Skip to main content
SpringerLink
Log in

Hypertonic Saline (NaCl 7.5 %) Reduces LPS-Induced Acute Lung Injury in Rats

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Acute respiratory distress syndrome (ARDS) is the most severe lung inflammatory manifestation and has no effective therapy nowadays. Sepsis is one of the main illnesses among ARDS causes. The use of fluid resuscitation is an important treatment for sepsis, but positive fluid balance may induce pulmonary injury. As an alternative, fluid resuscitation with hypertonic saline ((HS) NaCl 7.5 %) has been described as a promising therapeutical agent in sepsis-induced ARDS by the diminished amount of fluid necessary. Thus, we evaluated the effect of hypertonic saline in the treatment of LPS-induced ARDS. We found that hypertonic saline (NaCl 7.5 %) treatment in rat model of LPS-induced ARDS avoided pulmonary function worsening and inhibited type I collagen deposition. In addition, hypertonic saline prevented pulmonary injury by decreasing metalloproteinase 9 (MMP-9) activity in tissue. Focal adhesion kinase (FAK) activation was reduced in HS group as well as neutrophil infiltration, NOS2 expression and NO content. Our study shows that fluid resuscitation with hypertonic saline decreases the progression of LPS-induced ARDS due to inhibition of pulmonary remodeling that is observed when regular saline is used.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Del Sorbo, L., and A.S. Slutsky. 2010. Acute respiratory distress syndrome and multiple organ failure. Current Opinion in Critical Care 17: 1–6.

    Article  Google Scholar 

  2. Ranieri, V.M., G.D. Rubenfeld, B.T. Thompson, N.D. Ferguson, E. Caldwell, E. Fan, et al. 2012. Acute respiratory distress syndrome: the Berlin Definition. JAMA 307: 2526–2533.

    PubMed  Google Scholar 

  3. Marshall, R., G. Bellingan, and G. Laurent. 1998. The acute respiratory distress syndrome: fibrosis in the fast lane. Thorax 53: 815–817.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Sime, P.J., and K.M. O’Reilly. 2001. Fibrosis of the lung and other tissues: new concepts in pathogenesis and treatment. Clinical Immunology 99: 308–319.

    Article  CAS  PubMed  Google Scholar 

  5. Steinberg, J., J. Halter, H.J. Schiller, M. Dasilva, S. Landas, L.A. Gatto, et al. 2003. Metalloproteinase inhibition reduces lung injury and improves survival after cecal ligation and puncture in rats. Journal of Surgical Research 111: 185–195.

    Article  CAS  PubMed  Google Scholar 

  6. Davey, A., D.F. McAuley, and C.M. O’Kane. 2011. Matrix metalloproteinases in acute lung injury: mediators of injury and drivers of repair. European Respiratory Journal 38: 959–970.

    Article  CAS  PubMed  Google Scholar 

  7. Petroni, R.C., W.R. Teodoro, M.C. Guido, H.V. Barbeiro, F. Abatepaulo, M.C. Theobaldo, et al. 2012. Role of focal adhesion kinase in lung remodeling of endotoxemic rats. Shock 37: 524–530.

    Article  CAS  PubMed  Google Scholar 

  8. Lagares, D., O. Busnadiego, R.A. Garcia-Fernandez, M. Kapoor, S. Liu, D.E. Carter, et al. 2012. Inhibition of focal adhesion kinase prevents experimental lung fibrosis and myofibroblast formation. Arthritis and Rheumatism 64: 1653–1664.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Zeisel, M.B., V.A. Druet, J. Sibilia, J.P. Klein, V. Quesniaux, and D. Wachsmann. 2005. Cross talk between MyD88 and focal adhesion kinase pathways. Journal of Immunology 174: 7393–7397.

    Article  CAS  Google Scholar 

  10. Mu, E., R. Ding, X. An, X. Li, S. Chen, and X. Ma. 2011. Heparin attenuates lipopolysaccharide-induced acute lung injury by inhibiting nitric oxide synthase and TGF-beta/Smad signaling pathway. Thrombosis Research 129: 479–485.

    Article  PubMed  Google Scholar 

  11. Khan, R., L.A. Kirschenbaum, C. Larow, and M.E. Astiz. 2011. The effect of resuscitation fluids on neutrophil-endothelial cell interactions in septic shock. Shock 36: 440–444.

    Article  CAS  PubMed  Google Scholar 

  12. Vincent, J.L., and L. Gottin. 2011. Type of fluid in severe sepsis and septic shock. Minerva Anestesiologica 77: 1190–1196.

    PubMed  Google Scholar 

  13. Bihari, S., Prakash, S., Bersten, A.D. 2013. Post Resuscitation fluid boluses in severe sepsis or septic shock: prevalence and efficacy (Price Study). Shock.

  14. Yu, G., X. Chi, Z. Hei, N. Shen, J. Chen, W. Zhang, et al. 2012. Small volume resuscitation with 7.5% hypertonic saline, hydroxyethyl starch 130/0.4 solution and hypertonic sodium chloride hydroxyethyl starch 40 injection reduced lung injury in endotoxin shock rats: comparison with saline. Pulmonary Pharmacology & Therapeutics 25: 27–32.

    Article  Google Scholar 

  15. Velasco, I.T., V. Pontieri, M. Rocha e Silva Jr., and O.U. Lopes. 1980. Hyperosmotic NaCl and severe hemorrhagic shock. American Journal of Physiology 239: H664–H673.

    CAS  PubMed  Google Scholar 

  16. Theobaldo, M.C., F. Llimona, R.C. Petroni, E.C. Rios, I.T. Velasco, and F.G. Soriano. 2013. Hypertonic saline solution drives neutrophil from bystander organ to infectious site in polymicrobial sepsis: a cecal ligation and puncture model. PloS One 8: e74369.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Hantos, Z., B. Daroczy, B. Suki, S. Nagy, and J.J. Fredberg. 1992. Input impedance and peripheral inhomogeneity of dog lungs. Journal of Applied Physiology (1985) 72: 168–178.

    CAS  Google Scholar 

  18. Pfaffl, M.W. 2001. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Research 29, e45.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Livak, K.J., and T.D. Schmittgen. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25: 402–408.

    Article  CAS  PubMed  Google Scholar 

  20. van Haren, F.M., J. Sleigh, E.C. Boerma, M. La Pine, M. Bahr, P. Pickkers, et al. 2011. Hypertonic fluid administration in patients with septic shock: a prospective randomized controlled pilot study. Shock 37: 268–275.

    Article  Google Scholar 

  21. Angle, N., D.B. Hoyt, R. Coimbra, F. Liu, C. Herdon-Remelius, W. Loomis, et al. 1998. Hypertonic saline resuscitation diminishes lung injury by suppressing neutrophil activation after hemorrhagic shock. Shock 9: 164–170.

    Article  CAS  PubMed  Google Scholar 

  22. Staudenmayer, K.L., R.V. Maier, S. Jelacic, and E.M. Bulger. 2005. Hypertonic saline modulates innate immunity in a model of systemic inflammation. Shock 23: 459–463.

    Article  CAS  PubMed  Google Scholar 

  23. Oliveira, R.P., I. Velasco, F.G. Soriano, and G. Friedman. 2002. Clinical review: hypertonic saline resuscitation in sepsis. Critical Care 6: 418–423.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Kabir, K., J.P. Gelinas, M. Chen, D. Chen, D. Zhang, X. Luo, et al. 2002. Characterization of a murine model of endotoxin-induced acute lung injury. Shock 17: 300–303.

    Article  PubMed  Google Scholar 

  25. Yamasawa, H., Y. Ishii, and S. Kitamura. 1999. Cytokine-induced neutrophil chemoattractant in a rat model of lipopolysaccharide-induced acute lung injury. Inflammation 23: 263–274.

    CAS  PubMed  Google Scholar 

  26. Gueders, M.M., J.M. Foidart, A. Noel, and D.D. Cataldo. 2006. Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: potential implications in asthma and other lung diseases. European Journal of Pharmacology 533: 133–144.

    Article  CAS  PubMed  Google Scholar 

  27. Faffe, D.S., V.R. Seidl, P.S. Chagas, V.L. Goncalves de Moraes, V.L. Capelozzi, P.R. Rocco, et al. 2000. Respiratory effects of lipopolysaccharide-induced inflammatory lung injury in mice. European Respiratory Journal 15: 85–91.

    Article  CAS  PubMed  Google Scholar 

  28. Hagiwara, S., H. Iwasaka, S. Matsumoto, T. Noguchi, and H. Yoshioka. 2007. Coexpression of HSP47 gene and type I and type III collagen genes in LPS-induced pulmonary fibrosis in rats. Lung 185: 31–37.

    Article  CAS  PubMed  Google Scholar 

  29. Parra, E.R., W.R. Teodoro, A.P. Velosa, C.C. de Oliveira, N.H. Yoshinari, and V.L. Capelozzi. 2006. Interstitial and vascular type V collagen morphologic disorganization in usual interstitial pneumonia. Journal of Histochemistry and Cytochemistry 54: 1315–1325.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Uhlig, S., F. Brasch, L. Wollin, H. Fehrenbach, J. Richter, and A. Wendel. 1995. Functional and fine structural changes in isolated rat lungs challenged with endotoxin ex vivo and in vitro. American Journal of Pathology 146: 1235–1247.

    PubMed Central  CAS  PubMed  Google Scholar 

  31. Cely, C.M., J.T. Rojas, D.A. Maldonado, R.M. Schein, and A.A. Quartin. 2010. Use of intensive care, mechanical ventilation, both, or neither by patients with acute lung injury. Critical Care Medicine 38: 1126–1134.

    Article  PubMed  Google Scholar 

  32. Wiedemann, H.P., A.P. Wheeler, G.R. Bernard, B.T. Thompson, D. Hayden, B. deBoisblanc, et al. 2006. Comparison of two fluid-management strategies in acute lung injury. New England Journal of Medicine 354: 2564–2575.

    Article  CAS  PubMed  Google Scholar 

  33. Yuan, S.Y., Q. Shen, R.R. Rigor, and M.H. Wu. 2011. Neutrophil transmigration, focal adhesion kinase and endothelial barrier function. Microvascular Research 83: 82–88.

    Article  PubMed Central  PubMed  Google Scholar 

  34. Hsu, Y.C., L.F. Wang, and Y.W. Chien. 2007. Nitric oxide in the pathogenesis of diffuse pulmonary fibrosis. Free Radical Biology and Medicine 42: 599–607.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the FAPESP- 09/03338-7, 09/07478-8 and CNPq-470744/2004-9.

Conflict of Interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Emergency Medicine Department, Medical School, University of São Paulo, São Paulo, Brazil

    Ricardo Costa Petroni, Paolo Jose Cesare Biselli, Thais Martins de Lima, Mariana Cardillo Theobaldo, Rosângela Nascimento Pimentel, Hermes Vieira Barbeiro, Suely Ariga Kubo, Irineu Tadeu Velasco & Francisco Garcia Soriano

  2. Laboratory of Cell Biology, Department of Pathology, Medical School, University of Sao Paulo, São Paulo, Brazil

    Elia Tamaso Caldini

  3. Faculdade de Medicina da USP, LIM-51, Av. Dr. Arnaldo, 455, 3 andar, sala 3189, Cerqueira César, 01246-903, São Paulo, SP, Brazil

    Ricardo Costa Petroni

Authors
  1. Ricardo Costa Petroni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paolo Jose Cesare Biselli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thais Martins de Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mariana Cardillo Theobaldo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Elia Tamaso Caldini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rosângela Nascimento Pimentel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hermes Vieira Barbeiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Suely Ariga Kubo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Irineu Tadeu Velasco
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Francisco Garcia Soriano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ricardo Costa Petroni.

Additional information

This study was supported by the FAPESP- 09/03338-7, 09/07478-8 and CNPq-470744/2004-9.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Petroni, R.C., Biselli, P.J.C., de Lima, T.M. et al. Hypertonic Saline (NaCl 7.5 %) Reduces LPS-Induced Acute Lung Injury in Rats. Inflammation 38, 2026–2035 (2015). https://doi.org/10.1007/s10753-015-0183-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-015-0183-4

KEY WORDS

Search

Navigation