Chlorine gas induced acute lung injury in isolated rabbit lung

Ménaouar, Ahmed; Anglade, Daniel; Baussand, P; Pelloux, A; Corboz, Michel R.; Lantuéjoul, Sylvie; Benchetrit, Gila; Grimbert, FA

doi:10.1183/09031936.97.10051100

Cited by 24 publications

(12 citation statements)

References 24 publications

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“…The rabbit model described here overcomes some limitations of previously developed non-rodent models. Studies utilizing rabbit models to investigate chlorine inhalation have either used one rabbit per time point per dose with the evaluation of only limited endpoints (Barrow and Smith, 1975), or used isolated rabbit lungs, which cannot be used to study the long-term effects of chlorine (Menaouar et al, 1997). In most other non-rodent models of chlorine inhalation, only acute effects could be evaluated, as animals were not removed from mechanical ventilation following chlorine exposure (Gunnarsson et al, 1998; Batchinsky et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Acute lung injury and persistent small airway disease in a rabbit model of chlorine inhalation

Musah

Schlueter

Humphrey

et al. 2017

Toxicology and Applied Pharmacology

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Chlorine is a pulmonary toxicant to which humans can be exposed through accidents or intentional releases. Acute effects of chlorine inhalation in humans and animal models have been well characterized, but less is known about persistent effects of acute, high-level chlorine exposures. In particular, animal models that reproduce the long-term effects suggested to occur in humans are lacking. Here, we report the development of a rabbit model in which both acute and persistent effects of chlorine inhalation can be assessed. Male New Zealand White rabbits were exposed to chlorine while the lungs were mechanically ventilated. After chlorine exposure, the rabbits were extubated and were allowed to survive for up to 24 h after exposure to 800 ppm chlorine for 4 min to study acute effects or up to 7 days after exposure to 400 ppm for 8 min to study longer term effects. Acute effects observed 6 or 24 h after inhalation of 800 ppm chlorine for 4 min included hypoxemia, pulmonary edema, airway epithelial injury, inflammation, altered baseline lung mechanics, and airway hyperreactivity to inhaled methacholine. Seven days after recovery from inhalation of 400 ppm chlorine for 8 min, rabbits exhibited mild hypoxemia, increased area of pressure-volume loops, and airway hyperreactivity. Lung histology 7 days after chlorine exposure revealed abnormalities in the small airways, including inflammation and sporadic bronchiolitis obliterans lesions. Immunostaining showed a paucity of club and ciliated cells in the epithelium at these sites. These results suggest that small airway disease may be an important component of persistent respiratory abnormalities that occur following acute chlorine exposure. This non-rodent chlorine exposure model should prove useful for studying persistent effects of acute chlorine exposure and for assessing efficacy of countermeasures for chlorine-induced lung injury.

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Section: Discussionmentioning

confidence: 99%

Acute lung injury and persistent small airway disease in a rabbit model of chlorine inhalation

Musah

Schlueter

Humphrey

et al. 2017

Toxicology and Applied Pharmacology

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“…Isolated rabbit lungs that were exposed to 500 ppm chlorine demonstrated that alveolar edema could be explained in terms of epithelial injury (44). Moreover, chlorine was suggested to compound lung injury and edema by increasing microvascular permeability (44). Previous studies showed that the post-exposure administration of a b2-agonist decreases chlorine-induced airway hyperreactivity in mice (21) by increasing lung cyclic adenosine monophosphate content, depleted after exposure to chlorine.…”

Section: Discussionmentioning

confidence: 99%

“…A 3-month observation of rats exposed to 1,500 ppm chlorine for 5 minutes showed epithelial flattening, necrosis, smooth muscle mass elevation, and an increase in the number of neutrophils in BALF (43). Isolated rabbit lungs that were exposed to 500 ppm chlorine demonstrated that alveolar edema could be explained in terms of epithelial injury (44). Moreover, chlorine was suggested to compound lung injury and edema by increasing microvascular permeability (44).…”

Section: Discussionmentioning

confidence: 99%

Post-Exposure Antioxidant Treatment in Rats Decreases Airway Hyperplasia and Hyperreactivity Due to Chlorine Inhalation

Fanucchi¹,

Bracher

Doran

et al. 2012

Am J Respir Cell Mol Biol

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We assessed the safety and efficacy of combined intravenous and aerosolized antioxidant administration to attenuate chlorine gasinduced airway alterations when administered after exposure. Adult male Sprague-Dawley rats were exposed to air or 400 parts per million (ppm) chlorine (a concentration likely to be encountered in the vicinity of industrial accidents) in environmental chambers for 30 minutes, and returned to room air, and they then received a single intravenous injection of ascorbic acid and deferoxamine or saline. At 1 hour and 15 hours after chlorine exposure, the rats were treated with aerosolized ascorbate and deferoxamine or vehicle. Lung antioxidant profiles, plasma ascorbate concentrations, airway morphology, and airway reactivity were evaluated at 24 hours and 7 days after chlorine exposure. At 24 hours after exposure, chlorine-exposed rats had significantly lower pulmonary ascorbate and reduced glutathione concentrations. Treatment with antioxidants restored depleted ascorbate in lungs and plasma. At 7 days after exposure, in chlorineexposed, vehicle-treated rats, the thickness of the proximal airways was 60% greater than in control rats, with twice the amount of mucosubstances. Airway resistance in response to methacholine challenge was also significantly elevated. Combined treatment with intravenous and aerosolized antioxidants restored airway morphology, the amount of airway mucosubstances, and airway reactivity to control levels by 7 days after chlorine exposure. Our results demonstrate for the first time, to the best of our knowledge, that severe injury to major airways in rats exposed to chlorine, as characterized by epithelial hyperplasia, mucus accumulation, and airway hyperreactivity, can be reversed in a safe and efficacious manner by the postexposure administration of ascorbate and deferoxamine.Keywords: epithelial injury; epithelial repair; mucosubstances; ascorbate; deferoxamine; aerosol Chlorine is essential to global industry and to global public health. According to the World Chlorine Council (http://www. worldchlorine.org), 14.4 million metric tons were produced in North America in 2008, and 62.8 million metric tons were produced globally. Water treatment makes up only 5% of the world's use of chlorine. The majority of chlorine is used in the production of plastics such as polyvinyl chloride (1). It is also used as a bleaching agent for pulp and paper production, as feedstock in the production of chlorinated solvents used in metalworking, in dry cleaning, in electronics, and in pharmaceutical production (1-6).Only 20 American states contain facilities that produce chlorine, but every American state has facilities that use chlorine. This results in the shipping of chlorine by railcar, and increases the potential for large-scale accidents. According to the Environmental Protection Agency, chlorine gas was related to 518 serious accidents over a 5-year period during the 1990s (1). Multiple-casualty exposures to chlorine have resulted from industrial accidents involving chlorine ta...

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“…The exposure of isolated blood-perfused rabbit lung to 500 ppm of chlorine for 10 minutes leads to an increase in microvascular permeability, reflected in an increase in fluid filtration rate and filtration coefficient (43). In intact pigs there is a rise in circulating endothelin-1 levels after chlorine exposure, and the increase in pulmonary vascular resistance associated with the exposure is reversed by an endothelin antagonist (44).…”

Section: Animal Models Of Chlorine-induced Lung Injurymentioning

confidence: 99%

Chlorine Gas Inhalation: Human Clinical Evidence of Toxicity and Experience in Animal Models

White¹,

Martin²

2010

Proceedings of the American Thoracic Society

273

211

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Chlorine gas induced acute lung injury in isolated rabbit lung

Cited by 24 publications

References 24 publications

Acute lung injury and persistent small airway disease in a rabbit model of chlorine inhalation

Acute lung injury and persistent small airway disease in a rabbit model of chlorine inhalation

Post-Exposure Antioxidant Treatment in Rats Decreases Airway Hyperplasia and Hyperreactivity Due to Chlorine Inhalation

Chlorine Gas Inhalation: Human Clinical Evidence of Toxicity and Experience in Animal Models

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