Summary
Background and objective: We evaluated the effect of duration of mechanical ventilation with different tidal volumes (VT) on ventilator-induced lung injury in healthy rats. Methods: Anaesthetized rats were ventilated with VT between 9 and 45 mL kg−1 for 1 or 7 h with a positive end-expiratory pressure of 2.5 cmH2O. Results: After 1 h, rats ventilated even with the highest applied VT (36 and 45 mL kg−1, resulting in average peak airway pressures of 30 ± 3 and 37 ± 4 cmH2O), had no detectable alterations in dynamic or static lung mechanics, gas exchange or pulmonary permeability, but a moderate degree of lung inflammation (neutrophil accumulation in broncho-alveolar lavage) observed in all groups. In contrast, after 3 h of ventilation, rats ventilated with the highest VT (36 and 45 mL kg−1) died from progressive circulatory failure and high-permeability pulmonary oedema, manifested by hypoxaemia, an increased alveolar–arterial protein concentration ratio and a reduced static lung compliance (mortality rate at 7 h, 62.5% and 100%). Animals with lower VT all survived and presented no changes in the measured variables. Conclusion: These results in normal rats demonstrate the preponderant effect of the duration (>3 h) of ‘aggressive’ ventilation and the cut-off value of the level of VT applied (>27 mL kg−1).