Non-Invasive Endotracheal Administration of Lipopolysaccharide to Induce Acute Lung Injury in Rodents

Acute Lung Injury (ALI) is a life-threatening inflammatory condition characterized by arterial hypoxemia, alveolar edema, compromised epithelial-endothelial capillary barrier integrity, followed by infiltration of inflammatory cells into the lung tissue, often progressing to its more severe form, Acute Respiratory Distress Syndrome (ARDS), which often culminates in acute respiratory failure. The ALI mouse models, primarily induced by lipopolysaccharide (LPS), are a key tool in research aimed at understanding the mechanisms of lung inflammation and its therapeutics. Direct and indirect rodent lung injury models offer distinct advantages as well as limitations, particularly in terms of survival rate, duration of inflammation-resolution phase, risks of surgical trauma and infection. In the present study, a non-invasive endotracheal instillation technique has been used to develop a direct ALI model in rats. This technique ensures focused delivery of LPS or test material into the lungs via the endotracheal route with the aid of a basic laryngoscope. The procedure begins with anaesthetizing the rat and positioning it in a semi-recumbent posture. Subsequently, the LPS solution is administered near the tracheal opening using a syringe attached to a rat endotracheal tube. At the time of experiment termination, lung or lavage samples are collected to assess inflammatory parameters and lung architecture. This technique outperforms other models in terms of speed, specificity, and reliability, providing specific targeting with minimal tissue damage, a low risk of mortality, and negligible off-site inflammation. This method is especially valuable in pre-clinical studies of ALI, ARDS, and related conditions like anaphylaxis or cardiac arrest. Comparatively, this method integrates more with advanced imaging techniques such as intravital microscopy to monitor drug distribution and disease progression in real time.