A short duration of mechanical ventilation alters redox status in the diaphragm and aggravates inflammation in septic mice

Respir Physiol Neurobiol. 2025 Jan:331:104361. doi: 10.1016/j.resp.2024.104361. Epub 2024 Oct 19.

Abstract

Background: Mechanical ventilation (MV) is a life support method used to treat patients with respiratory failure. High tidal volumes during MV can cause ventilator-induced lung injury (VILI), but also affect other organs, such as the diaphragm (Dia) causing ventilator-induced diaphragmatic dysfunction (VIDD). VIDD is often associated with a complicated course on MV. Sepsis can induce inflammation and oxidative stress, contributing to the impairment of the Dia and worsening of the prognosis. This study evaluated the additive or synergistic effects of a short course of mechanical ventilation on Dia in healthy and septic adult mice.

Methods: 32 adult male C57BL/6 mice were randomly into four groups: Control (CG), non-ventilated animals instilled with saline solution (PBS1x); Lipopolysaccharide (LPS), non-ventilated animals instilled with PBS solution containing lipopolysaccharide; Mechanical Ventilation (MV) for 1 h, ventilated animals instilled with PBS solution; and Mechanical Ventilation and LPS (MV+LPS), ventilated animals instilled with PBS solution containing LPS. At the end of the experimental protocol, the animals were euthanized, then blood and diaphragm tissue samples were collected.

Results: Evaluation of leukocyte/blood parameters and diaphragm muscle showed that MV, LPS and the combination of both were able to increase neutrophil count, creatine kinase, inflammatory mediators and oxidative stress in all groups compared to the control. MV and sepsis combined had additive effects on inflammation and lipid peroxidation.

Conclusions: A short course of Mechanical ventilation promotes inflammation and oxidative stress and, its combination with sepsis further increases local and systemic inflammation.

Keywords: Diaphragm; Inflammation; Mechanical ventilation; Oxidative stress; Sepsis.

MeSH terms

  • Animals
  • Diaphragm* / metabolism
  • Diaphragm* / physiopathology
  • Disease Models, Animal
  • Inflammation* / metabolism
  • Lipopolysaccharides* / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Oxidation-Reduction
  • Oxidative Stress / physiology
  • Respiration, Artificial* / adverse effects
  • Sepsis* / metabolism
  • Time Factors

Substances

  • Lipopolysaccharides