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Prevention and Amelioration of Rodent Ventilation-Induced Lung Injury with Either Prophylactic or Therapeutic feG Administration

  • Alison S. F. Elder
  • Andrew D. Bersten
  • Gino T. P. Saccone
  • Claudine S. Bonder
  • Dani-Louise DixonEmail author
ACUTE LUNG INJURY
  • 28 Downloads

Abstract

Purpose

Mechanical ventilation is a well-established therapy for patients with acute respiratory failure. However, up to 35% of mortality in acute respiratory distress syndrome may be attributed to ventilation-induced lung injury (VILI). We previously demonstrated the efficacy of the synthetic tripeptide feG for preventing and ameliorating acute pancreatitis-associated lung injury. However, as the mechanisms of induction of injury during mechanical ventilation may differ, we aimed to investigate the effect of feG in a rodent model of VILI, with or without secondary challenge, as a preventative treatment when administered before injury (prophylactic), or as a therapeutic treatment administered following initiation of injury (therapeutic).

Methods

Lung injury was assessed following prophylactic or therapeutic intratracheal feG administration in a rodent model of ventilation-induced lung injury, with or without secondary intratracheal lipopolysaccharide challenge.

Results

Prophylactic feG administration resulted in significant improvements in arterial blood oxygenation and respiratory mechanics, and decreased lung oedema, bronchoalveolar lavage protein concentration, histological tissue injury scores, blood vessel activation, bronchoalveolar lavage cell infiltration and lung myeloperoxidase activity in VILI, both with and without lipopolysaccharide. Therapeutic feG administration similarly ameliorated the severity of tissue damage and encouraged the resolution of injury. feG associated decreases in endothelial adhesion molecules may indicate a mechanism for these effects.

Conclusions

This study supports the potential for feG as a pharmacological agent in the prevention or treatment of lung injury associated with mechanical ventilation.

Keywords

Acute lung injury Adhesion molecules Leukocytes Mechanical ventilation Rat 

Notes

Acknowledgements

The study was funded by the Flinders Medical Centre Foundation. We thank Samantha Escarbe for technical assistance in immunohistochemical staining of lung sections.

Funding

This study was funded by the Flinders medical Centre Foundation.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted.

Supplementary material

408_2019_252_MOESM1_ESM.doc (292 kb)
Supplementary material 1 (DOC 291 kb)

References

  1. 1.
    Taniguchi LU, Caldini EG, Velasco IT, Negri EM (2010) Cytoskeleton and mechanotransduction in the pathophysiology of ventilator-induced lung injury. J Bras Pneumol 36:363–371CrossRefGoogle Scholar
  2. 2.
    Kuebler WM (2010) From a distance: ventilation-dependent extra-pulmonary injury. Transl Res 155:217–219CrossRefGoogle Scholar
  3. 3.
    Plataki M, Hubmayr RD (2010) The physical basis of ventilator-induced lung injury. Expert Rev Resp Med 4:373–385CrossRefGoogle Scholar
  4. 4.
    van Westerloo DJ, Schultz MJ, Bruno MJ, de Vos AF, Florquin S, van der Poll T (2004) Acute pancreatitis in mice impairs bacterial clearance from the lungs, whereas concurrent pneumonia prolongs the course of pancreatitis. Crit Care Med 32:1997–2001CrossRefGoogle Scholar
  5. 5.
    Kurahashi K, Kajikawa O, Sawa T, Ohara M, Gropper MA, Frank DW, Martin TR, Wiener-Kronish JP (1999) Pathogenesis of septic shock in Pseudomonas aeruginosa pneumonia. J Clin Investig 104:743–750CrossRefGoogle Scholar
  6. 6.
    Dixon DL, De Smet HR, Bersten AD (2009) Lung mechanics are both dose and tidal volume dependant in LPS-induced lung injury. Respir Physiol Neurobiol 167:333–340CrossRefGoogle Scholar
  7. 7.
    Mathison RD, Davison JS, Befus AD, Gingerich DA (2010) Salivary gland derived peptides as a new class of anti-inflammatory agents: review of preclinical pharmacology of C-terminal peptides of SMR1 protein. J Inflamm 7:49CrossRefGoogle Scholar
  8. 8.
    Elder AS, Bersten AD, Saccone GT, Dixon D-L (2013) Tripeptide feG prevents and ameliorates acute pancreatitis-associated acute lung injury in a rodent model. CHEST J 143:371–378CrossRefGoogle Scholar
  9. 9.
    Mathison RD, Christie E, Davison JS (2008) The tripeptide feG inhibits leukocyte adhesion. J Inflamm 5:6CrossRefGoogle Scholar
  10. 10.
    Rifai Y, Elder ASF, Carati CJ, Hussey DJ, Li X, Woods CM, Schloithe AC, Thomas AC, Mathison RD, Davison JS, Toouli J, Saccone GTP (2008) The tripeptide analog feG ameliorates severity of acute pancreatitis in a caerulein mouse model. Am J Physiol Gastrointest Liver Physiol 294:G1094–G1099CrossRefGoogle Scholar
  11. 11.
    Elder AS, Bersten AD, Saccone GT, Dixon DL (2013) Prevention and amelioration of rodent endotoxin-induced lung injury with administration of a novel therapeutic tripeptide feG. Pulm Pharmacol Ther 26:167–171CrossRefGoogle Scholar
  12. 12.
    Davidson KG, Bersten AD, Barr HA, Dowling KD, Nicholas TE, Doyle IR (2002) Endotoxin induces respiratory failure and increases surfactant turnover and respiration independent of alveolocapillary injury in rats. Am J Respir Crit Care Med 165:1516–1525CrossRefGoogle Scholar
  13. 13.
    Elder AS, Saccone GT, Bersten AD, Dixon DL (2011) L-Arginine-induced acute pancreatitis results in mild lung inflammation without altered respiratory mechanics. Exp Lung Res 37:1–9CrossRefGoogle Scholar
  14. 14.
    dos Santos CC, Shan Y, Akram A, Slutsky AS, Haitsma JJ (2011) Neuroimmune regulation of ventilator-induced lung injury. Am J Respir Crit Care Med 183:471–482CrossRefGoogle Scholar
  15. 15.
    Hubmayr RD (2005) Ventilator-induced lung injury without biotrauma? J Appl Physiol 99:384–385CrossRefGoogle Scholar
  16. 16.
    Network The Acute Respiratory Distress Syndrome (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. New Engl J Med 342:1–8CrossRefGoogle Scholar
  17. 17.
    Bhatia M, Moochhala S (2004) Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. J Pathol 202:145–156CrossRefGoogle Scholar
  18. 18.
    Cortjens B, De Boer OJ, De Jong R, Antonis AFG, Sabogal Piñeros YS, Lutter R, Van Woensel JBM, Bem RA (2016) Neutrophil extracellular traps cause airway obstruction during respiratory syncytial virus disease. J Pathol 238:401–411CrossRefGoogle Scholar
  19. 19.
    Muhs BE, Patel S, Yee H, Marcus S, Shamamian P (2001) Increased matrix metalloproteinase expression and activation following experimental acute pancreatitis. J Surg Res 101:21–28CrossRefGoogle Scholar
  20. 20.
    Diaz JV, Brower R, Calfee CS, Matthay MA (2010) Therapeutic strategies for severe acute lung injury. Crit Care Med 38:1644–1650CrossRefGoogle Scholar
  21. 21.
    Barisione C, Garibaldi S, Ghigliotti G, Fabbi P, Altieri P, Casale MC, Spallarossa P, Bertero G, Balbi M, Corsiglia L, Brunelli C (2010) CD14CD16 monocyte subset levels in heart failure patients. Dis Mark 28:115–124CrossRefGoogle Scholar
  22. 22.
    Hasan A (2010) Understanding mechanical ventilation: a practical handbook 2nd, edn edn. Springer, New YorkCrossRefGoogle Scholar
  23. 23.
    Del Sorbo L, Slutsky AS (2011) Acute respiratory distress syndrome and multiple organ failure. Curr Opin Crit Care 17:1–6CrossRefGoogle Scholar
  24. 24.
    Terragni PP, Rosboch G, Tealdi A, Corno E, Menaldo E, Davini O, Gandini G, Herrmann P, Mascia L, Quintel M, Slutsky AS, Gattinoni L, Ranieri VM (2007) Tidal hyperinflation during low tidal volume ventilation in acute respiratory distress syndrome. J Respir Crit Care Med 175:160–166CrossRefGoogle Scholar
  25. 25.
    Callicutt CS, Sabek O, Fukatsu K, Lundberg AH, Gaber L, Wilcox H, Kotb M, Gaber AO (2003) Diminished lung injury with vascular adhesion molecule-1 blockade in choline-deficient ethionine diet-induced pancreatitis. Surgery 133:186–196CrossRefGoogle Scholar
  26. 26.
    Privratsky JR, Tilkens SB, Newman DK, Newman PJ (2012) PECAM-1 dampens cytokine levels during LPS-induced endotoxemia by regulating leukocyte trafficking. Life Sci 90:177–184CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Critical Care Medicine, College of Medicine and Public HealthFlinders UniversityAdelaideAustralia
  2. 2.Intensive and Critical Care UnitFlinders Medical CentreAdelaideAustralia
  3. 3.Surgery, College of Medicine and Public HealthFlinders UniversityAdelaideAustralia
  4. 4.SA Pathology and the Department of Medicine, Centre for Cancer BiologyUniversity of AdelaideAdelaideAustralia

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