Currently, there is no direct comparison between the smoke-induced pulmonary injury in mice and rats using the same animal model to control for variables like conscious state of the rodent, endotracheal intubation, combustion material, smoke delivery mechanism, or smoke chamber. There are known variations with mouse and rat lung capacity, parenchymal tissue volume, and airway distribution, as well as variations in nasopharyngeal particle clearance and breathing patterns in awake vs. The smoke inhalation injury model is typically confirmed by parenchymal, histopathological, and immunological evaluation. To our knowledge, there are no studies that directly compare smoke-induced lung injury between these two animals using the same inhalation injury model. These animal models report a range of immune and inflammatory responses due to variation in types of rodent, injury validation, smoke exposure time, anesthesia, source of generated smoke, and the mechanism of smoke administration ( 4, 5, 7, 25, 32, 35). Historically, small animal inhalation injury models have studied either mice or rats. This has led to the use of small animals to test emerging therapeutics for smoke inhalation injury. The size of the animal, however, has led to limitations, including cost and limited cross-reactivity with numerous laboratory reagents. Sheep have commonly been used in smoke inhalation injury models as their large size allows for both closer recapitulation of human injury and similar monitoring to that seen in acute lung injury after smoke inhalation in hospital patients ( 14, 15). These animal models have included sheep, rats, and mice, all of which have limitations from a cellular and structural level based on the variations between animal and human lungs ( 29). A targeted or lung-specific treatment modality for the inhalation injury patient population is lacking ( 16, 17, 30).Īnimal models of smoke inhalation injury have been developed to assist in further understanding the pathophysiology behind smoke inhalation-associated acute lung injury. Current treatment remains supportive with a focus on improving lung oxygenation and limiting bronchial inflammation, edema, and obstruction. The complicated pathophysiology behind smoke inhalation-associated acute lung injury presents a myriad of therapeutic challenges. Smoke inhalation-associated acute lung injury worsens outcomes and contributes to a mortality level 20% higher than that seen in cutaneous burn injury alone ( 10, 16, 23). Smoke inhalation injury causes significant pulmonary injury, which increases overall mortality in the burn patient population. These animal models allow for the continued study of smoke inhalation pathophysiology to ultimately develop a better therapeutic. In summary, we successfully validated a reliable and clinically translatable survival model of lung injury and immune response in rats and mice and characterized the extent of this injury. Interestingly, rats mounted a more severe immunological response compared with mice. We confirmed that our mouse and rat models of smoke inhalation injury mimic the injury seen after human burn inhalation injury with evidence of pulmonary edema, neutrophil infiltration, and inflammatory cytokine elevation. Lung sections were hematoxylin and eosin stained, lung edema was assessed with wet-to-dry (W/D) ratio, and inflammatory cell infiltration and cytokine elevation were evaluated using flow cytometry, immunohistochemistry, and ELISA. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected for confirmatory tests. Mice and rats were anesthetized, intubated, and placed in custom-built smoke chambers to passively inhale woodchip-generated smoke. The goal of our research was threefold: 1) to develop a reproducible survival model of smoke inhalation injury in rats that closely resembled our previous mouse model, 2) to validate the rat smoke inhalation injury model using a variety of laboratory techniques, and 3) to compare and contrast our rat model with both the well-established mouse model and previously published rat models to highlight our improvements on smoke delivery and lung injury. Clinically relevant animal models are necessary for the continued investigation of the pathophysiology of inhalation injury and the development of therapeutics. Smoke inhalation injury increases morbidity and mortality.
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