Comparative Effects of Volutrauma and Atelectrauma on Lung Inflammation in Experimental Acute Respiratory Distress Syndrome

Abstract

Objective: Volutrauma and atelectrauma promote ventilator-induced lung injury, but their relative contribution to inflammation in ventilator-induced lung injury is not well established. The aim of this study was to determine the impact of volutrauma and atelectrauma on the distribution of lung inflammation in experimental acute respiratory distress syndrome.

Design: Laboratory investigation.

Setting: University-hospital research facility.

Subjects: Ten pigs (five per group; 34.7-49.9 kg)

Interventions: : Animals were anesthetized and intubated, and saline lung lavage was performed. Lungs were separated with a double-lumen tube. Following lung recruitment and decremental positive end-expiratory pressure trial, animals were randomly assigned to 4 hours of ventilation of the left (ventilator-induced lung injury) lung with tidal volume of approximately 3 mL/kg and 1) high positive end-expiratory pressure set above the level where dynamic compliance increased more than 5% during positive end-expiratory pressure trial (volutrauma); or 2) low positive end-expiratory pressure to achieve driving pressure comparable with volutrauma (atelectrauma). The right (control) lung was kept on continuous positive airway pressure of 20 cm H2O, and CO2 was partially removed extracorporeally.

Measurements and main results: Regional lung aeration, specific [F]fluorodeoxyglucose uptake rate, and perfusion were assessed using computed and positron emission tomography. Volutrauma yielded higher [F]fluorodeoxyglucose uptake rate in the ventilated lung compared with atelectrauma (median [interquartile range], 0.017 [0.014-0.025] vs 0.013 min [0.010-0.014 min]; p < 0.01), mainly in central lung regions. Volutrauma yielded higher [F]fluorodeoxyglucose uptake rate in ventilator-induced lung injury versus control lung (0.017 [0.014-0.025] vs 0.011 min [0.010-0.016 min]; p < 0.05), whereas atelectrauma did not. Volutrauma decreased blood fraction at similar perfusion and increased normally as well as hyperaerated lung compartments and tidal hyperaeration. Atelectrauma yielded higher poorly and nonaerated lung compartments, and tidal recruitment. Driving pressure increased in atelectrauma.

Conclusions: In this model of acute respiratory distress syndrome, volutrauma promoted higher lung inflammation than atelectrauma at comparable low tidal volume and lower driving pressure, suggesting that static stress and strain are major determinants of ventilator-induced lung injury.

Figure 1

Time course of interventions. ARDS = acute respiratory distress syndrome, CPAP = continuous positive airway pressure, DLT = double-lumen endotracheal tube, ILA = interventional lung assist, PEEP = positive end-expiratory pressure, PRVC = pressure-regulated volume-controlled ventilation, VCV = volume-controlled ventilation, V_T = tidal volume.

Figure 2

Three-dimensional illustration of the distributions of aeration and single-slice images of gas fraction, perfusion, and [¹⁸F]-fluorodeoxyglucose uptake rate (K_i) of representative animals. Three-dimensional illustration of the distribution of aeration, as well as 2D slice images of the gas fraction (F_GAS), perfusion, and [¹⁸F]-fluorodeoxyglucose uptake rate (K_{i P}, computed voxel by voxel using Patlak method, and normalized to [1 – F_GAS]) in representative animals of the volutrauma (upper) and atelectrauma groups (lower), respectively. Two-dimensional slice images represent the maximal cross-sectional areas of the respective slice in the whole lung images. Horizontal color bars denote the respective scales. Hyper = hyperaerated compartment, L = left VILI (ventilated) lung, non = nonaerated compartment, normal = normally aerated compartment, poor = poorly aerated compartment, R = right control (nonventilated) lung.

Figure 3

[¹⁸F]-fluorodeoxyglucose uptake rate (K_i) of the ventilator-induced lung injury (VILI) and control lung grouped by injury model. Specific K_i (K_iS) of the VILI lung (black triangles, ventilated lung) and corresponding control lung (gray squares, nonventilated lung) of all animals of the volutrauma group (left) and atelectrauma group (right). *p < 0.05 (vs nonventilated control lung, same injury model). #p < 0.05 (vs ventilated VILI atelectrauma lung). ##p < 0.01 (vs ventilated VILI atelectrauma lung).

Figure 4

Regional specific [¹⁸F]-fluorodeoxyglucose net uptake rate (K_iS), gas fraction (F_GAS), blood fraction (F_BLOOD), and perfusion grouped by injury model. Median and interquartile range of the K_iS, F_GAS, F_BLOOD, and perfusion in five adjacent regions of the same lung mass reaching from ventral (regions of interest [ROI] 1) to dorsal (ROI 5) for the ventilator-induced lung injury (VILI) (black triangles, ventilated lung) and control lung (gray squares, nonventilated lung) of all animals of the volutrauma (left) and atelectrauma groups (right). *p < 0.05 (vs nonventilated control lung in same ROI, same injury model), #p < 0.05 (vs ventilated VILI atelectrauma lung in same ROI).

Figure 5

Regional distribution of aeration compartments at end-inspiration and end-expiration grouped by injury model. Mean and SE of the distributions of hyperaerated (white), normally aerated (dark gray), poorly aerated (light gray), and nonaerated compartments (black) of ventilated ventilator-induced lung injury lungs in volutrauma (left) and atelectrauma groups (right), respectively, for five adjacent regions of the same lung mass reaching from ventral (regions of interest [ROI] 1) to dorsal (ROI 5) at end-expiration and end-inspiration, expressed as percent mass (%mass). #p < 0.05 (atelectrauma vs volutrauma for same aeration compartment in same ROI at the same lung volume). No significant difference of aeration compartments between ROIs at the same lung volume within groups.

Figure 6

Regional distribution of tidal recruitment and tidal hyperaeration. Median and interquartile range of the amount of tidal recruitment (left) and tidal hyperaeration (right) of ventilated ventilator-induced lung injury lungs in volutrauma (gray) and atelectrauma (black) groups, respectively, in five adjacent regions of the same lung mass reaching from ventral (regions of interest [ROI] 1) to dorsal (ROI 5). Tidal recruitment was calculated as the decrease in the percentage of mass of nonaerated compartment from end-expiration to end-inspiration. Tidal hyperaeration was calculated as the increase in the percentage of mass of hyperaeration from end-expiration to end-inspiration. Note different axis scales between panels. *p < 0.05 (tidal recruitment vs tidal hyperaeration in same ROI and injury model), #p < 0.05 (atelectrauma vs volutrauma for tidal recruitment or tidal hyperaeration, respectively, in same ROI).