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Anesthesiology:
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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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.
(C) 2014 American Society of Anesthesiologists, Inc.
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