Beating the Clock in Ventilator-induced Lung Injury

Wilcox and Maas discuss the study by Felten and colleagues which tested the hypothesis that ventilator-induced lung injury (VILI) is a clock-dependent phenomenon. Investigators entrained mice in a 12 hour:12 hour light:dark cycle. Rodents are typically nocturnal mammals, as compared with diurnal humans, although strain-specific patterns are not always restricted to the dark (i.e., active phase). Once entrained, mice were subjected to varying degrees of injurious mechanical ventilation at either the beginning of the rest (dawn) or the active phase (dusk) of the circadian rhythm. They observed greater lung injury from exposures occurring during the rest phase of the circadian cycle. The differential harm was observed histologically in neutrophil recruitment, barrier permeability, inflammatory cytokine production, and hyaline membrane structure. Most importantly, there were measurable functional differences in lung compliance, inspiratory capacity, and lung permeability, resulting in more impaired oxygenation.