Acute Lung Injury Models
Creative Animodel has been a preclinical contract research organization (CRO) for decades. We offer a full range of pre-clinical drug evaluation services and are specialized in models of acute lung injury induced by LPS, acid aspiration, hyperoxia, cecal ligation and puncture and many more. Creative Animodel offers integrated pharmaceutical services for the global scientific community and provides an exceptional client-centered experience to advance the drug discovery process.
What Is Acute Lung Injury?
Acute lung injury (ALI) and its most severe manifestation, the acute respiratory distress syndrome (ARDS), are a life-threatening condition associated with an estimated incidence of 190,000 cases and 74,500 deaths per year in the United States alone. ALI is characterized by neutrophilic inflammation of the lung and decrease of lung compliance that can result in severe pulmonary edema leading to impaired pulmonary gas exchange. Clinical ALI is associated with specific risk factors that can be broadly divided into intra-pulmonary conditions, including pneumonia and pulmonary trauma; and extra-pulmonary risk factors, including extra-pulmonary sepsis, trauma, and pancreatitis.
In the past decade, the fundamental mechanisms that initiate and propagate the lung injury have not been defined completely, although considerable advances have been made in the understanding of the pathophysiologic mechanisms, diagnostics and therapeutics of ALI. However, there are still no approved treatments that will reverse the lung destruction during ALI. The clinical focus and overall goals are to provide ventilator support while minimizing the deleterious effects of mechanical ventilation on the lung in the form of ventilator-induced lung injury. Therefore, new therapies that decrease the magnitude of lung injury and hasten lung repair are needed.
ALD Models at Creative Animodel
Animal models are of considerable value for improving our understanding the mechanisms behind the ALI and developing treatment strategies. With years of efforts, Creative Animodel has established several ALD models in an attempt to reproduce the features of human ALI in animals.
Table 1. ALD models at Creative Animodel
|Models||Systemic Features||Lung Features||Advantages|
LPS (intratracheal administration)
|Mild hypotension||• Acute: patchy intra-alveolar PMN infiltrates |
and mild changes in epithelial permeability
• Repair phase: Heals without fibrosis.
|Good model of neutrophil recruitment|
|• Acute phase: areas of necrosis, acute |
neutrophilic inflammation, hemorrhage
and intra-alveolar and interstitial edema
• Repair phase: heals with fibrosis
|Good model of epithelial barrier disruption|
|Hyperoxia||No hypotension||• Acute phase: vascular congestion, alveolar |
exudates, PMN accumulation in vessels
• Repair phase: proliferation of type 2 cells,
endothelial cells and fibroblasts, heals
with areas of scarring
|Good model of hemorrhagic injury|
|Oleic Acid (IV)||Myocardial depression, hypotension, pulmonary hypertension||• Acute phase: patchy areas of alveolar |
hemorrhage, intravascular thrombosis,
PMN infiltration and protein-rich
• Repair phase: Type II cell proliferation,
heals without fibrosis
|Good model of sepsis|
Relying on our ALI models, Creative Animodel has the capabilities to offer integrated preclinical evaluation services of pharmacology and toxicology for your drug candidates. With our state-of-art equipment such as the mechanical ventilator, our scientists can provide a functional analysis of detailed lung tissue mechanics (forced oscillations, airway hyperreactivity and pressure volume relationships), as well as traditional endpoints including gas exchange, histopathology and immuno-histochemistry. If you have any questions, please feel free to contract us.