Modulation of Stress versus Time Product during Mechanical Ventilation Influences Inflammation as Well as Alveolar Epithelial and Endothelial Response in Rats. (January 2015)

• Record Type: Journal Article
• Authors: Spieth, Peter M.; Silva, Pedro L.; Garcia, Cristiane S. N. B.; Ornellas, Debora S.; Samary, Cynthia S.; Moraes, Lillian; Bentes, Maira; Morales, Marcelo M.; Kasper, Michael; Güldner, Andreas; Huhle, Robert; Koch, Thea; Pelosi, Paolo; de Abreu, Marcelo Gama; Rocco, Patricia R. M.
• Is Part Of: Anesthesiology. Volume 122:Number 1(2015)
• Publication Date: 2015-01
• Subjects: Anesthesiology -- Periodicals; Anesthetics -- Periodicals; Anesthesia -- Periodicals; 617.9605
• DOI: 10.1097/ALN.0000000000000415
• Languages: English
• ISSNs: 0003-3022

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Background:</title> <p>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 <italic>versus</italic> 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.</p> </sec> <sec> <title>Methods:</title> <p>In 46 rats, <italic>Escherichia coli</italic> 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 (STP<sub>low</sub>, STP<sub>mid</sub>, and STP<sub>high</sub>, respectively). The remaining 10 animals were not mechanically ventilated.</p> </sec> <sec> <title>Results:</title> <p>In animals with mild acute lung inflammation, but not in controls: (1) messenger RNA expression of interleukin-6 was higher in STP<sub>high</sub> (28.1 ± 13.6; mean ± SD) and STP<sub>low</sub> (28.9 ± 16.0) <italic>versus</italic> STP<sub>mid</sub> (7.4 ± 7.5) (<italic>P</italic> < 0.05); (2) expression of the receptor for advanced glycation end-products was increased in STP<sub>high</sub> (3.6 ± 1.6) <italic>versus</italic> STP<sub>low</sub> (2.3 ± 1.1) (<italic>P</italic> < 0.05); (3) alveolar edema was decreased in STP<sub>mid</sub> (0 [0 to 0]; median, Q1 to Q3) compared with STP<sub>high</sub> (0.8 [0.6 to 1]) (<italic>P</italic> < 0.05); and (4) expressions of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 were higher in STP<sub>low</sub> (3.0 ± 1.8) <italic>versus</italic> STP<sub>high</sub> (1.2 ± 0.5) and STP<sub>mid</sub> (1.4 ± 0.7) (<italic>P</italic> < 0.05), respectively.</p> </sec> <sec> <title>Conclusions:</title> <p>In the mild acute lung inflammation model used herein, mechanical ventilation with inspiratory-to-expiratory of 1:1 (STP<sub>mid</sub>) minimized lung damage, whereas STP<sub>high</sub> increased the gene expression of biological markers associated with inflammation and alveolar epithelial cell injury and STP<sub>low</sub> increased markers of endothelial cell damage.</p> </sec> </abstract>