How High Tidal Volume Mechanical Ventilation Affects Lung Injury
Author Information
Author(s): Damarla Mahendra, Hasan Emile, Boueiz Adel, Le Anne, Pae Hyun Hae, Montouchet Calypso, Kolb Todd, Simms Tiffany, Myers Allen, Kayyali Usamah S., Gaestel Matthias, Peng Xinqi, Reddy Sekhar P., Damico Rachel, Hassoun Paul M.
Primary Institution: Johns Hopkins University School of Medicine
Hypothesis
We hypothesized that MK2 activation via p38 MAP kinase induced HSP25 phosphorylation, in response to mechanical stress, leads to actin stress fiber formation and endothelial barrier dysfunction.
Conclusion
High tidal volume mechanical ventilation increases lung permeability through the activation of the p38 MAP kinase-MK2-HSP25 signaling pathway.
Supporting Evidence
- High tidal volume mechanical ventilation resulted in significant phosphorylation of p38 MAP kinase, MK2, and HSP25.
- MK2−/− mice were resistant to increases in lung permeability in response to high tidal volume mechanical ventilation.
- Inhibition of p38 MAP kinase or MK2 prevented the increase in lung permeability.
- Actin polymerization was significantly higher in response to high tidal volume compared to low tidal volume or spontaneous breathing.
Takeaway
When doctors use high tidal volume ventilation, it can hurt the lungs by making them leak. This study found that blocking certain signals can help protect the lungs.
Methodology
Mice were exposed to mechanical ventilation with different tidal volumes, and lung tissues were analyzed for various markers of injury and permeability.
Limitations
The study lacks the ability to localize the site of vascular permeability and may not account for other signaling pathways involved.
Participant Demographics
Male C57BL/6J mice aged 10–12 weeks.
Statistical Information
P-Value
<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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