title: Biological Impact of Transpulmonary Driving Pressure in Experimental Acute Respiratory Distress Syndrome.
abstract: BACKGROUND
  Ventilator-induced lung injury has been attributed to the interaction of several factors: tidal volume (VT), positive end-expiratory pressure (PEEP), transpulmonary driving pressure (difference between transpulmonary pressure at end-inspiration and end-expiration, ΔP,L), and respiratory system plateau pressure (Pplat,rs).
  
  
  METHODS
  Forty-eight Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 h, animals were randomized into combinations of VT and PEEP, yielding three different ΔP,L levels: ΔP,LLOW (VT = 6 ml/kg, PEEP = 3 cm H2O); ΔP,LMEAN (VT = 13 ml/kg, PEEP = 3 cm H2O or VT = 6 ml/kg, PEEP = 9.5 cm H2O); and ΔP,LHIGH (VT = 22 ml/kg, PEEP = 3 cm H2O or VT = 6 ml/kg, PEEP = 11 cm H2O). In other groups, at low VT, PEEP was adjusted to obtain a Pplat,rs similar to that achieved with ΔP,LMEAN and ΔP,LHIGH at high VT.
  
  
  RESULTS
  At ΔP,LLOW, expressions of interleukin (IL)-6, receptor for advanced glycation end products (RAGE), and amphiregulin were reduced, despite morphometric evidence of alveolar collapse. At ΔP,LHIGH (VT = 6 ml/kg and PEEP = 11 cm H2O), lungs were fully open and IL-6 and RAGE were reduced compared with ΔP,LMEAN (27.4 ± 12.9 vs. 41.6 ± 14.1 and 0.6 ± 0.2 vs. 1.4 ± 0.3, respectively), despite increased hyperinflation and amphiregulin expression. At ΔP,LMEAN (VT = 6 ml/kg and PEEP = 9.5 cm H2O), when PEEP was not high enough to keep lungs open, IL-6, RAGE, and amphiregulin expression increased compared with ΔP,LLOW (41.6 ± 14.1 vs. 9.0 ± 9.8, 1.4 ± 0.3 vs. 0.6 ± 0.2, and 6.7 ± 0.8 vs. 2.2 ± 1.0, respectively). At Pplat,rs similar to that achieved with ΔP,LMEAN and ΔP,LHIGH, higher VT and lower PEEP reduced IL-6 and RAGE expression.
  
  
  CONCLUSIONS
  In the acute respiratory distress syndrome model used in this experiment, two strategies minimized ventilator-induced lung injury: (1) low VT and PEEP, yielding low ΔP,L and Pplat,rs; and (2) low VT associated with a PEEP level sufficient to keep the lungs open.
authors.affiliation: From the Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil (C.S.S., R.S.S., C.L.S., N.S.F., M.B., C.S.N.B.G., P.L.S., P.R.M.R.); Laboratory of Experimental Surgery, Faculty of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil (C.L.S.); Radiology Department, National Center of Structural Biology and Image, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil (T.B., S.A.L.S.); Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil (V.L.C.); Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil (M.M.M.); Rio de Janeiro Federal Institute of Education, Science and Technology, Rio de Janeiro, Brazil (C.S.N.B.G.); University of Minnesota, Minneapolis/Regions Hospital, Pulmonary and Critical Care Medicine, St. Paul, Minnesota (J.J.M.); Pulmonary Engineering Group, Department of Anesthesiology and Intensive Care Therapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany (M.G.d.A.); and IRCCS AOU San Martino-IST, Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy (P.P.).
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Samary
authors.forename: Raquel S
authors.initials: RS
authors.lastname: Santos
authors.forename: Cíntia L
authors.initials: CL
authors.lastname: Santos
authors.forename: Nathane S
authors.initials: NS
authors.lastname: Felix
authors.forename: Maira
authors.initials: M
authors.lastname: Bentes
authors.forename: Thiago
authors.initials: T
authors.lastname: Barboza
authors.forename: Vera L
authors.initials: VL
authors.lastname: Capelozzi
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Morales
authors.forename: Cristiane S N B
authors.initials: CS
authors.lastname: Garcia
authors.forename: Sergio A L
authors.initials: SA
authors.lastname: Souza
authors.forename: John J
authors.initials: JJ
authors.lastname: Marini
authors.forename: Marcelo
authors.initials: M
authors.lastname: Gama de Abreu
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Silva
authors.forename: Paolo
authors.initials: P
authors.lastname: Pelosi
authors.forename: Patricia R M
authors.initials: PR
authors.lastname: Rocco
mesh_terms: D000818:Animals; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism*; D008297:Male; D011175:Positive-Pressure Respiration / Q000009:adverse effects* / Q000379:methods; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D015656:Respiratory Mechanics / Q000502:physiology*; D013990:Tidal Volume / Q000502:physiology*
chemical_list: D018836:Inflammation Mediators