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Published on: April 7, 2021
Low-tidal-volume prevent ventilation induced inflammation in a mouse model of sepsis
Olaf Boehm1, Marc Rohner1, Heidi Ehrentraut1
1Department of Anesthesiology and Intensive Care Medicine, Rheinische Friedrich-Wilhelms-University Medical Center, Bonn, Germany.
Background And Goal Of The Study:
Pulmonary inflammation, increased vascular permeability, and pulmonary edema, occur in response to primary pulmonary infections like pneumonia but are also evident in endotoxemia or sepsis. Mechanical ventilation augments pre-existing lung injury and inflammation resulting from exposure to microbial products. The objective of this study was to test the hypothesis that low-tidal-volume prevent ventilation induced lung injury in sepsis.
Materials And Methods:
10-12-week-old male C57BL/6N-mice received an intraperitoneal (i.p.) injection with equipotent dosages of LPS, 1668-thioate, 1612-thioate, or PBS. 120 min after injection, mice were randomized to low- (LV, 7 ± 1 ml/kg) or high-tidal-volume (HV, 25 ± 1 ml/kg) ventilation. Hemodynamic and ventilatory parameters were recorded and inflammatory markers were analyzed form BAL that was generated after 90 minute ventilation.
Results And Discussion:
Arterial blood pressures declined during mechanical ventilation in all groups. pO2 decreased in LPS injected and CO2 increased in sham, LPS, and 1612-thioate administered mice at 45 min and in 1668-thioate injected mice after 90 minute LV ventilation compared to respective HV groups. BAL protein concentrations increased in HV ventilated and 1668- or 1612-thioat pre-treated mice. BAL TNF-α protein concentrations increased in both LPS- and 1668-thioate-injected and IL-1β protein concentrations only in LPS-injected and HV ventilated mice. Most notably, no increased protein concentrations were observed in any of the LV ventilated groups.
Conclusion:
We conclude that low-tidal-volume ventilation may be a potential strategy for the prevention of ventilator induced lung injury in a murine model of systemic TLR agonist induced lung injury.
Insights
Low-tidal-volume ventilation may prevent ventilator-induced lung injury in sepsis models. This study found no increased protein concentrations in low-tidal-volume ventilated groups, suggesting a protective strategy against lung inflammation.
Area of Science:
- Pulmonary Medicine
- Critical Care Medicine
- Immunology
Background:
- Sepsis and pneumonia cause pulmonary inflammation, increased vascular permeability, and edema.
- Mechanical ventilation can worsen existing lung injury from microbial products.
Purpose of the Study:
- To investigate if low-tidal-volume ventilation prevents ventilator-induced lung injury (VILI) in a sepsis model.
Main Methods:
- Mice were injected with lipopolysaccharide (LPS) or Toll-like receptor (TLR) agonists.
- Mice were then ventilated with either low-tidal-volume (LV) or high-tidal-volume (HV) for 90 minutes.
- Hemodynamic parameters and inflammatory markers in bronchoalveolar lavage (BAL) fluid were analyzed.
Main Results:
- Arterial blood pressure decreased in all groups during ventilation.
- HV ventilation increased BAL protein, TNF-α, and IL-1β in LPS-injected mice.
- LV ventilation did not increase BAL protein concentrations in any group, even with LPS or TLR agonist pre-treatment.
Conclusions:
- Low-tidal-volume ventilation may prevent VILI in a murine model of TLR agonist-induced lung injury.
- This strategy shows promise for managing lung injury in sepsis patients requiring mechanical ventilation.
