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Contributing factors in the development of acute lung injury in a murine double hit model

  • Philipp StörmannEmail author
  • Nils Becker
  • Leander Künnemeyer
  • Sebastian Wutzler
  • Jan Tilmann Vollrath
  • Thomas Lustenberger
  • Frank Hildebrand
  • Ingo Marzi
  • Borna Relja
Original Article
  • 26 Downloads

Abstract

Objectives

Blunt chest (thoracic) trauma (TxT) is known to contribute to the development of secondary pulmonary complications. Of these, acute lung injury (ALI) is common especially in multiply injured patients and might not only be due to the direct trauma itself, but seems to be caused by ongoing and multifactorial inflammatory changes. Nevertheless, the exact mechanisms and contributing factors of the development of ALI following blunt chest trauma are still elusive.

Methods

60 CL57BL/6N mice sustained either blunt chest trauma combined with laparotomy without further interventions or a double hit (DH) including TxT and cecal ligation puncture (CLP) after 24 h to induce ALI. Animals were killed either 6 or 24 h after the second procedure. Pulmonary expression of inflammatory mediators cxcl1, cxcl5, IL-1β and IL-6, neutrophil infiltration and lung tissue damage using the Lung Injury Score (LIS) were determined.

Results

Next to a moderate increase in other inflammatory mediators, a significant increase in CXCL1, neutrophil infiltration and lung injury was observed early after TxT, which returned to baseline levels after 24 h. DH induced significantly increased gene expression of cxcl1, cxcl5, IL-1β and IL-6 after 6 h, which was followed by the postponed significant increase in the protein expression after 24 h compared to controls. Neutrophil infiltration was significantly enhanced 24 h after DH compared to all other groups, and exerted a slight decline after 24 h. LIS has shown a significant increase after both 6 and 24 h compared to both control groups as well the late TxT group.

Conclusion

Early observed lung injury with moderate inflammatory changes after blunt chest trauma recovered quickly, and therefore, may be caused by mechanical lung injury. In contrast, lung injury in the ALI group did not undergo recovery and is closely associated with significant changes of inflammatory mediators. This model may be used for further examinations of contributing factors and therapeutic strategies to prevent ALI.

Keywords

Thoracic trauma Lung injury CLP ALI Neutrophils cxcl Cytokines 

Notes

Acknowledgements

We thank Alexander Schaible, Katrin Jurida, and Kerstin Kontradowitz for outstanding technical assistance. PS was supported by the “Frankfurter Forschungsförderung” of the Goethe University Frankfurt within the program “Nachwuchsforscher”. Grant support: The work was supported by grants from the DFG WU 820/2-1, HI 820/5-1, and RE 3304/8-1.

Compliance with ethical standards

Conflict of interest

The authors state that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Philipp Störmann
    • 1
    Email author
  • Nils Becker
    • 1
  • Leander Künnemeyer
    • 1
  • Sebastian Wutzler
    • 1
    • 2
  • Jan Tilmann Vollrath
    • 1
  • Thomas Lustenberger
    • 1
  • Frank Hildebrand
    • 3
  • Ingo Marzi
    • 1
  • Borna Relja
    • 1
  1. 1.Department of Trauma, Hand and Reconstructive SurgeryHospital of the Goethe University Frankfurt/MainFrankfurt/MainGermany
  2. 2.Department of Trauma, Hand and Orthopedic SurgeryHelios Horst Schmidt ClinicWiesbadenGermany
  3. 3.Department of Trauma SurgeryRWTH UniversityAachenGermany

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