• Pedro Leme Silva, Fernanda Ferreira Cruz, SamaryCynthia Dos SantosCDSLaboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Lillian Moraes, Raquel Ferreira de Magalhães, Marcos Vinicius de S Fernandes, Rebeca Bose, Vitor B Pelegati, Hernandes F Carvalho, Vera Luiza Capelozzi, Joshua Satalin, Louis Gatto, Penny Andrews, Nader Habashi, Gary Nieman, and RoccoPatricia R MPRMLaboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil..
• Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
• Crit. Care Med. 2018 Jun 1; 46 (6): e609-e617.

ObjectivesTo compare a time-controlled adaptive ventilation strategy, set in airway pressure release ventilation mode, versus a protective mechanical ventilation strategy in pulmonary and extrapulmonary acute respiratory distress syndrome with similar mechanical impairment.DesignAnimal study.SettingLaboratory investigation.SubjectsForty-two Wistar rats.InterventionsPulmonary acute respiratory distress syndrome and extrapulmonary acute respiratory distress syndrome were induced by instillation of Escherichia coli lipopolysaccharide intratracheally or intraperitoneally, respectively. After 24 hours, animals were randomly assigned to receive 1 hour of volume-controlled ventilation (n = 7/etiology) or time-controlled adaptive ventilation (n = 7/etiology) (tidal volume = 8 mL/kg). Time-controlled adaptive ventilation consisted of the application of continuous positive airway pressure 2 cm H2O higher than baseline respiratory system peak pressure for a time (Thigh) of 0.75-0.85 seconds. The release pressure (Plow = 0 cm H2O) was applied for a time (Tlow) of 0.11-0.18 seconds. Tlow was set to target an end-expiratory flow to peak expiratory flow ratio of 75%. Nonventilated animals (n = 7/etiology) were used for Diffuse Alveolar Damage and molecular biology markers analyses.Measurement And Main ResultsTime-controlled adaptive ventilation increased mean respiratory system pressure regardless of acute respiratory distress syndrome etiology. The Diffuse Alveolar Damage score was lower in time-controlled adaptive ventilation compared with volume-controlled ventilation in pulmonary acute respiratory distress syndrome and lower in time-controlled adaptive ventilation than nonventilated in extrapulmonary acute respiratory distress syndrome. In pulmonary acute respiratory distress syndrome, volume-controlled ventilation, but not time-controlled adaptive ventilation, increased the expression of amphiregulin, vascular cell adhesion molecule-1, and metalloproteinase-9. Collagen density was higher, whereas expression of decorin was lower in time-controlled adaptive ventilation than nonventilated, independent of acute respiratory distress syndrome etiology. In pulmonary acute respiratory distress syndrome, but not in extrapulmonary acute respiratory distress syndrome, time-controlled adaptive ventilation increased syndecan expression.ConclusionIn pulmonary acute respiratory distress syndrome, time-controlled adaptive ventilation led to more pronounced beneficial effects on expression of biomarkers related to overdistension and extracellular matrix homeostasis.

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