title: The response to recruitment worsens with progression of lung injury and fibrin accumulation in a mouse model of acid aspiration.
abstract: Reopening the injured lung with deep inflation (DI) and positive end-expiratory pressure (PEEP) likely depends on the duration and severity of acute lung injury (ALI), key features of which include increased alveolar permeability and fibrin accumulation. We hypothesized that the response to DI and PEEP would worsen as ALI evolves and that this would correspond with increasing accumulation of alveolar fibrin. C57BL/6 mice were anesthetized and aspirated 75 microl of HCl (pH 1.8) or buffered normal saline. Subgroups were reanesthetized 4, 14, 24, and 48 h later. Following DI, tissue damping (G) and elastance (H) were measured periodically at PEEP of 1, 3, and 6 cmH(2)O, and air within the lung (thoracic gas volume) was quantified by microcomputed tomography. Following DI, G and H increased with time during progressive lung derecruitment, the latter confirmed by microcomputed tomography. The rise in H was greater in acid-injured mice than in controls (P < 0.05) and also increased from 4 to 48 h after acid aspiration, reflecting progressively worsening injury. The rise in H was reduced by PEEP, but this effect was significantly blunted by 48 h (P < 0.05), also confirmed by thoracic gas volume. Lung permeability and alveolar fibrin also increased over the 48-h study period, accompanied by increasing levels and transcription of the fibrinolysis inhibitor plasminogen activator inhibitor-1. Lung injury worsens progressively in mice during the 48 h following acid aspiration. This injury manifests as progressively increasing alveolar instability, likely due to surfactant dysfunction caused by increasing levels of alveolar protein and fibrin.
authors.affiliation: Vermont Lung Center, Department of Medicine, University of Vermont, Burlington, Vermont, USA. Gil.Allen@uvm.edu
authors.forename: Gilman B
authors.initials: GB
authors.lastname: Allen
authors.forename: Timothy
authors.initials: T
authors.lastname: Leclair
authors.forename: Mary
authors.initials: M
authors.lastname: Cloutier
authors.forename: John
authors.initials: J
authors.lastname: Thompson-Figueroa
authors.forename: Jason H T
authors.initials: JH
authors.lastname: Bates
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005342:Fibrinolysis / Q000502:physiology; D006851:Hydrochloric Acid / Q000494:pharmacology; D008176:Lung Volume Measurements; D051379:Mice; D008810:Mice, Inbred C57BL; D011015:Pneumonia, Aspiration / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D011175:Positive-Pressure Respiration; D012128:Respiratory Distress Syndrome / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D005337:Fibrin; D006851:Hydrochloric Acid