Exploring alveolar recruitability using positive end-expiratory pressure in mice overexpressing TGF-β1: a...

Area of Science:

• Pulmonary physiology
• Mechanical ventilation
• Lung injury

Background:

• Pre-injured lungs are vulnerable to ventilation-induced injury, particularly volutrauma from heterogeneous ventilation due to atelectasis.
• Positive end-expiratory pressure (PEEP) is used to recruit collapsed alveoli, but must be balanced against overdistension.

Purpose of the Study:

• To investigate the lung-protective potential of alveolar recruitment versus overdistension in pre-injured lungs.
• To determine optimal PEEP levels for mechanical ventilation in a mouse model of lung injury.

Main Methods:

• Mice received empty vector (AdCl) or adenoviral active TGF-β1 (AdTGF-β1) and underwent mechanical ventilation with descending PEEP.
• Recruitability was assessed using recruitment maneuvers and forced oscillations to measure lung elastance (H) and damping (G).
• Stereology quantified alveolar derecruitment and distension at various positive airway pressures (Pao) post-recruitment.

Main Results:

• Elevated H and G in AdTGF-β1 mice indicated increased lung injury.
• H was minimized at PEEP 5-8 cmH2O, correlating with reduced septal folding (derecruitment) at lower PEEP and reduced alveolar density (distension) at higher PEEP.
• AdTGF-β1 mice showed significant derecruitment at high Pao and increased alveolar size heterogeneity at low Pao.

Conclusions:

• Alveolar recruitment potential is high in AdTGF-β1 exposed mice.
• Optimal lung mechanics (minimized H) occurred at PEEP 5-8 cmH2O.
• PEEP of 8 cmH2O is recommended for lung-protective ventilation in this model to mitigate derecruitment and heterogeneity.