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Ventilator-induced endothelial activation and inflammation in the lung and distal organs.

Hegeman MA, Hennus MP, Heijnen CJ, Specht PA, Lachmann B, Jansen NJ, van Vught AJ, Cobelens PM - Crit Care (2009)

Bottom Line: Alveolar stretch imposed by MV did not only induce de novo synthesis of adhesion molecules in the lung but also in organs distal to the lung, like liver and kidney.No activation was observed in the brain.In addition, we demonstrated elevated cytokine and chemokine expression in pulmonary, hepatic and renal tissue after MV which was accompanied by enhanced recruitment of granulocytes to these organs.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Psychoneuroimmunology, University Medical Center Utrecht, Utrecht, 3584 EA, The Netherlands. m.a.hegeman@umcutrecht.nl

ABSTRACT

Introduction: Results from clinical studies have provided evidence for the importance of leukocyte-endothelial interactions in the pathogenesis of pulmonary diseases such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), as well as in systemic events like sepsis and multiple organ failure (MOF). The present study was designed to investigate whether alveolar stretch due to mechanical ventilation (MV) may evoke endothelial activation and inflammation in healthy mice, not only in the lung but also in organs distal to the lung.

Methods: Healthy male C3H/HeN mice were anesthetized, tracheotomized and mechanically ventilated for either 1, 2 or 4 hours. To study the effects of alveolar stretch in vivo, we applied a MV strategy that causes overstretch of pulmonary tissue i.e. 20 cmH2O peak inspiratory pressure (PIP) and 0 cmH2O positive end expiratory pressure (PEEP). Non-ventilated, sham-operated animals served as a reference group (non-ventilated controls, NVC).

Results: Alveolar stretch imposed by MV did not only induce de novo synthesis of adhesion molecules in the lung but also in organs distal to the lung, like liver and kidney. No activation was observed in the brain. In addition, we demonstrated elevated cytokine and chemokine expression in pulmonary, hepatic and renal tissue after MV which was accompanied by enhanced recruitment of granulocytes to these organs.

Conclusions: Our data implicate that MV causes endothelial activation and inflammation in mice without pre-existing pulmonary injury, both in the lung and distal organs.

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Ventilator-induced endothelial activation and inflammation in pulmonary tissue. In total lung homogenates, mRNA expression of the adhesion molecules (a) E-selectin, (b) vascular cell adhesion molecule (VCAM)-1, (c) intercellular adhesion molecule (ICAM)-1 and (d) platelet-endothelial cell adhesion molecule (PECAM)-1 was determined by quantitative real time RT-PCR. In addition, we studied ventilator-induced pulmonary inflammation by measuring mRNA expression of the pro-inflammatory cytokines (e) IL-1β and (f) TNF-α and the chemokine (g) keratinocyte-derived chemokine (KC). In total lung homogenates, (h) myeloperoxidase (MPO) activity was determined as a measure of granulocyte infiltration. Data are expressed as mean ± standard error of the mean of four to eight mice for each group (* P < 0.05, ** P < 0.01, *** P < 0.001 vs. non-ventilated controls (NVC)). 1 h = mechanically ventilated for one hour; 2 h = mechanically ventilated for two hours; 4 h = mechanically ventilated for four hours; O2 = hyperoxia for four hours; GAPDH = glyceraldehyde 3-phosphate dehydrogenase.
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Figure 2: Ventilator-induced endothelial activation and inflammation in pulmonary tissue. In total lung homogenates, mRNA expression of the adhesion molecules (a) E-selectin, (b) vascular cell adhesion molecule (VCAM)-1, (c) intercellular adhesion molecule (ICAM)-1 and (d) platelet-endothelial cell adhesion molecule (PECAM)-1 was determined by quantitative real time RT-PCR. In addition, we studied ventilator-induced pulmonary inflammation by measuring mRNA expression of the pro-inflammatory cytokines (e) IL-1β and (f) TNF-α and the chemokine (g) keratinocyte-derived chemokine (KC). In total lung homogenates, (h) myeloperoxidase (MPO) activity was determined as a measure of granulocyte infiltration. Data are expressed as mean ± standard error of the mean of four to eight mice for each group (* P < 0.05, ** P < 0.01, *** P < 0.001 vs. non-ventilated controls (NVC)). 1 h = mechanically ventilated for one hour; 2 h = mechanically ventilated for two hours; 4 h = mechanically ventilated for four hours; O2 = hyperoxia for four hours; GAPDH = glyceraldehyde 3-phosphate dehydrogenase.

Mentions: We studied the effect of MV on endothelial activation in pulmonary tissue by measuring de novo synthesis of adhesion molecules. Compared with NVC, enhanced mRNA expression of E-selectin and VCAM-1 was noticed after two and four hours of MV (Figures 2a and 2b). No ventilator-induced changes in ICAM-1 and PECAM-1 mRNA were found in the lung (Figures 2c and 2d).


Ventilator-induced endothelial activation and inflammation in the lung and distal organs.

Hegeman MA, Hennus MP, Heijnen CJ, Specht PA, Lachmann B, Jansen NJ, van Vught AJ, Cobelens PM - Crit Care (2009)

Ventilator-induced endothelial activation and inflammation in pulmonary tissue. In total lung homogenates, mRNA expression of the adhesion molecules (a) E-selectin, (b) vascular cell adhesion molecule (VCAM)-1, (c) intercellular adhesion molecule (ICAM)-1 and (d) platelet-endothelial cell adhesion molecule (PECAM)-1 was determined by quantitative real time RT-PCR. In addition, we studied ventilator-induced pulmonary inflammation by measuring mRNA expression of the pro-inflammatory cytokines (e) IL-1β and (f) TNF-α and the chemokine (g) keratinocyte-derived chemokine (KC). In total lung homogenates, (h) myeloperoxidase (MPO) activity was determined as a measure of granulocyte infiltration. Data are expressed as mean ± standard error of the mean of four to eight mice for each group (* P < 0.05, ** P < 0.01, *** P < 0.001 vs. non-ventilated controls (NVC)). 1 h = mechanically ventilated for one hour; 2 h = mechanically ventilated for two hours; 4 h = mechanically ventilated for four hours; O2 = hyperoxia for four hours; GAPDH = glyceraldehyde 3-phosphate dehydrogenase.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC2811914&req=5

Figure 2: Ventilator-induced endothelial activation and inflammation in pulmonary tissue. In total lung homogenates, mRNA expression of the adhesion molecules (a) E-selectin, (b) vascular cell adhesion molecule (VCAM)-1, (c) intercellular adhesion molecule (ICAM)-1 and (d) platelet-endothelial cell adhesion molecule (PECAM)-1 was determined by quantitative real time RT-PCR. In addition, we studied ventilator-induced pulmonary inflammation by measuring mRNA expression of the pro-inflammatory cytokines (e) IL-1β and (f) TNF-α and the chemokine (g) keratinocyte-derived chemokine (KC). In total lung homogenates, (h) myeloperoxidase (MPO) activity was determined as a measure of granulocyte infiltration. Data are expressed as mean ± standard error of the mean of four to eight mice for each group (* P < 0.05, ** P < 0.01, *** P < 0.001 vs. non-ventilated controls (NVC)). 1 h = mechanically ventilated for one hour; 2 h = mechanically ventilated for two hours; 4 h = mechanically ventilated for four hours; O2 = hyperoxia for four hours; GAPDH = glyceraldehyde 3-phosphate dehydrogenase.
Mentions: We studied the effect of MV on endothelial activation in pulmonary tissue by measuring de novo synthesis of adhesion molecules. Compared with NVC, enhanced mRNA expression of E-selectin and VCAM-1 was noticed after two and four hours of MV (Figures 2a and 2b). No ventilator-induced changes in ICAM-1 and PECAM-1 mRNA were found in the lung (Figures 2c and 2d).

Bottom Line: Alveolar stretch imposed by MV did not only induce de novo synthesis of adhesion molecules in the lung but also in organs distal to the lung, like liver and kidney.No activation was observed in the brain.In addition, we demonstrated elevated cytokine and chemokine expression in pulmonary, hepatic and renal tissue after MV which was accompanied by enhanced recruitment of granulocytes to these organs.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Psychoneuroimmunology, University Medical Center Utrecht, Utrecht, 3584 EA, The Netherlands. m.a.hegeman@umcutrecht.nl

ABSTRACT

Introduction: Results from clinical studies have provided evidence for the importance of leukocyte-endothelial interactions in the pathogenesis of pulmonary diseases such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), as well as in systemic events like sepsis and multiple organ failure (MOF). The present study was designed to investigate whether alveolar stretch due to mechanical ventilation (MV) may evoke endothelial activation and inflammation in healthy mice, not only in the lung but also in organs distal to the lung.

Methods: Healthy male C3H/HeN mice were anesthetized, tracheotomized and mechanically ventilated for either 1, 2 or 4 hours. To study the effects of alveolar stretch in vivo, we applied a MV strategy that causes overstretch of pulmonary tissue i.e. 20 cmH2O peak inspiratory pressure (PIP) and 0 cmH2O positive end expiratory pressure (PEEP). Non-ventilated, sham-operated animals served as a reference group (non-ventilated controls, NVC).

Results: Alveolar stretch imposed by MV did not only induce de novo synthesis of adhesion molecules in the lung but also in organs distal to the lung, like liver and kidney. No activation was observed in the brain. In addition, we demonstrated elevated cytokine and chemokine expression in pulmonary, hepatic and renal tissue after MV which was accompanied by enhanced recruitment of granulocytes to these organs.

Conclusions: Our data implicate that MV causes endothelial activation and inflammation in mice without pre-existing pulmonary injury, both in the lung and distal organs.

Show MeSH
Related in: MedlinePlus