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

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.

• Authors: Peter M Spieth, Pedro L Silva, Cristiane S N B Garcia, Debora S Ornellas, Cynthia S Samary, Lillian Moraes, Maira Bentes, Marcelo M Morales, Michael Kasper, Andreas Güldner, Robert Huhle, Thea Koch, Paolo Pelosi, Marcelo Gama de Abreu, Patricia R M Rocco
• Journal: Anesthesiology (Anesthesiology) Vol. 122 Issue 1 Pg. 106-16 (Jan 2015) ISSN: 1528-1175 [Electronic] United States
• PMID: 25141026 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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