Editors' ChoiceCRITICAL CARE MEDICINE

Too Much of a Good Thing: Hyperoxia and Lung Injury

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Science Translational Medicine  11 Jul 2012:
Vol. 4, Issue 142, pp. 142ec123
DOI: 10.1126/scitranslmed.3004564

When you cannot breathe, nothing else matters. But sometimes you can have too much of a good thing. Even oxygen in excess can have serious negative consequences. Patients with severe hypoxic respiratory failure due to acute lung injury—or its severest form, acute respiratory distress syndrome—are mechanically ventilated with high oxygen levels (>50% inspired oxygen) as an initial treatment measure. However, this treatment combination, and even oxygen alone, has been associated with lung injury and fibrosis—conditions that are often attributed to sustained high levels of inspired oxygen. However, the underlying mechanism of this injury remains unknown.

Roan et al. hypothesized that hyperoxia alters the mechanical properties of alveolar epithelial cells (AECs), causing them to resist normal deformation leading to mechanical ventilator-induced injury. They used atomic force microscopy to measure the mechanical properties of cultured AECs with and without hyperoxia. They used a mouse alveolar epithelial cell line (MLE-12) and primary rat alveolar type II (ATII) epithelial cells for their investigations. The primary finding is that exposure to hyperoxic conditions (80 to 90% O2) for 24 or 48 hours significantly increased the “elastic modulus” (a validated measure of resistance to cellular deformation). Hyperoxia also induced remodeling of actin and microtubules in both cell types. Disruption of F-actin with cytochalasin D reduced elastic modulus in hyperoxia-treated cells to the level of normoxia-treated control cells, suggesting that F-actin mediates the hyperoxia-induced structural changes that contribute to cells’ mechanical responses. Cells with increased resistance to deformation had increased stretch-induced mechanical stress near the cell perimeter. Moreover, 20% cyclic stretching of hyperoxia-treated cells induced significant cell detachment, which is a marker of cell injury and loss of function.

Although this is an in vitro study, it sheds light on a potential underlying mechanism for increased epithelial injury during mechanical ventilation with hyperoxia. Despite the oversimplified model, this work may lead to in vivo models to evaluate this proposed mechanism, perhaps leading to novel therapies directed at lung resident cells and focused on alveolar cell structural consequences.

Truly, when you cannot breathe nothing else matters. However, supraphysiological levels of oxygen (in the setting of mechanical ventilation) can lead to permanent lung injury and sometimes death. If such a mechanism exists in the intact animal, then therapies targeted at “fluidizing” the lung alveolar epithelium may mitigate the injury caused by the very treatment intended to save lives.

E. Roan et al., Hyperoxia alters the mechanical properties of alveolar epithelial cells. Am. J. Physiol. Lung Cell. Mol. Physiol., 30 March 2012 (10.1152/ajplung.00223.2011). [Abstract]

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