Species-specific effects of positive end-expiratory pressure on diaphragm and chest wall geometry in mice, rats, and humans

In critically ill mechanically ventilated patients, positive end-expiratory pressure (PEEP) is applied to limit alveolar collapse. However, PEEP will also affect diaphragm geometry and function. Various animal models are used to study the effects of mechanical ventilation on the diaphragm, but chest wall mechanics may influence diaphragm responses to PEEP. We hypothesized that interspecies differences are relevant when studying the effect of PEEP on diaphragm geometry during mechanical ventilation. Specifically, the chest wall compliance, which varies among species, may be an important determinant of the effect of PEEP on diaphragm geometry and function. This is relevant in future studies into diaphragm adaptations during PEEP and particularly in genetically engineered animal models. Using magnetic resonance imaging (MRI), we studied the effect of PEEP on diaphragm surface and thorax geometry in ventilated mice, rats, and healthy volunteers. PEEP reduced diaphragm surface in mice, rats, and humans, but the effect was smaller in mice compared with rats. This difference was not attributable to disparities in lung compliance or chest wall compliance. Compared with healthy volunteers, rats showed a larger decrease in diaphragm surface due to greater caudal displacement, whereas mice showed a similar decrease in diaphragm surface, but with more thoracic widening. These findings indicate that the effect of PEEP on diaphragm geometry is influenced by chest wall movement and varies across species. These findings are critical for interpreting diaphragm adaptations to mechanical ventilation in both animal models and patients.