhage induce acute lung injury in adult rodents. It is not known whether injurious ventilation augments lung injury in infant rats exposed to severe hemorrhage. Methods:Two week old rats were allocated to ventilation with V T 7 mL/kg and PEEP 5 cmH 2 O (low V T ) or V T 21 mL/kg and PEEP 1 (high V T ) for 4 h. Additional rats were subjected to volume-controlled hemorrhage and delayed saline resuscitation, followed by low V T or high V T ventilation for 4 h. Non-ventilated control groups were also included.Airway resistance and the coefficient of tissue elastance (H) were derived from respiratory input impedance measurements using the low-frequency forced oscillation technique. Pressure-volume curves were obtained at baseline and at the end of the study.Interleukin-6 (IL-6), macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor alpha (TNF-α) were determined in bronchoalveolar lavage fluid (BALF) and serum. Results:In both healthy and hemorrhage-exposed animals high V T resulted in reduced H (better lung compliance), and increased transcutaneous oxygen saturation. IL-6 in BALF was greater in ventilated animals when compared to non-ventilated controls, but not different between ventilated groups. No significant differences were found for all other inflammatory mediators, total protein concentration in BALF, and histology. Conclusion:High V T ventilation with low PEEP improves respiratory system mechanics without causing additional damage to healthy and hemorrhage-exposed infant rats after 4 3 h of ventilation. This study highlights the tolerance to high V T ventilation in infant rats and underscores the need for age-specific animal models.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 89%

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High Tidal Volume Ventilation Is Not Deleterious in Infant Rats Exposed to Severe Hemorrhage

Cannizzaro

Berry

Nicholls

et al. 2010

Journal of Trauma: Injury, Infection &Amp; Critical Care

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“…Wild-type C57BL/6 mice were intratracheally neutrophil infiltration, and increased thickness of the alveolar wall, as described in a previous study 12 .…”

Section: Methodssupporting

confidence: 60%

Neutrophil elastase ameliorates matrix metalloproteinase-9 to promote lipopolysaccharide-induced acute lung injury in mice 1

Guo

Zhang

et al. 2016

Acta Cir. Bras.

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PURPOSE:To investigate the regulatory roles of neutrophil elastase (NE) and matrix metalloproteinase-9 (MMP-9) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. METHODS:To construct LPS-induced ALI mouse models, wild-type C57BL/6 mice were administered 5.0 mg/kg of LPS through endotracheal, and/or 1.0 mg/kg of ONO-5046, and/or 20.0 mg/kg of chemically modified tetracycline-3 (CMT-3) by gavage. The levels of MMP-9, tissue inhibitor of metalloprotease-1, interleukin (IL)-6 were detected by real time RT-PCR at 6 h, 24 h and 48 h, and tumor necrosis factor (TNF), lung wet-dry weight ratio, white blood cell (WBC) count and polymorphonuclear (PMN) count in bronchoalveolar lavage fluid (BALF) were tested at 48 h after administration. The 5-day survival analysis of the ALI mice was also performed. RESULTS:Both ONO-5046 and CMT-3, regardless of being used individually or combined, significantly reduced the levels of MMP-9, IL-6, and TNF in lung tissue as well as in BALF, and the WBC and PMN count in BALF. Combined treatment with ONO-5046 and CMT-3 remarkably improved the survival rate of ALI mice. CONCLUSION:Neutrophil elastase synergizes with matrix metalloproteinase-9 to promote and regulate the release of inflammatory mediators and the infiltration of inflammatory cells, consequently affecting the survival of lipopolysaccharide-induced acute lung injury mice.

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“…We used a relatively injurious VILI model in rats, which resulted in lung injury that features inflammation, and edema as assessed by cell count, TNF-␣ production, and protein in the BALF (25,26). We performed TUNEL assay in our lung tissues and did not observe evidence of cell death after VILI (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Inhaled Carbon Monoxide Confers Antiinflammatory Effects against Ventilator-induced Lung Injury

Dolinay

Szilasi

Liu

et al. 2004

Am J Respir Crit Care Med

138

127

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Ventilator-induced lung injury (VILI) is a major cause of morbidity and mortality in intensive care units. The stress-inducible gene product, heme oxygenase-1, and carbon monoxide (CO), a major byproduct of heme oxygenase catalysis of heme, have been shown to confer potent antiinflammatory effects in models of tissue and cellular injury. In this study, we observed increased expression of heme oxygenase-1 mRNA and protein in a rat model of VILI. To assess the physiologic function of heme oxygenase-1 induction in VILI, we determined whether low concentration of inhaled CO could serve to protect the lung against VILI. Low concentration of inhaled CO significantly reduced tumor necrosis factor-␣ levels and total cell count in lavage fluid, while simultaneously elevating levels of antiinflammatory interleukin-10 levels. To better characterize the mechanism of CO-mediated antiinflammatory effects, we examined key signaling pathways, which may mediate CO-induced antiinflammatory effects. We demonstrate that inhaled CO exerts antiinflammatory effects in VILI via the p38 mitogen-activated protein kinase pathway but independent of activator protein-1 and nuclear factor-B pathways. Our data lead to a tempting speculation that inhaled CO might be useful in minimizing VILI. Keywords: cytokines; heme oxygenase-1; p38 MAPKAccording to an international study, an average of 39% of intensive care unit patients requires mechanical ventilation worldwide (1). Many of these patients develop ventilator-induced lung injury (VILI) (2). Eventually VILI contributes to acute respiratory distress syndrome (ARDS), which has a 40 to 50% mortality rate (3). Although clinical trials showed that ARDS/VILI-related mortality could be attenuated with lower tidal volume ventilation, positive end-expiratory pressure (PEEP) ventilation, and more recently, with recruitment maneuver combined with protective ventilation strategy, the syndrome remains a major problem in intensive care units (3)(4)(5).It is established that mechanical ventilators that apply high volumes and pressures can lead to increased alveolar-capillary permeability (6). This loss of compartmentalization results in increased fluid influx to the alveoli from the capillaries, causing pulmonary edema. The injured or ruptured cells attract neutrophil leukocytes and activate alveolar macrophages, causing inflammation in the lung (6). Tremblay and colleagues have suggested that ventilation can provoke an inflammatory response in the distal airway and alveolar cells (7), manifested by increased production of proinflammatory cytokines. It is speculated that the released proinflammatory cytokines could enter the circulation causing inflammation in other systemic organs. In addition, the previously diseased or injured lungs are more susceptible to subsequent mechanical ventilation, releasing more proinflammatory cytokines than healthy lungs, perhaps reflecting the cumulative effects of multiple injuries (8, 9). Lipopolysaccharide (LPS), acid aspiration, and cecal ligation/perforation-induced sep...

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Ventilator-Induced Lung Injury Is Associated with Neutrophil Infiltration, Macrophage Activation, and TGF-β1 mRNA Upregulation in Rat Lungs

Cited by 131 publications

References 40 publications

High Tidal Volume Ventilation Is Not Deleterious in Infant Rats Exposed to Severe Hemorrhage

High Tidal Volume Ventilation Is Not Deleterious in Infant Rats Exposed to Severe Hemorrhage

Neutrophil elastase ameliorates matrix metalloproteinase-9 to promote lipopolysaccharide-induced acute lung injury in mice 1

Inhaled Carbon Monoxide Confers Antiinflammatory Effects against Ventilator-induced Lung Injury

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