title: 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.affiliation: From the Pulmonary Engineering Group, Department of Anesthesiology and Intensive Care Therapy, University Hospital Carl Gustav Carus, Dresden, Technische Universität Dresden, Dresden, Germany (P.M.S., A.G., R.H., T.K., M.G.d.A.); Laboratory of Pulmonary Investigation (P.L.S., C.S.N.B.G., D.S.O., C.S.S., L.M., M.B., P.R.M.R.), and Laboratory of Cellular and Molecular Biology (M.M.M.), Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Rio de Janeiro Federal Institute of Education, Science and Technology, Rio de Janeiro, Brazil (C.S.N.B.G.); Institute of Anatomy, Technical University Dresden, Dresden, Germany (M.K.); and IRCCS AOU San Martino-IST, Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy (P.P.).
authors.forename: Peter M
authors.initials: PM
authors.lastname: Spieth
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Silva
authors.forename: Cristiane S N B
authors.initials: CS
authors.lastname: Garcia
authors.forename: Debora S
authors.initials: DS
authors.lastname: Ornellas
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Samary
authors.forename: Lillian
authors.initials: L
authors.lastname: Moraes
authors.forename: Maira
authors.initials: M
authors.lastname: Bentes
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Morales
authors.forename: Michael
authors.initials: M
authors.lastname: Kasper
authors.forename: Andreas
authors.initials: A
authors.lastname: Güldner
authors.forename: Robert
authors.initials: R
authors.lastname: Huhle
authors.forename: Thea
authors.initials: T
authors.lastname: Koch
authors.forename: Paolo
authors.initials: P
authors.lastname: Pelosi
authors.forename: Marcelo Gama
authors.initials: MG
authors.lastname: de Abreu
authors.forename: Patricia R M
authors.initials: PR
authors.lastname: Rocco
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D004727:Endothelium / Q000378:metabolism / Q000503:physiopathology*; D007249:Inflammation / Q000097:blood* / Q000209:etiology; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012121:Respiration, Artificial / Q000009:adverse effects* / Q000379:methods; D020545:Respiratory Mucosa / Q000378:metabolism / Q000503:physiopathology*; D013312:Stress, Physiological / Q000502:physiology*; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1