Modulation of stress versus time product during mechanical ventilation influences inflammation as well as alveolar epithelial and endothelial response in rats

Anesthesiology. 2015 Jan;122(1):106-16. doi: 10.1097/ALN.0000000000000415.

Abstract

Background: Mechanical ventilation can lead to lung biotrauma when mechanical stress exceeds safety thresholds. The authors investigated whether the duration of mechanical stress, that is, the impact of a stress versus time product (STP), influences biotrauma. The authors hypothesized that higher STP levels are associated with increased inflammation and with alveolar epithelial and endothelial cell injury.

Methods: In 46 rats, Escherichia coli lipopolysaccharide (acute lung inflammation) or saline (control) was administered intratracheally. Both groups were protectively ventilated with inspiratory-to-expiratory ratios 1:2, 1:1, or 2:1 (n = 12 each), corresponding to low, middle, and high STP levels (STPlow, STPmid, and STPhigh, respectively). The remaining 10 animals were not mechanically ventilated.

Results: In animals with mild acute lung inflammation, but not in controls: (1) messenger RNA expression of interleukin-6 was higher in STPhigh (28.1 ± 13.6; mean ± SD) and STPlow (28.9 ± 16.0) versus STPmid (7.4 ± 7.5) (P < 0.05); (2) expression of the receptor for advanced glycation end-products was increased in STPhigh (3.6 ± 1.6) versus STPlow (2.3 ± 1.1) (P < 0.05); (3) alveolar edema was decreased in STPmid (0 [0 to 0]; median, Q1 to Q3) compared with STPhigh (0.8 [0.6 to 1]) (P < 0.05); and (4) expressions of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 were higher in STPlow (3.0 ± 1.8) versus STPhigh (1.2 ± 0.5) and STPmid (1.4 ± 0.7) (P < 0.05), respectively.

Conclusions: In the mild acute lung inflammation model used herein, mechanical ventilation with inspiratory-to-expiratory of 1:1 (STPmid) minimized lung damage, whereas STPhigh increased the gene expression of biological markers associated with inflammation and alveolar epithelial cell injury and STPlow increased markers of endothelial cell damage.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / blood
  • Disease Models, Animal
  • Endothelium / metabolism
  • Endothelium / physiopathology*
  • Inflammation / blood*
  • Inflammation / etiology
  • Intercellular Adhesion Molecule-1 / blood
  • Interleukin-6 / blood
  • Male
  • Pulmonary Alveoli / metabolism
  • Pulmonary Alveoli / physiopathology*
  • Rats
  • Rats, Wistar
  • Respiration, Artificial / adverse effects*
  • Respiration, Artificial / methods
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / physiopathology*
  • Stress, Physiological / physiology*
  • Time Factors
  • Vascular Cell Adhesion Molecule-1 / blood

Substances

  • Biomarkers
  • Interleukin-6
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1