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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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Histopathology of pulmonary tissue. Frozen lung sections were stained with H&E to analyze lung architecture and presence of granulocytes in pulmonary tissue. (a) Non-ventilated controls, (b) mice exposed to hyperoxia for four hours, and mice mechanically ventilated for (c) one, (d) two and (e) four hours. Magnification ×500.
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Figure 1: Histopathology of pulmonary tissue. Frozen lung sections were stained with H&E to analyze lung architecture and presence of granulocytes in pulmonary tissue. (a) Non-ventilated controls, (b) mice exposed to hyperoxia for four hours, and mice mechanically ventilated for (c) one, (d) two and (e) four hours. Magnification ×500.

Mentions: MV was applied to healthy mice to induce alveolar stretch. All mice survived the ventilatory protocol and produced urine throughout the experiment. Arterial blood gas analysis of ventilated mice showed a stable oxygen tension (PaO2) with carbon dioxide tension (PaCO2), pH and base excess (BE) within the physiological range (Table 2). In addition, pulmonary architecture was preserved during the experiment (Figure 1).


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)

Histopathology of pulmonary tissue. Frozen lung sections were stained with H&E to analyze lung architecture and presence of granulocytes in pulmonary tissue. (a) Non-ventilated controls, (b) mice exposed to hyperoxia for four hours, and mice mechanically ventilated for (c) one, (d) two and (e) four hours. Magnification ×500.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Histopathology of pulmonary tissue. Frozen lung sections were stained with H&E to analyze lung architecture and presence of granulocytes in pulmonary tissue. (a) Non-ventilated controls, (b) mice exposed to hyperoxia for four hours, and mice mechanically ventilated for (c) one, (d) two and (e) four hours. Magnification ×500.
Mentions: MV was applied to healthy mice to induce alveolar stretch. All mice survived the ventilatory protocol and produced urine throughout the experiment. Arterial blood gas analysis of ventilated mice showed a stable oxygen tension (PaO2) with carbon dioxide tension (PaCO2), pH and base excess (BE) within the physiological range (Table 2). In addition, pulmonary architecture was preserved during the experiment (Figure 1).

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