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doi: 10.1097/ALN.0000000000000415
Critical Care Medicine: PDF Only

Modulation of Stress versus Time Product during Mechanical Ventilation Influences Inflammation as Well as Alveolar Epithelial and Endothelial Response in Rats.

Spieth, Peter M. M.D.; Silva, Pedro L. Ph.D.; Garcia, Cristiane S. N. B. Ph.D.; Ornellas, Debora S. Ph.D.; Samary, Cynthia S. Ph.D.; Moraes, Lillian M.Sc.; Bentes, Maira R.R.T.; Morales, Marcelo M. M.D., Ph.D.; Kasper, Michael Ph.D.; Güldner, Andreas M.D.; Huhle, Robert M.Sc.; Koch, Thea M.D., Ph.D.; Pelosi, Paolo M.D.; de Abreu, Marcelo Gama M.D., Ph.D.; Rocco, Patricia R. M. M.D., Ph.D.

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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.
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