Pulmonary atelectasis during low stretch ventilation: "open lung" versus "lung rest" strategy

Area of Science:

• Pulmonary Medicine
• Critical Care Medicine
• Cellular Biology

Background:

• Limiting tidal volume (VT) is a strategy to minimize ventilator-induced lung injury (VILI).
• Low VT ventilation can lead to atelectasis, potentially causing cell disruption and apoptosis.
• Mitogen-activated protein kinases (MAPKs) are implicated in VILI and cellular responses.

Purpose of the Study:

• To investigate the hypothesis that atelectasis influences the response to protective ventilation.
• To examine the role of MAPKs in the cellular response to different low VT ventilation strategies.
• To compare the effects of low stretch/lung rest versus low stretch/open lung strategies on VILI and cellular integrity.

Main Methods:

• Prospective randomized study in adult male mice using isolated, nonperfused lungs.
• Experimental groups included VILI (high VT), low stretch/lung rest (low VT, low PEEP), and low stretch/open lung (low VT, higher PEEP with recruitment maneuvers).
• Evaluated respiratory mechanics, lung histology, inflammatory mediators, ultrastructural cell damage via electron microscopy, apoptosis, and MAPK activation.

Main Results:

• Both low stretch strategies equally reduced VILI-induced respiratory mechanics derangement, lung histology damage, and inflammatory mediators.
• VILI caused significant pulmonary cell nuclear swelling and membrane disruption.
• Low stretch/lung rest showed more epithelial cell thickening and plasma membrane blebs compared to low stretch/open lung.
• Low stretch/lung rest had less apoptosis and caspase-3 expression but greater MAPK activation compared to low stretch/open lung.

Conclusions:

• Low stretch ventilation strategies effectively attenuate VILI.
• The low stretch/lung rest strategy, while reducing VILI, is associated with increased ultrastructural evidence of cell damage.
• This increased cell damage in the low stretch/lung rest group may be mediated through the MAPK pathway, suggesting a trade-off between VILI attenuation and cellular integrity.