Published ahead of print on May 13, 2005, doi:10.1164/rccm.200503-343OC Am. J. Respir. Crit. Care Med., Volume 172, Number 3, August 2005, 344-351 A more recent version of this article appeared on August 1, 2005
Submitted on March 4, 2005 Physiologic, Biochemical, and Imaging Characterization of Acute Lung Injury in MiceZhaohui Zhou1,1 Departments of Internal Medicine and Radiology, Washington University School of Medicine and the Mallinckrodt Institute of Radiology, St. Louis, MO, United States * To whom correspondence should be addressed. E-mail: daniel.schuster{at}wustl.edu.
Rationale: most models of acute lung injury in mice have yet to be fully characterized. Objectives: to directly compare and contrast endotoxin and oleic acid models of acute lung injury in mice in terms of their physiologic, biochemical, histopathologic, and imaging manifestations. Methods: survival studies, lung weights, xray computed tomographic scanning, light and electron microscopy, bronchoalveolar lavage, lung uptake of [18F]fluorodeoxyglucose, tissue myeloperoxidase, arterial blood gases, mean arterial pressure, and lung tissue prostanoids were measured in separate groups of C57Bl/6 mice (Normals, Endotoxin only (20 µg/gm), Oleic Acid only (0.15 µL/gm), or Endotoxin + Oleic Acid). Results: endotoxin alone caused only mild pulmonary neutrophilic inflammation with little functional or structural damage to the alveolar architecture. In contrast, oleic acid caused severe alveolar damage with the development of alveolar edema of the increased-permeability type with associated abnormalities in gas exchange. When given together, endotoxin and oleic acid acted synergistically to increase pulmonary edema and to worsen gas exchange and hemodynamics, thereby increasing mortality. This synergism was significantly attenuated by the prior administration of the endotoxin antagonist E5564 (eritoran). Conclusions: under the conditions of these studies, only mice exposed to oleic acid showed both structural and functional characteristics of acute lung injury. Nevertheless, endotoxin had potent synergistic physiologic effects that increased mortality. Overall, these models, which can be translated to genetically altered mice, are amenable to study with state-of-the-art imaging techniques, and with experimental interventions that can probe the underlying mechanisms of injury. Key words: respiratory distress syndrome (adult), positron-emission tomography, fluorodeoxyglucose F18, mice
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