Cynthia S Samary1, Raquel S Santos, Cíntia L Santos, Nathane S Felix, Maira Bentes, Thiago Barboza, Vera L Capelozzi, Marcelo M Morales, Cristiane S N B Garcia, Sergio A L Souza, John J Marini, Marcelo Gama de Abreu, Pedro L Silva, Paolo Pelosi, Patricia R M Rocco. 1. 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.).
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. CONCLUSION: 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.
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. CONCLUSION: 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: Anna Geke Algera; Luigi Pisani; Renato Carneiro de Freitas Chaves; Thiago Chaves Amorim; Thomas Cherpanath; Rogier Determann; Dave A Dongelmans; Frederique Paulus; Pieter Roel Tuinman; Paolo Pelosi; Marcelo Gama de Abreu; Marcus J Schultz; Ary Serpa Neto Journal: Ann Transl Med Date: 2018-01
Authors: Alessandra F Thompson; Lillian Moraes; Nazareth N Rocha; Marcos V S Fernandes; Mariana A Antunes; Soraia C Abreu; Cintia L Santos; Vera L Capelozzi; Cynthia S Samary; Marcelo G de Abreu; Felipe Saddy; Paolo Pelosi; Pedro L Silva; Patricia R M Rocco Journal: PLoS One Date: 2021-08-20 Impact factor: 3.240
Authors: Ary Serpa Neto; Roberto Rabello Filho; Thomas Cherpanath; Rogier Determann; Dave A Dongelmans; Frederique Paulus; Pieter Roel Tuinman; Paolo Pelosi; Marcelo Gama de Abreu; Marcus J Schultz Journal: Ann Intensive Care Date: 2016-11-03 Impact factor: 6.925
Authors: Gisele de A Padilha; Lucas F B Horta; Lillian Moraes; Cassia L Braga; Milena V Oliveira; Cíntia L Santos; Isalira P Ramos; Marcelo M Morales; Vera Luiza Capelozzi; Regina C S Goldenberg; Marcelo Gama de Abreu; Paolo Pelosi; Pedro L Silva; Patricia R M Rocco Journal: Intensive Care Med Exp Date: 2016-10-19
Authors: Nazareth N Rocha; Cynthia S Samary; Mariana A Antunes; Milena V Oliveira; Matheus R Hemerly; Patrine S Santos; Vera L Capelozzi; Fernanda F Cruz; John J Marini; Pedro L Silva; Paolo Pelosi; Patricia R M Rocco Journal: Respir Res Date: 2021-07-30