The link between regional tidal stretch and lung injury during mechanical ventilation

The aim of this study was to assess the association between regional tidal volume (Vt), regional functional residual capacity (FRC), and the expression of genes linked with ventilator-induced lung injury. Two groups of BALB/c mice (n = 8 per group) were ventilated for 2 hours using a protective or injurious ventilation strategy, with free-breathing mice used as control animals. Regional Vt and FRC of the ventilated mice was determined by analysis of high-resolution four-dimensional computed tomographic images taken at baseline and after 2 hours of ventilation and corrected for the volume of the region (i.e., specific [s]Vt and specific [s]FRC). RNA concentrations of 21 genes in 10 different lung regions were quantified using a quantitative PCR array. sFRC at baseline varied regionally, independent of ventilation strategy, whereas sVt varied regionally depending on ventilation strategy. The expression of IL-6 (P = 0.04), Ccl2 (P < 0.01), and Ang-2 (P < 0.05) was associated with sVt but not sFRC. The expression of seven other genes varied regionally (IL-1β and RAGE [receptor for advanced glycation end products]) or depended on ventilation strategy (Nfe2l2 [nuclear factor erythroid-derived 2 factor 2], c-fos, and Wnt1) or both (TNF-α and Cxcl2), but it was not associated with regional sFRC or sVt. These observations suggest that regional inflammatory responses to mechanical ventilation are driven primarily by tidal stretch

Effect of frequency on expansion activity.

<p>A) Effect of frequency on expansion activity normalised to the activity at 1 Hz for each animal to account for inter-animal effects. Each animal is marked by a different symbol. Overall we see a decrease in the magnitude of expansion activity for each respiration cycle as the ventilation frequency is increased. B) Expansion maps showing the effect of ventilation rate on activity of the lung throughout the ventilation cycle. As the ventilation rate is increased it can be seen that the expansion activity decreases. Expansion maps shown have over 1000 measurement locations in each map. Expansion activity, as shown here, is a dimensionless quantity.</p

Temporal measurement of lung activity via traditional methods and the X-ray velocimetry technique.

<p>A) Time plots showing the tidal volume delivered as measured with a flowmeter and X-ray velocimetry integrated expansion. The X-ray velocimetry integrated expansion was calibrated to volume according to the method of Fouras et. al <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048122#pone.0048122-Fouras3" target="_blank">[52]</a>. The coefficient of determination between the flowmeter and the X-ray velocimetry volume was &gt;0.96. The animal was being ventilated at PEEP of 9 cmH2O, PIP of 21 cmH2O and a frequency of 1 Hz. B) X-ray velocimetry integrated expansion maps calculated from the end expiration to early inspiration (i), mid-inspiration (ii) and end-inspiration (iii). The X-ray velocimetry integrated expansion maps correlate to the time indicated by the (x) symbols on the X-ray velocimetry time plot in A). It can clearly be seen that as inspiration progresses a greater amount of lung tissue expansion has occurred and the expansion maps are able to show where the changes have occurred with high spatial resolution.</p

Spatial standard deviation of expansion plotted against ventilation frequency.

<p>Spatial standard deviation of expansion activity plotted against ventilator frequency, normalised by the value at 1 Hz for each animal to account for inter-animal effects. There is a decrease in expansion activity variation as the rate of ventilation is increased. Values for the 5 animals are shown and are normalised to the 1 Hz value to minimize inter-animal effects. Each animal is marked by a different symbol. A higher degree of spatial variation of expansion at lower frequencies suggests that with a longer time available for gas flow the distribution of expansion is primarily dependant on the local lung compliance. At the higher frequencies, with a limited time for expansion to occur, the expansion activity is more consistent across the lung as shown by a smaller standard deviation in the activity.</p