scholarly journals Porcine model of sepsis-induced systemic inflammation and acute lung injury in donor lungs

2020 ◽  
Author(s):  
Basil Saad Nasir ◽  
Ahmed Menaouar ◽  
Caroline Landry ◽  
Jean-Francois Germain ◽  
Patrick Laplante ◽  
...  
Keyword(s):  
Animal Model ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Systemic Inflammation ◽  
Ex Vivo ◽  
Large Animal Model ◽  
Large Animal ◽  
Edema Formation ◽  
Marginal Donor ◽  
Anti Inflammatory

Abstract Background: The shortage of organ donors is a major challenge in lung transplantation. To expand the lung donor pool, ex-vivo lung perfusion (EVLP) has emerged as a platform for assessment and reconditioning marginal donor lungs. In this study a stable and reproducible large animal model of lipopolysaccharide (LPS) induced systemic inflammation and acute lung injury (ALI) was developed.Methods: Pigs (n=6) were anesthetized and monitored. After infusion of LPS (20 μg/kg) for 1 hour, followed by a 90-minute response period, lungs were procured and kept on ice for 2 hours, followed by 4 hours of EVLP. Pulmonary function, inflammatory biomarkers and edema formation were measured in vivo before procurement and during EVLP. Pro and anti-inflammatory cytokines were assayed in blood and in EVLP perfusate, which were collected before and every 30 minutes after LPS administration and EVLP.Results: LPS infusion resulted in significant hemodynamic instability, characterized by marked pulmonary hypertension, decreased systemic blood pressure and increased heart rate. This was associated with increased levels of TNFα, IL-10, IL-6, but no change in IL-1β. Ex vivo assessment of injured lungs showed graft dysfunction characterized by impaired gas exchange and edema formation. The inflammatory profile showed stable but elevated TNFα levels, and continuous production of interleukins during EVLP.Conclusion: We describe a reproducible large animal model of LPS-induced systemic inflammation and ALI. EVLP alone was unable to recondition severely injured lungs. These findings suggest that the EVLP platform requires adjuncts such as targeted anti-inflammatory agents to allow reconditioning of marginal donor lungs.

scholarly journals Cellular and acellular ex vivo lung perfusion preserve functional lung ultrastructure in a large animal model: a stereological study

2018 ◽  
Vol 19 (1) ◽  
Author(s):  
Jasmin Steinmeyer ◽  
Simon Becker ◽  
Murat Avsar ◽  
Jawad Salman ◽  
Klaus Höffler ◽  
...  
Keyword(s):  
Animal Model ◽  
Ex Vivo ◽  
Lung Perfusion ◽  
Large Animal Model ◽  
Large Animal ◽  
Ex Vivo Lung Perfusion ◽  
Lung Ultrastructure

scholarly journals The efficacy and safety of pinocembrin in a sheep model of bleomycin-induced pulmonary fibrosis

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260719
Author(s):  
Habtamu B. Derseh ◽  
Jason Q. D. Goodger ◽  
Jean-Pierre Y. Scheerlinck ◽  
Chrishan S. Samuel ◽  
Ian E. Woodrow ◽  
...  
Keyword(s):  
Animal Model ◽  
Pulmonary Fibrosis ◽  
Inflammatory Cells ◽  
Lung Parenchyma ◽  
Lung Compliance ◽  
Large Animal Model ◽  
Large Animal ◽  
Lung Pathology ◽  
Sheep Model ◽  
Anti Inflammatory

The primary flavonoid, pinocembrin, is thought to have a variety of medical uses which relate to its reported anti-oxidant, anti-inflammatory, anti-microbial and anti-cancer properties. Some studies have reported that this flavonoid has anti-fibrotic activities. In this study, we investigated whether pinocembrin would impede fibrosis, dampen inflammation and improve lung function in a large animal model of pulmonary fibrosis. Fibrosis was induced in two localized lung segments in each of the 10 sheep participating in the study. This was achieved via two infusions of bleomycin delivered bronchoscopically at a two-week interval. Another lung segment in the same sheep was left untreated, and was used as a healthy control. The animals were kept for a little over 5 weeks after the final infusion of bleomycin. Pinocembrin, isolated from Eucalyptus leaves, was administered to one of the two bleomycin damaged lung segments at a dose of 7 mg. This dose was given once-weekly over 4-weeks, starting one week after the final bleomycin infusion. Lung compliance (as a measure of stiffness) was significantly improved after four weekly administrations of pinocembrin to bleomycin-damaged lung segments. There were significantly lower numbers of neutrophils and inflammatory cells in the bronchoalveolar lavage of bleomycin-infused lung segments that were treated with pinocembrin. Compared to bleomycin damaged lung segments without drug treatment, pinocembrin administration was associated with significantly lower numbers of immuno-positive CD8+ and CD4+ T cells in the lung parenchyma. Histopathology scoring data showed that pinocembrin treatment was associated with significant improvement in inflammation and overall pathology scores. Hydroxy proline analysis showed that the administration of pinocembrin did not reduce the increased collagen content that was induced by bleomycin in this model. Analyses of Masson’s Trichrome stained sections showed that pinocembrin treatment significantly reduced the connective tissue content in lung segments exposed to bleomycin when compared to bleomycin-infused lungs that did not receive pinocembrin. The striking anti-inflammatory and modest anti-fibrotic remodelling effects of pinocembrin administration were likely linked to the compound’s ability to improve lung pathology and functional compliance in this animal model of pulmonary fibrosis.

scholarly journals A Non‐Lethal Large Animal Model of Traumatic Lung Injury (TLI)

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Emidio Sivieri ◽  
Tariq Rahman ◽  
Thomas Shaffer ◽  
Marla Wolfson
Keyword(s):  
Animal Model ◽  
Lung Injury ◽  
Large Animal Model ◽  
Large Animal

Delivery of MiRNA-92a Inhibitor Using RP1-Linked Peptide Elicits Anti-Inflammatory Effects in an Acute Lung Injury Model

2021 ◽  
Vol 17 (7) ◽  
pp. 1273-1283
Author(s):  
Chuanyu Zhuang ◽  
Chunxian Piao ◽  
Myoungjee Choi ◽  
Junkyu Ha ◽  
Minhyung Lee
Keyword(s):  
Animal Model ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Interleukin 1 ◽  
Intratracheal Instillation ◽  
Lung Epithelial Cells ◽  
Inflammatory Reactions ◽  
Tensin Homolog ◽  
Anti Inflammatory

Acute lung injury (ALI) is an inflammatory lung disease. miRNA-92a (miR92a) is induced in the lungs of ALI patients and mediates inflammatory reactions. In this study, a RP1-linked R3V6 (RP1R3V6) peptide was synthesized and evaluated as a carrier of anti-microRNA-92a oligonucleotide (AMO92a) into the lungs of an ALI animal model. In addition to the carrier function, the RP1-linked peptide can have anti-inflammatory effects in the lungs, since RP1 is an antagonist of the receptors for advanced glycation end-products (RAGEs). In a gel retardation assay, the RP1R3V6 peptide formed a spherical complex with AMO92a. In an in vitro delivery assay to L2 rat lung epithelial cells, RP1R3V6 had a lower AMO92a delivery efficiency than R3V6 and polyethyleneimine (PEI25k; 25 kDa). However, RP1R3V6 had an additional anti-inflammatory effect, reducing tumor necrosis factor-α (TNF-α) in lipopolysaccharide-activatedmacrophage cells. With the combined effects of AMO92a and RP1, the RP1R3V6/AMO92a complex reduced the miR92a level more efficiently than did the R3V6/AMO92a and PEI25k/AMO92a complexes. The RP1R3V6/AMO92a complex was administered into the lungs of ALI animals by intratracheal instillation. As a result, the expression of phosphatase and tensin homolog, a target of miR92a, was increased in the lungs. Furthermore, the RP1R3V6/AMO92a complex decreased the TNF-α and interleukin-1β (IL-1β) levels more efficiently than did the PEI25k/AMO92a and R3V6/AMO92a complexes, decreasing the damage in the lungs. These results suggest that RP1R3V6 is a useful carrier of AMO92a and has anti-inflammatory effects in an ALI animal model.

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