title: 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 (18)F-fluorodeoxyglucose ((18)F-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 (18)F-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 cmH(2)O, tidal volume adjusted to plateau pressure = 30 cmH(2)O). We used PET scans of injected (13)N-nitrogen to compute regional perfusion and ventilation and injected (18)F-FDG to calculate (18)F-FDG uptake rate. Regional aeration was quantified with transmission scans. Whole lung (18)F-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 (18)F-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. (18)F-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, (18)F-FDG uptake in normally aerated regions was low and similar between lungs. Surfactant depletion produces increased and heterogeneously distributed pulmonary (18)F-FDG uptake after 4 h of supine mechanical ventilation. Metabolic activity is highest in poorly aerated dependent regions, suggesting local increased inflammation.
authors.affiliation: Dept. of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. mvidalmelo@partners.org
authors.forename: Nicolas
authors.initials: N
authors.lastname: de Prost
authors.forename: Eduardo L
authors.initials: EL
authors.lastname: Costa
authors.forename: Tyler
authors.initials: T
authors.lastname: Wellman
authors.forename: Guido
authors.initials: G
authors.lastname: Musch
authors.forename: Tilo
authors.initials: T
authors.lastname: Winkler
authors.forename: Mauro R
authors.initials: MR
authors.lastname: Tucci
authors.forename: R Scott
authors.initials: RS
authors.lastname: Harris
authors.forename: Jose G
authors.initials: JG
authors.lastname: Venegas
authors.forename: Marcos F
authors.initials: MF
authors.lastname: Vidal Melo
mesh_terms: D000818:Animals; D018893:Bronchoalveolar Lavage / Q000379:methods; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D007249:Inflammation / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism*; D009590:Nitrogen Radioisotopes / Q000008:administration & dosage; D011175:Positive-Pressure Respiration / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods; D011663:Pulmonary Surfactants / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012121:Respiration, Artificial / Q000379:methods*; D012756:Sheep; D013314:Stress, Mechanical
chemical_list: D009590:Nitrogen Radioisotopes; D011663:Pulmonary Surfactants; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18