In contrast to widespread belief, several experimental studies have shown less lung injury in atelectatic areas. Tsuchida et al. [
21] investigated histological damage in lavaged rats subjected to non-injurious (with V
T 8 ml/kg and PEEP 14 cmH
2O) and injurious (V
T 25 ml/kg and PEEP 4–7 cmH
2O) mechanical ventilation. During injurious mechanical ventilation, lung injury was higher in non-dependent than in dependent lung regions. This finding was explained by the fact that injurious ventilation, and more particularly higher V
T, was distributed mainly in non-dependent lung regions with potential risk of overdistension, while dependent lung regions were relatively protected because of possible intra-alveolar edema. Interestingly, the greatest damage was observed in peripheral airways, which were likely subjected to higher stress during injurious mechanical ventilation. In line with these findings, Wakabayashi et al. [
22] investigated three different settings of mechanical ventilation in isolated, perfused lungs: 1) low V
T (7 ml/kg) with PEEP (5 cmH
2O) and regular sustained inflation; 2) high-stretch strategy consisting of high V
T (30–32 ml/kg) with PEEP (3 cmH
2O) and sustained inflation; and 3) atelectasis strategy with low tidal volume but no PEEP or sustained inflation. They found that the high-stretch strategy, but not atelectrauma (atelectasis), activated monocytes within the pulmonary vasculature, leading to cytokine release into the systemic circulation. Finally, Chu et al. [
23] ventilated ex vivo rat lungs with an opening and closing strategy without PEEP (V
T 7 ml/kg), opening and closing strategy with PEEP (V
T 7 ml/kg and PEEP 5 cmH
2O), and resting atelectasis. While the inflammatory process was more pronounced in animals ventilated with no PEEP, no differences were found between the PEEP-treated vs. resting atelectasis groups. Furthermore, the authors found that, at high volumes, cyclic stretch increased inflammatory mediators in the lungs compared to continuous stretch at a pressure equivalent to the mean airway pressure, but had no additional effect compared with continuous stretch at a pressure equal to the peak inspiratory pressure. These experimental data indicate that the degree of alveolar overdistension is a more important contributor to the release of pro-inflammatory cytokines than the cyclic nature of the ventilatory pattern. The authors suggested that “closing the lungs and keeping them closed” might be protective against VILI. These results differed from previous studies that observed increases in chemokines in the presence of overstretch of the lung, most likely because they used two-hit models, in which the lungs were injured before overstretch [
24,
25].
In conclusion, experimental evidence suggests that atelectatic-collapsed lung regions, when not subjected to repetitive opening and closing, are not characterized by more tissue inflammation.