Relation between respiratory mechanics, inflammation, and survival in experimental mechanical ventilation

Margit V. Szabari, Kazue Takahashi, Yan Feng, Joseph J. Locascio, Wei Chao, Edward A. Carter, Marcos F. Vidal Melo, Guido Musch

Research output: Contribution to journalArticle

3 Scopus citations


Low–tidal volume (VT) ventilation might protect healthy lungs from volutrauma but lead to inflammation resulting from other mechanisms, namely alveolar derecruitment and the ensuing alveolar collapse and tidal reexpansion. We hypothesized that the different mechanisms of low- and high-volume injury would be reflected in different mechanical properties being associated with development of pulmonary inflammation and mortality: an increase of hysteresis, reflecting progressive alveolar derecruitment, at low VT; an increase of elastance, as a result of overdistension, at higher VT. Mice were allocated to “protective” (6 ml/kg) or “injurious” (15–20 ml/kg) VT groups and ventilated for 16 hours or until death. We measured elastance and hysteresis; pulmonary IL-6, IL-1b, and MIP-2 (macrophage inflammatory protein 2); wet-to-dry ratio; and blood gases. Survival was greater in the protective group (60%) than in the injurious group (25%). Nonsurvivors showed increased pulmonary cytokines, particularly in the injurious group, with the increase of elastance reflecting IL-6 concentration. Survivors instead showed only modest increases of cytokines, independent of VT and unrelated to the increase of elastance. No single lung strain threshold could discriminate survivors from nonsurvivors. Hysteresis increased faster in the protective group, but, contrary to our hypothesis, its change was inversely related to the concentration of cytokines. In this model, significant mortality associated with pulmonary inflammation occurred even for strain values as low as about 0.8. Low VT improved survival. The accompanying increase of hysteresis was not associated with greater inflammation.

Original languageEnglish
Pages (from-to)179-188
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Issue number2
StatePublished - Feb 2019


  • Acute lung injury
  • Artificial respiration
  • Respiratory mechanics
  • Ventilator-induced lung injury

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