• Nathane S Felix, Cynthia S Samary, Fernanda F Cruz, Nazareth N Rocha, Marcos V S Fernandes, Joana A Machado, Rebecca L Bose-Madureira, Vera L Capelozzi, Paolo Pelosi, Pedro L Silva, John J Marini, and Rocco Patricia R M PRM.
• From the Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil (N.S.F., C.S.S., F.F.C., N.N.R., M.V.S.F., J.A.M., R.L.B.-M., P.L.S., P.R.M.R.) the Department of Physiology and Pharmacology, Biomedical Institute, Fluminense Federal University, Niteroi, Brazil (N.N.R.) the Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil (V.L.C.) the Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy (P.P.) Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Martino, Genoa, Italy (P.P.) Regions Hospital and University of Minnesota, Minneapolis/Saint Paul, Minnesota (J.J.M.).
• Anesthesiology. 2019 May 1; 130 (5): 767-777.

BackgroundThis study hypothesized that, in experimental mild acute respiratory distress syndrome, lung damage caused by high tidal volume (VT) could be attenuated if VT increased slowly enough to progressively reduce mechanical heterogeneity and to allow the epithelial and endothelial cells, as well as the extracellular matrix of the lung to adapt. For this purpose, different strategies of approaching maximal VT were tested.MethodsSixty-four Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 h, animals were randomly assigned to receive mechanical ventilation with VT = 6 ml/kg for 2 h (control); VT = 6 ml/kg during hour 1 followed by an abrupt increase to VT = 22 ml/kg during hour 2 (no adaptation time); VT = 6 ml/kg during the first 30 min followed by a gradual VT increase up to 22 ml/kg for 30 min, then constant VT = 22 ml/kg during hour 2 (shorter adaptation time); and a more gradual VT increase, from 6 to 22 ml/kg during hour 1 followed by VT = 22 ml/kg during hour 2 (longer adaptation time). All animals were ventilated with positive end-expiratory pressure of 3 cm H2O. Nonventilated animals were used for molecular biology analysis.ResultsAt 2 h, diffuse alveolar damage score and heterogeneity index were greater in the longer adaptation time group than in the control and shorter adaptation time animals. Gene expression of interleukin-6 favored the shorter (median [interquartile range], 12.4 [9.1-17.8]) adaptation time compared with longer (76.7 [20.8 to 95.4]; P = 0.02) and no adaptation (65.5 [18.1 to 129.4]) time (P = 0.02) strategies. Amphiregulin, metalloproteinase-9, club cell secretory protein-16, and syndecan showed similar behavior.ConclusionsIn experimental mild acute respiratory distress syndrome, lung damage in the shorter adaptation time group compared with the no adaptation time group was attenuated in a time-dependent fashion by preemptive adaptation of the alveolar epithelial cells and extracellular matrix. Extending the adaptation period increased cumulative power and did not prevent lung damage, because it may have exposed animals to injurious strain earlier and for a longer time, thereby negating any adaptive benefit.

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