Lung injury animal models

V6. Villar, J., Edelson, J. D., Post, M., Mullen, J. B. M., and Slutsky, A. S., Induction of heat stress proteins is associated with decreased mortality in an animal model of acute lung injury. Am. Rev. Respir. Dis. 147, 177-181 (1993). 

Studies have indicated that leukocytes play a critical role in the activation of coagulation in patients with septicemia and in animal models of acute lung injury (69). One study has presented direct evidence indicating the role of tissue factor expression on activated endothelial cells on in vivo thrombogenesis (70). 

Development and validation of in vitro and/or in vivo animal models for rapid screening of molecular hbraries to identify potential medical countermeasures is another priority of the CounterACT program. These models include seizures in small mammals, models of direct lung injury from an inhaled source, animal models of cyanide intoxication, and medium throughput models of dermal or ocular injuries. It is important that models be amenable to use under GLP methodology so that the data generated are acceptable to the FDA. Since adherence to GLP standards may be expensive, earher screens to identify potential hits are usually performed under non-GLP conditions. 

In an animal model, acute lung injury was inhibited by pretreatment with clarithromycin or roxithromycin, which significantly ameliorated bleomycin-induced increases in the total cell and neutrophil counts in bronchoalveolar lavage fluids and wet lung weight (25). Pretreatment with clarithromycin or roxithromycin also suppressed inflammatory cell infiltration and interstitial lung edema. Pretreatment with azithromycin was much less effective. 

Selective inhibition of inflammatory cytokines is also an attractive approach. In animal models, antibodies to TNFa prevent lung fibrosis when given prior to injury from silica, bleomycin or antigen-induced extrinsic allergic alveolitis (Piguet etal., 1989, 1990 Denis et al., 1991). This approach may be an option in humans since TNFa antibodies have been used successfully as a therapy in patients with rheumatoid arthritis (Elliot etal., 1993). 

ARDS) ° or to the various animal models of lung injury which admittedly mimic aspects of the human conditions only incompletely. 

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