scholarly journals A comparative study of a preclinical survival model of smoke inhalation injury in mice and rats

2020 ◽  
Vol 319 (3) ◽  
pp. L471-L480
Author(s):  
Alexandra I. Mercel ◽  
David C. Gillis ◽  
Kui Sun ◽  
Brooke R. Dandurand ◽  
Jenna M. Weiss ◽  
...  
Keyword(s):  
Animal Models ◽  
Lung Injury ◽  
Mouse Model ◽  
Immunological Response ◽  
Inhalation Injury ◽  
Survival Model ◽  
Smoke Inhalation ◽  
Lung Edema ◽  
Smoke Inhalation Injury ◽  
Rat Models

Smoke inhalation injury increases morbidity and mortality. Clinically relevant animal models are necessary for the continued investigation of the pathophysiology of inhalation injury and the development of therapeutics. 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. Mice and rats were anesthetized, intubated, and placed in custom-built smoke chambers to passively inhale woodchip-generated smoke. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected for confirmatory tests. 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. 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. Interestingly, rats mounted a more severe immunological response compared with mice. 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. These animal models allow for the continued study of smoke inhalation pathophysiology to ultimately develop a better therapeutic.

scholarly journals Dynamic Tracking Human Mesenchymal Stem Cells Tropism following Smoke Inhalation Injury in NOD/SCID Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
MeiJuan Song ◽  
Qi Lv ◽  
XiuWei Zhang ◽  
Juan Cao ◽  
ShuLi Sun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Inhalation Injury ◽  
Scid Mice ◽  
Alveolar Epithelial Cells ◽  
Smoke Inhalation ◽  
Control Group ◽  
Smoke Inhalation Injury

Multiple preclinical evidences have supported the potential value of mesenchymal stem cells (MSCs) for treatment of acute lung injury (ALI). However, few studies focus on the dynamic tropism of MSCs in animals with acute lung injury. In this study, we track systemically transplanted human bone marrow-derived mesenchymal stem cells (hBMSCs) in NOD/SCID mice with smoke inhalation injury (SII) through bioluminescence imaging (BLI). The results showed that hBMSCs systemically delivered into healthy NOD/SCID mouse initially reside in the lungs and then partially translocate to the abdomen after 24 h. Compared with the uninjured control group treated with hBMSCs, higher numbers of hBMSCs were found in the lungs of the SII NOD/SCID mice. In both the uninjured and SII mice, the BLI signals in the lungs steadily decreased over time and disappeared by 5 days after treatment. hBMSCs significantly attenuated lung injury, elevated the levels of KGF, decreased the levels of TNF-αin BALF, and inhibited inflammatory cell infiltration in the mice with SII. In conclusion, our findings demonstrated that more systemically infused hBMSCs localized to the lungs in mice with SII. hBMSC xenografts repaired smoke inhalation-induced lung injury in mice. This repair was maybe due to the effect of anti-inflammatory and secreting KGF of hMSCs but not associated with the differentiation of the hBMSCs into alveolar epithelial cells.

Animal models of smoke inhalation injury and related acute and chronic lung diseases

2018 ◽  
Vol 123 ◽  
pp. 107-134 ◽  
Author(s):  
Katarzyna Reczyńska ◽  
Priyanka Tharkar ◽  
Sally Yunsun Kim ◽  
Yiwei Wang ◽  
Elżbieta Pamuła ◽  
...  
Keyword(s):  
Animal Models ◽  
Lung Diseases ◽  
Inhalation Injury ◽  
Smoke Inhalation ◽  
Smoke Inhalation Injury ◽  
Chronic Lung Diseases

scholarly journals Vitamin E attenuates acute lung injury in sheep with burn and smoke inhalation injury

Redox Report ◽  
2006 ◽  
Vol 11 (2) ◽  
pp. 61-70 ◽  
Author(s):  
Naoki Morita ◽  
Katsumi Shimoda ◽  
Maret G. Traber ◽  
Martin Westphal ◽  
Perenlei Enkhbaatar ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Vitamin E ◽  
Lung Injury ◽  
Inhalation Injury ◽  
Smoke Inhalation ◽  
Smoke Inhalation Injury

Influence of Nebulized Unfractionated Heparin and N-Acetylcysteine in Acute Lung Injury After Smoke Inhalation Injury

2009 ◽  
Vol 30 (2) ◽  
pp. 249-256 ◽  
Author(s):  
Andrew C. Miller ◽  
Abel Rivero ◽  
Sophia Ziad ◽  
David J. Smith ◽  
Elamin M. Elamin
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Unfractionated Heparin ◽  
Inhalation Injury ◽  
Smoke Inhalation ◽  
Smoke Inhalation Injury

scholarly journals Beneficial pulmonary effects of a metalloporphyrinic peroxynitrite decomposition catalyst in burn and smoke inhalation injury

2011 ◽  
Vol 300 (2) ◽  
pp. L167-L175 ◽  
Author(s):  
Matthias Lange ◽  
Csaba Szabo ◽  
Perenlei Enkhbaatar ◽  
Rhykka Connelly ◽  
Eszter Horvath ◽  
...  
Keyword(s):  
Lung Injury ◽  
Total Body Surface Area ◽  
Weight Ratio ◽  
Dry Weight ◽  
Inhalation Injury ◽  
Smoke Inhalation ◽  
Control Group ◽  
Significant Drop ◽  
Cytotoxic Effects ◽  
Smoke Inhalation Injury

During acute lung injury, nitric oxide (NO) exerts cytotoxic effects by reacting with superoxide radicals, yielding the reactive nitrogen species peroxynitrite (ONOO−). ONOO− exerts cytotoxic effects, among others, by nitrating/nitrosating proteins and lipids, by activating the nuclear repair enzyme poly(ADP-ribose) polymerase and inducing VEGF. Here we tested the effect of the ONOO− decomposition catalyst INO-4885 on the development of lung injury in chronically instrumented sheep with combined burn and smoke inhalation injury. The animals were randomized to a sham-injured group ( n = 7), an injured control group [48 breaths of cotton smoke, 3rd-degree burn of 40% total body surface area ( n = 7)], or an injured group treated with INO-4885 ( n = 6). All sheep were mechanically ventilated and fluid-resuscitated according to the Parkland formula. The injury-related increases in the abundance of 3-nitrotyrosine, a marker of protein nitration by ONOO−, were prevented by INO-4885, providing evidence for the neutralization of ONOO− action by the compound. Burn and smoke injury induced a significant drop in arterial Po2-to-inspired O2 fraction ratio and significant increases in pulmonary shunt fraction, lung lymph flow, lung wet-to-dry weight ratio, and ventilatory pressures; all these changes were significantly attenuated by INO-4885 treatment. In addition, the increases in IL-8, VEGF, and poly(ADP-ribose) in lung tissue were significantly attenuated by the ONOO− decomposition catalyst. In conclusion, the current study suggests that ONOO− plays a crucial role in the pathogenesis of pulmonary microvascular hyperpermeability and pulmonary dysfunction following burn and smoke inhalation injury in sheep. Administration of an ONOO− decomposition catalyst may represent a potential treatment option for this injury.

scholarly journals Molecular biological effects of selective neuronal nitric oxide synthase inhibition in ovine lung injury

2010 ◽  
Vol 298 (3) ◽  
pp. L427-L436 ◽  
Author(s):  
Fiona D. Saunders ◽  
Martin Westphal ◽  
Perenlei Enkhbaatar ◽  
Jianpu Wang ◽  
Konrad Pazdrak ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Lung Injury ◽  
Lung Tissue ◽  
Neuronal Nitric Oxide Synthase ◽  
Inhalation Injury ◽  
Smoke Inhalation ◽  
Smoke Inhalation Injury ◽  
Pulmonary Shunting ◽  
Oxide Synthase

Neuronal nitric oxide synthase is critically involved in the pathogenesis of acute lung injury resulting from combined burn and smoke inhalation injury. We hypothesized that 7-nitroindazole, a selective neuronal nitric oxide synthase inhibitor, blocks central molecular mechanisms involved in the pathophysiology of this double-hit insult. Twenty-five adult ewes were surgically prepared and randomly allocated to 1) an uninjured, untreated sham group ( n = 7), 2) an injured control group with no treatment ( n = 7), 3) an injury group treated with 7-nitroindazole from 1-h postinjury to the remainder of the 24-h study period ( n = 7), or 4) a sham-operated group subjected only to 7-nitroindazole to judge the effects in health. The combination injury was associated with twofold increased activity of neuronal nitric oxide synthase and oxidative/nitrosative stress, as indicated by significant increases in plasma nitrate/nitrite concentrations, 3-nitrotyrosine (an indicator of peroxynitrite formation), and malondialdehyde lung tissue content. The presence of systemic inflammation was evidenced by twofold, sixfold, and threefold increases in poly(ADP-ribose) polymerase, IL-8, and myeloperoxidase lung tissue concentrations, respectively (each P < 0.05 vs. sham). These molecular changes were linked to tissue damage, airway obstruction, and pulmonary shunting with deteriorated gas exchange. 7-Nitroindazole blocked, or at least attenuated, all these pathological changes. Our findings suggest 1) that nitric oxide formation derived from increased neuronal nitric oxide synthase activity represents a pivotal reactive agent in the patho-physiology of combined burn and smoke inhalation injury and 2) that selective neuronal nitric oxide synthase inhibition represents a goal-directed approach to attenuate the degree of injury.

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