Effects of surfactant depletion on regional pulmonary metabolic activity during mechanical ventilation

Abstract

Inflammation during mechanical ventilation is thought to depend on regional mechanical stress. This can be produced by concentration of stresses and cyclic recruitment in low-aeration dependent lung. Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) allows for noninvasive assessment of regional metabolic activity, an index of neutrophilic inflammation. We tested the hypothesis that, during mechanical ventilation, surfactant-depleted low-aeration lung regions present increased regional 18F-FDG uptake suggestive of in vivo increased regional metabolic activity and inflammation. Sheep underwent unilateral saline lung lavage and were ventilated supine for 4 h (positive end-expiratory pressure = 10 cmH2O, tidal volume adjusted to plateau pressure = 30 cmH2O). We used PET scans of injected 13N-nitrogen to compute regional perfusion and ventilation and injected 18F-FDG to calculate 18F-FDG uptake rate. Regional aeration was quantified with transmission scans. Whole lung 18F-FDG uptake was approximately two times higher in lavaged than in nonlavaged lungs (2.9 ± 0.6 vs. 1.5 ± 0.3 10−3/min; P < 0.05). The increased 18F-FDG uptake was topographically heterogeneous and highest in dependent low-aeration regions (gas fraction 10–50%, P < 0.001), even after correction for lung density and wet-to-dry lung ratios. 18F-FDG uptake in low-aeration regions of lavaged lungs was higher than that in low-aeration regions of nonlavaged lungs ( P < 0.05). This occurred despite lower perfusion and ventilation to dependent regions in lavaged than nonlavaged lungs ( P < 0.001). In contrast, 18F-FDG uptake in normally aerated regions was low and similar between lungs. Surfactant depletion produces increased and heterogeneously distributed pulmonary 18F-FDG uptake after 4 h of supine mechanical ventilation. Metabolic activity is highest in poorly aerated dependent regions, suggesting local increased inflammation.