Gradually Increasing Tidal Volume May Mitigate Experimental Lung Injury In Rats

Background: This study hypothesized that, in experimental mild acute respiratory distress syndrome, lung damage caused by high tidal volume (V T) could be attenuated if V T 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 V T were tested.Methods: Sixty-four Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 h, animals were randomly assigned to receive mechanical ventilation with V T = 6 ml/kg for 2 h (control); V T = 6 ml/kg during hour 1 followed by an abrupt increase to V T = 22 ml/kg during hour 2 (no adaptation time); V T = 6 ml/kg during the first 30 min followed by a gradual V T increase up to 22 ml/kg for 30 min, then constant V T = 22 ml/kg during hour 2 (shorter adaptation time); and a more gradual V T increase, from 6 to 22 ml/ kg during hour 1 followed by V T = 22 ml/kg during hour 2 (longer adaptation time). All animals were ventilated with positive end-expiratory pressure of 3 cm H 2 O. Nonventilated animals were used for molecular biology analysis.Results: At 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.Conclusions: In 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.