Animal models of acute lung injury - PubMed (original) (raw)

Review

Animal models of acute lung injury

Gustavo Matute-Bello et al. Am J Physiol Lung Cell Mol Physiol. 2008 Sep.

Abstract

Acute lung injury in humans is characterized histopathologically by neutrophilic alveolitis, injury of the alveolar epithelium and endothelium, hyaline membrane formation, and microvascular thrombi. Different animal models of experimental lung injury have been used to investigate mechanisms of lung injury. Most are based on reproducing in animals known risk factors for ARDS, such as sepsis, lipid embolism secondary to bone fracture, acid aspiration, ischemia-reperfusion of pulmonary or distal vascular beds, and other clinical risks. However, none of these models fully reproduces the features of human lung injury. The goal of this review is to summarize the strengths and weaknesses of existing models of lung injury. We review the specific features of human ARDS that should be modeled in experimental lung injury and then discuss specific characteristics of animal species that may affect the pulmonary host response to noxious stimuli. We emphasize those models of lung injury that are based on reproducing risk factors for human ARDS in animals and discuss the advantages and disadvantages of each model and the extent to which each model reproduces human ARDS. The present review will help guide investigators in the design and interpretation of animal studies of acute lung injury.

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Figures

Fig. 1.

Fig. 1.

Human ARDS. Photomicrographs from the lungs of 2 different patients with ARDS stained with H&E. The alveolar spaces are filled with a mixed mononuclear/neutrophilic infiltrate, the alveolar walls are thickened, and the septae are edematous. Note the presence of cellular debris and proteinaceous material in the air spaces (A, magnification ×200; B, ×400). In later stages, there is a fibroproliferative response with collagen deposition in the alveolar walls (arrows). Note that the alveolar epithelium has been replaced with cuboidal cells (arrowheads). Magnification in C, ×200; D, ×400.

Fig. 2.

Fig. 2.

Oleic acid model. Rabbit lungs 6 h after the onset of intravenous infusion of saline (A) or 0.1 ml·kg−1·h−1 oleic acid over 2 h (B). Note the presence of hemorrhage, hyaline membrane formation, and inflammatory infiltrates in the lungs of the rabbit treated with oleic acid. Both rabbits were mechanically ventilated for the duration of the experiment (F

i

O2 = 0.8, respiratory rate = 30 bpm, PEEP = 2 cmH2O, tidal volume = 10 cc/kg). [From Furue et al. (74).]

Fig. 3.

Fig. 3.

Comparison of selected models of acute lung injury (ALI). A and B: normal mouse lungs. The alveolar walls are very thin, and the majority of the alveoli contain no cells (magnification in A, ×100; B, ×400). C and D: lungs from a mouse euthanized 18 h after intratracheal instillation of 5 ng/g LPS. Note the patchy nature of the injury (C, ×100) and the presence of inflammatory infiltrates and vascular congestion (D, ×400). E and F: lungs from a rabbit euthanized 2 h after exposure to mechanical ventilation with Tv = 25 cc/kg, PEEP = 2.5 cmH2O, F

i

O2 = 0.5, and RR = 20 bpm. Note the presence of intra-alveolar neutrophilic infiltrates and the deposition of hyaline membranes (E, ×200; F, ×630). G and H: lungs from a mouse euthanized 21 days after the administration of intratracheal bleomycin. Note the presence of fibrotic areas (arrows) (G, ×200; H, ×400). I and J: lungs from a mouse euthanized 12 h after aerosolization of Escherichia coli, 1 × 108 cfu/ml. Note diffuse thickening of the alveolar spaces and intra-alveolar neutrophilic infiltrates (I, ×200; J, ×400). Hematoxylin and eosin.

Fig. 4.

Fig. 4.

Acid aspiration model. Lung tissue sections from a normal mouse (left) and a mouse euthanized 2 h after intratracheal instillation of 1 M HCl, 2 μl/g (pH = 1.5) (right). Note the presence of intra-alveolar proteinaceous deposits (arrow). [From Zarbock et al. (251).]

Fig. 5.

Fig. 5.

Cecal ligation and puncture (CLP). Lungs from mice following sham surgery (left) or from mice subjected to 90 min of hemorrhagic shock (MAP = 30 mmHg) followed 24 h later by CLP (right). The lungs were stained for neutrophil-specific esterase (red). [From Lomas-Neira et al. (128).]

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