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A Novel Two-Hit Porcine Model of Post-Traumatic Pneumonia
Anupamaa Seshadri
1, Hyoin Kim
1, James Harbison
1, Alexandra Scheiflinger
1, David Gallo
1, Jinbong Park
2, Sidharth Shankar
1, Daniel Bent
1, James E. Kirby
1, Carl J. Hauser
1, Leo E. Otterbein
1
1Beth Israel Deaconess Medical Center, Boston, MA, 2Kyung Hee University, Seoul, Republic of Korea
Background: While it is known that trauma leads to immune dysregulation and vulnerability to infection, there is no well-established porcine model of this for mechanistic studies or translational applications. In this study, we developed a model of liver injury + hemoperitoneum and subsequent lung bacteria inoculation that appropriately recapitulates trauma-induced pneumonia resulting from a disrupted immune response after injury.
Methods: We performed a standardized liver crush (5 cm x 2.5 cm/3 kg) and hemoperitoneum (6 ml/kg) vs. sham in 30 kg Yorkshire pigs with subsequent intratracheal inoculation of bacteria (Actinobaccillus. pleuropneumoniae) to compare gross pathology, microscopic histology, bacterial counts, and serum cytokines between groups.
Results: The lungs of trauma pigs after infection demonstrated significant traumatic histologic changes as compared to uninjured infected pigs, both on the macroscopic and microscopic level. Bacterial clearance was significantly impaired after trauma (Figure), with increased infiltration of neutrophils into the lung and differential location of myeloid cells on immunostaining. IL-1ra and IL-6 were significantly increased 60 minutes after trauma.
Conclusion: We have developed a clinically relevant, novel porcine model of standardized liver crush and hemoperitoneum that results in immune dysregulation resulting in A. pleuro pneumonia that is not observed in non-trauma, infected controls. In summary, this model will allow testing of therapeutics against immune dysregulation after trauma and potential mechanisms of action.
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