Etablierung eines posttraumatischen, murinen ALI/ARDS Modells durch Kombination von Hämorrhagischem Schock und Oleic Acid Injektion

Development of a posttraumatic, murine ALI/ARDS model by combination of hemorrhagic shock and oleic acid injection. Introduction: The Acute Respiratory Distress Syndrome (ARDS) is a life threatening complication in the treatment of severely injured patients. Up to date, treatment options of ARDS are limited and predominantly symptomatic based. The investigation of the pathophysiology of the traumatic induced, pulmonal inflammation could allow a causal ARDS therapy. Therefore, a realistic ARDS animal model is indispensable. Aim of this study is to develop a new, clinical relevant murine model of posttraumatic acute lung injury. Therefore we combine a previously established oleic acid ARDS model with a standardised, pressure-controlled haemorrhagic shock. Material and Methods: Male C57/BL6 mice were randomly assigned to groups, each consisting of six animals. In the haemorrhagic shock group blood was withdrawn and a MAD of 35±5mmHg kept for 90 minutes. In the oleic acid group 30µl OA was injected at baseline and 90 minutes thereafter. In a third group, haemorrhagic shock and oleic acid injection were combined. Animals in the sham group were narcotised and received an arterial catheter. All mice were narcotised and monitored throughout the entire observation period. All mice were sacrificed at the end of the observation period, six hours after baseline. Using ELISA assays, the serum concentration of IL-6, KC, IL-10 and MCP-1 were measured. Lungs were compared microscopically. The established Lung Injury Score was used to assess histologic lung damages. Results: In the presented model of posttraumatic ARDS, we could demonstrate a significant increase of the proinflammatoric cytokines IL-6 and KC and a strong trend of elevated MCP-1 in the group. Furthermore, in this group, the histologic lung injury score was significantly increased compared to the HS group. The Horovitz Index shows the tendency of decreasing compared to the HS group. Conclusion: The presented study shows that the combination of haemorrhagic shock and oleic acid injection leads to a reliable, standardised and clinical relevant study design which enables further studies investigating the pathology and therapeutic approaches of posttraumatic ARDS. Furthermore, this animal model fulfils the criteria for a consistent definition of ARDS in animal models postulated by Matute-Bello