Background. Mechanical ventilation (MV) has the potential to initiate ventilator-induced lung injury (VILI). The pathogenesis of VILI has been primarily studied in animal models using more or less injurious ventilator settings. However, we speculate that duration of MV also influences severity and character of VILI. Methods. Sixty-four healthy C57Bl/6 mice were mechanically ventilated for 5 or 12 hours, using lower tidal volumes with positive end-expiratory pressure (PEEP) or higher tidal volumes without PEEP. Fifteen nonventilated mice served as controls. Results. All animals remained hemodynamically stable and survived MV protocols. In both MV groups, PaO2 to FiO2 ratios were lower and alveolar cell counts were higher after 12 hours of MV compared to 5 hours. Alveolar-capillary permeability was increased after 12 hours compared to 5 hours, although differences did not reach statistical significance. Lung levels of inflammatory mediators did not further increase over time. Only in mice ventilated with increased strain, lung compliance declined and wet to dry ratio increased after 12 hours of MV compared to 5 hours. Conclusions. Deleterious effects of MV are partly dependent on its duration. Even lower tidal volumes with PEEP may initiate aspects of VILI after 12 hours of MV. 1. Introduction Increased strain due to mechanical ventilation (MV) has the potential to aggravate existing lung injury [1]. Indeed, one meta-analysis shows intensive care unit (ICU) patients with acute respiratory distress syndrome (ARDS) to benefit from MV with lower tidal volume VT [2]. MV with too high VT even has the potential to induce lung injury [3]. This is confirmed in a more recent meta-analysis that shows patients without ARDS at onset of MV to benefit from MV with lower VT as well [4]. Importantly, this meta-analysis also showed beneficial effects of lower VT in patients receiving MV during general anesthesia for surgery [4]. The potential of MV to aggravate or initiate lung injury was originally proposed in animal models and focused merely on size of VT. Indeed, the so-called ventilator-induced lung injury (VILI) was demonstrated in models of MV in animals with injured lungs [5]. These models revealed that use of high VT worsened the proinflammatory response, disturbed alveolar fibrin turnover, and increased alveolar-capillary permeability resulting in accumulation of protein-rich edema and finally loss of pulmonary function. VILI was also observed in ventilated animals with noninjured lungs [6–10], confirming clinical studies, which suggest that conventional MV has
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