Skip to main content
SpringerLink
Log in

Continuous Renal Replacement Therapy (CRRT) Attenuates Myocardial Inflammation and Mitochondrial Injury Induced by Venovenous Extracorporeal Membrane Oxygenation (VV ECMO) in a Healthy Piglet Model

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

In this study, we investigated the myocardial inflammation and mitochondrial function during venovenous extracorporeal membrane oxygenation (VV ECMO) and further evaluated the effects of continuous renal replacement therapy (CRRT) on them. Eighteen piglets were assigned to the control group, ECMO group, and ECMO+CRRT group. Myocardial inflammation was assessed by the activity of myeloperoxidase (MPO), myocardial concentrations, and mRNA expression of TNF-α, IL-1β, and IL-6; mitochondrial function was assessed by activities of mitochondrial complexes I–V. VV ECMO elicited a general activation of serum and myocardial inflammation and significantly decreased the activities of mitochondrial complexes I and IV. After being combined with CRRT, serum and myocardial concentrations of IL-1β and IL-6, myocardial mRNA expression of IL-6, and the activity of MPO were decreased significantly; the activities of mitochondrial complexes were increased. We conclude that myocardial inflammation was activated during ECMO therapy, inducing mitochondrial injury; moreover, CRRT reduced myocardial inflammation and partially ameliorated mitochondrial function.

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

Similar content being viewed by others

References

  1. MacLaren, G., A. Combes, and R.H. Bartlett. 2012. Contemporary extracorporeal membrane oxygenation for adult respiratory failure: life support in the new era. Intensive Care Medicine 38: 210–220.

    Article  PubMed  Google Scholar 

  2. Tiruvoipati, R., J. Botha, and G. Peek. 2012. Effectiveness of extracorporeal membrane oxygenation when conventional ventilation fails: valuable option or vague remedy? Journal of Critical Care 27: 192–198.

    Article  PubMed  Google Scholar 

  3. Peek, G.J., M. Mugford, R. Tiruvoipati, A. Wilson, E. Allen, M.M. Thalanany, et al. 2009. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. The Lancet 374: 1351–1363.

    Article  Google Scholar 

  4. Noah, M.A., G.J. Peek, S.J. Finney, M.J. Griffiths, D.A. Harrison, R. Grieve, et al. 2011. Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A(H1N1). JAMA: The Journal of the American Medical Association 306: 1659–1668.

    Article  CAS  Google Scholar 

  5. Schmid, C., A. Philipp, M. Hilker, L. Rupprecht, M. Arlt, A. Keyser, et al. 2012. Venovenous extracorporeal membrane oxygenation for acute lung failure in adults. The Journal of Heart and Lung Transplantation 31: 9–15.

    Article  PubMed  Google Scholar 

  6. Brogan, T.V., R.R. Thiagarajan, P.T. Rycus, R.H. Bartlett, and S.L. Bratton. 2009. Extracorporeal membrane oxygenation in adults with severe respiratory failure: a multi-center database. Intensive Care Medicine 35: 2105–2114.

    Article  PubMed  CAS  Google Scholar 

  7. Nehra, D., A.M. Goldstein, D.P. Doody, D.P. Ryan, Y. Chang, and P.T. Masiakos. 2009. Extracorporeal membrane oxygenation for nonneonatal acute respiratory failure: the Massachusetts General Hospital experience from 1990 to 2008. Archives of Surgery 144: 427–432.

    Article  PubMed  Google Scholar 

  8. Steinhorn, R.H., B. Isham-Schopf, C. Smith, and T.P. Green. 1989. Hemolysis during long-term extracorporeal membrane oxygenation. The Journal of Pediatrics 115: 625–630.

    Article  PubMed  CAS  Google Scholar 

  9. Kurundkar, A.R., C.R. Killingsworth, R.B. McIlwain, J.G. Timpa, Y.E. Hartman, D. He, et al. 2010. Extracorporeal membrane oxygenation causes loss of intestinal epithelial barrier in the newborn piglet. Pediatric Research 68: 128–133.

    Article  PubMed  Google Scholar 

  10. Adrian, K., K. Mellgren, M. Skogby, L.G. Friberg, G. Mellgren, and H. Wadenvik. 1998. Cytokine release during long-term extracorporeal circulation in an experimental model. Artificial Organs 22: 859–863.

    Article  PubMed  CAS  Google Scholar 

  11. Fortenberry, J.D., V. Bhardwaj, P. Niemer, J.D. Cornish, J.A. Wright, and L. Bland. 1996. Neutrophil and cytokine activation with neonatal extracorporeal membrane oxygenation. The Journal of Pediatrics 128: 670–678.

    Article  PubMed  CAS  Google Scholar 

  12. McILwain, B., T. Joseph, A.R. Kurundkar, D.W. Holt, D.R. Kelly, and Y. Hartman. 2010. Plasma concentrations of inflammatory cytokines rise rapidly during ECMO-related SIRS due to the release of pre-formed stores in the intestine. Laboratory Investigation 1: 128–139.

    Article  Google Scholar 

  13. Zanotti-Cavazzoni, S.L., and S.M. Hollenberg. 2009. Cardiac dysfunction in severe sepsis and septic shock. Current Opinion in Critical Care 15: 392–397.

    Article  PubMed  Google Scholar 

  14. Ventura-Clapier, R., A. Garnier, and V. Veksler. 2004. Energy metabolism in heart failure. The Journal of Physiology 555: 1–13.

    Article  PubMed  CAS  Google Scholar 

  15. Matsuda, K., H. Hirasawa, S. Oda, H. Shiga, and K. Nakanishi. 2001. Current topics on cytokine removal technologies. Therapeutic Apheresis 5: 306–314.

    Article  PubMed  CAS  Google Scholar 

  16. Schetz M. 1999. Non-renal indications for continuous renal replacement therapy. Kidney International. Supplement 72:S88–94.

    Google Scholar 

  17. De Vriese, A.S., R.C. Vanholder, M. Pascual, N.H. Lameire, and F.A. Colardyn. 1999. Can inflammatory cytokines be removed efficiently by continuous renal replacement therapies? Intensive Care Medicine 25: 903–910.

    Article  PubMed  Google Scholar 

  18. Skogby, M., K. Adrian, L.G. Friberg, G. Mellgren, and K. Mellgren. 2000. Influence of hemofiltration on plasma cytokine levels and platelet activation during extra corporeal membrane oxygenation. Scandinavian Cardiovascular Journal 34: 315–320.

    Article  PubMed  CAS  Google Scholar 

  19. Mu, T.S., E.G. Palmer, S.G. Batts, S.L. Lentz-Kapua, J.H. Uyehara-Lock, and C.F. Uyehara. 2012. Continuous renal replacement therapy to reduce inflammation in a piglet hemorrhage–reperfusion extracorporeal membrane oxygenation model. Pediatric Research 72: 249–255.

    Article  PubMed  CAS  Google Scholar 

  20. Naran, N., M. Sagy, and K.R. Bock. 2010. Continuous renal replacement therapy results in respiratory and hemodynamic beneficial effects in pediatric patients with severe systemic inflammatory response syndrome and multiorgan system dysfunction. Pediatric Critical Care Medicine 11: 737–740.

    Article  PubMed  Google Scholar 

  21. Ishihara, S., J.A. Ward, O. Tasaki, B.J. Pruitt, and D.W. Mozingo. 2009. Cardiac contractility during hemofiltration in an awake model of hyperdynamic endotoxemia. The Journal of Trauma 67: 1055–1061.

    Article  PubMed  Google Scholar 

  22. Li, C.M., J.H. Chen, P. Zhang, Q. He, J. Yuan, R.J. Chen, et al. 2007. Continuous veno-venous haemofiltration attenuates myocardial mitochondrial respiratory chain complexes activity in porcine septic shock. Anaesthesia and Intensive Care 35: 911–919.

    PubMed  CAS  Google Scholar 

  23. Bradford, M.M. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry 72: 248–254.

    Article  PubMed  CAS  Google Scholar 

  24. Poderoso, J.J., M.C. Carreras, C. Lisdero, N. Riobo, F. Schopfer, and A. Boveris. 1996. Nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles. Archives of Biochemistry and Biophysics 328: 85–92.

    Article  PubMed  CAS  Google Scholar 

  25. Sudheesh, N.P., T.A. Ajith, and K.K. Janardhanan. 2009. Ganoderma lucidum (Fr.) P. Karst enhances activities of heart mitochondrial enzymes and respiratory chain complexes in the aged rat. Biogerontology 10: 627–636.

    Article  PubMed  CAS  Google Scholar 

  26. Bedard, P.M., B. Zweiman, and P.C. Atkins. 1983. Quantitation by myeloperoxidase assay of neutrophil accumulation at the site of in vivo allergic reactions. Journal of Clinical Immunology 3: 84–89.

    Article  PubMed  CAS  Google Scholar 

  27. Wan, S., J.M. DeSmet, L. Barvais, M. Goldstein, J.L. Vincent, and J.L. LeClerc. 1996. Myocardium is a major source of proinflammatory cytokines in patients undergoing cardiopulmonary bypass. The Journal of Thoracic and Cardiovascular Surgery 112: 806–811.

    Article  PubMed  CAS  Google Scholar 

  28. Galley, H.F. 2011. Oxidative stress and mitochondrial dysfunction in sepsis. British Journal of Anaesthesia 107: 57–64.

    Article  PubMed  CAS  Google Scholar 

  29. Rudiger, A., and M. Singer. 2007. Mechanisms of sepsis-induced cardiac dysfunction. Critical Care Medicine 35: 1599–1608.

    Article  PubMed  Google Scholar 

  30. Zimmerman, G.A., A.H. Morris, and M. Cengiz. 1982. Cardiovascular alterations in the adult respiratory distress syndrome. The American Journal of Medicine 73: 25–34.

    Article  PubMed  CAS  Google Scholar 

  31. Bajwa, E.K., P.D. Boyce, J.L. Januzzi, M.N. Gong, B.T. Thompson, and D.C. Christiani. 2007. Biomarker evidence of myocardial cell injury is associated with mortality in acute respiratory distress syndrome. Critical Care Medicine 35: 2484–2490.

    Article  PubMed  Google Scholar 

  32. Askenazi, D.J., D.T. Selewski, M.L. Paden, D.S. Cooper, B.C. Bridges, M. Zappitelli, et al. 2012. Renal replacement therapy in critically ill patients receiving extracorporeal membrane oxygenation. Clinical Journal of the American Society of Nephrology 7: 1328–1336.

    Article  PubMed  Google Scholar 

  33. Smith, A.H., D.C. Hardison, C.R. Worden, G.M. Fleming, and M.B. Taylor. 2009. Acute renal failure during extracorporeal support in the pediatric cardiac patient. ASAIO Journal 55: 412–416.

    Article  PubMed  Google Scholar 

  34. Hirasawa, H. 2010. Indications for blood purification in critical care. Contributions to Nephrology 166: 21–30.

    Article  PubMed  Google Scholar 

  35. Honore, P.M., O. Joannes-Boyau, W. Boer, and V. Collin. 2009. High-volume hemofiltration in sepsis and SIRS: current concepts and future prospects. Blood Purification 28: 1–11.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by 12th five-year Major Program of Army Grants (no. AWS11J03; no. AWS12J001); Jiangsu Province’s Special Project of Science and Technology in Medicine (BL2012006); and Jiangsu Province’s Key Medical Talent Program (RC2011128). We thank Prof. Dehua Gong, Prof. Daxi Ji, Prof. Zhihong Liu, and other physicians, perfusionists, and nurses of Research Institute of Nephrology in Jinling Hospital for helping us perform hemofiltration.

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China

    Juanhong Shen, Wenkui Yu, Qiyi Chen, Jialiang Shi, Yimin Hu, Juanjuan Zhang, Tao Gao, Fengchan Xi, Changsheng He, Jianfeng Gong, Ning Li & Jieshou Li

Authors
  1. Juanhong Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wenkui Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qiyi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jialiang Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yimin Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Juanjuan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tao Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Fengchan Xi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Changsheng He
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jianfeng Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ning Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jieshou Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wenkui Yu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shen, J., Yu, W., Chen, Q. et al. Continuous Renal Replacement Therapy (CRRT) Attenuates Myocardial Inflammation and Mitochondrial Injury Induced by Venovenous Extracorporeal Membrane Oxygenation (VV ECMO) in a Healthy Piglet Model. Inflammation 36, 1186–1193 (2013). https://doi.org/10.1007/s10753-013-9654-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-013-9654-7

KEY WORDS

Search

Navigation