We observed that, compared to modes with spontaneous breathing activity, PCV induced damage to the diaphragm. This finding is consistent with reports of several studies that have shown less diaphragmatic injury during assisted ventilation [18,19]. Sassoon selleck bio et al. showed that partial respiratory muscle activation reduces muscle dysfunction in other ALI models [20]. Nevertheless, BIVENT-50 was associated with increased diaphragm injury in ALIexp, as evidenced by augmented vacuolization, but not in ALIp. A possible explanation is that the amount of muscle work during spontaneous breath cycles was relatively low in animals with ALIexp that were ventilated with BIVENT-50, favoring diaphragmatic dysfunction. However, not only the amount of inspiratory effort but also RR per se may affect diaphragmatic injury.

These data could have a potential impact on further investigations into this specific issue and highlight the importance of monitoring and evaluating RR during assisted ventilation. Our results suggest that controlled breaths during BIVENT should be cautiously reduced in ALIexp to minimize diaphragmatic injury.Pulmonary and extrapulmonary mild ALI were induced by administering E. coli LPS intratracheally and intraperitoneally, respectively. Both models cause similar deterioration in oxygenation, lung mechanics and alveolar collapse [9,21]. The LPS model reproduces some of the main features of ALI, such as histological tissue injury, alteration of the alveolar capillary barrier, inflammation and pulmonary dysfunction [22].

Direct lung injury (ALIp) primarily affects the alveolar epithelium, with damage occurring mainly in the intra-alveolar space, with alveolar flooding and areas of consolidation [9,21]. In indirect lung injury (ALIexp), endothelial cells are the first target of damage, with a subsequent increase in vascular permeability. Thus, the main pathologic alteration due to an indirect insult may be microvessel congestion and interstitial edema, with relative sparing of intra-alveolar spaces [9]. In view of these facts, we hypothesized that BIVENT would be more effective to reopen atelectatic lung regions (thus resulting in less VALI) in ALIexp as compared to ALIp.In line with current recommendations [23], we used protective mechanical ventilation with the same driving pressure to achieve a low Vt (6 ml/kg) during both PCV and BIVENT.

The level of PEEP was set at 5 cmH2O because previous observations from our group suggested that Anacetrapib higher levels may lead to hyperinflation and lung injury in these models of ALI in rats [10,21]. Unlike other types of biphasic CPAP ventilation, BIVENT allows spontaneous breaths not only during low levels of CPAP but also during high levels. Thus, ineffective breaths are avoided during the high level of CPAP.