, Volume 36, Issue 5, pp 1186–1193 | Cite as

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

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


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.


venovenous extracorporeal membrane oxygenation (VV ECMO) myocardial inflammation mitochondrial function continuous renal replacement therapy (CRRT) 



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.


  1. 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.PubMedCrossRefGoogle Scholar
  2. 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.PubMedCrossRefGoogle Scholar
  3. 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.CrossRefGoogle Scholar
  4. 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.CrossRefGoogle Scholar
  5. 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.PubMedCrossRefGoogle Scholar
  6. 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.PubMedCrossRefGoogle Scholar
  7. 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.PubMedCrossRefGoogle Scholar
  8. 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.PubMedCrossRefGoogle Scholar
  9. 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.PubMedCrossRefGoogle Scholar
  10. 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.PubMedCrossRefGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. 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.CrossRefGoogle Scholar
  13. 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.PubMedCrossRefGoogle Scholar
  14. 14.
    Ventura-Clapier, R., A. Garnier, and V. Veksler. 2004. Energy metabolism in heart failure. The Journal of Physiology 555: 1–13.PubMedCrossRefGoogle Scholar
  15. 15.
    Matsuda, K., H. Hirasawa, S. Oda, H. Shiga, and K. Nakanishi. 2001. Current topics on cytokine removal technologies. Therapeutic Apheresis 5: 306–314.PubMedCrossRefGoogle Scholar
  16. 16.
    Schetz M. 1999. Non-renal indications for continuous renal replacement therapy. Kidney International. Supplement 72:S88–94.Google Scholar
  17. 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.PubMedCrossRefGoogle Scholar
  18. 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.PubMedCrossRefGoogle Scholar
  19. 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.PubMedCrossRefGoogle Scholar
  20. 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.PubMedCrossRefGoogle Scholar
  21. 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.PubMedCrossRefGoogle Scholar
  22. 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.PubMedGoogle Scholar
  23. 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.PubMedCrossRefGoogle Scholar
  24. 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.PubMedCrossRefGoogle Scholar
  25. 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.PubMedCrossRefGoogle Scholar
  26. 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.PubMedCrossRefGoogle Scholar
  27. 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.PubMedCrossRefGoogle Scholar
  28. 28.
    Galley, H.F. 2011. Oxidative stress and mitochondrial dysfunction in sepsis. British Journal of Anaesthesia 107: 57–64.PubMedCrossRefGoogle Scholar
  29. 29.
    Rudiger, A., and M. Singer. 2007. Mechanisms of sepsis-induced cardiac dysfunction. Critical Care Medicine 35: 1599–1608.PubMedCrossRefGoogle Scholar
  30. 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.PubMedCrossRefGoogle Scholar
  31. 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.PubMedCrossRefGoogle Scholar
  32. 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.PubMedCrossRefGoogle Scholar
  33. 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.PubMedCrossRefGoogle Scholar
  34. 34.
    Hirasawa, H. 2010. Indications for blood purification in critical care. Contributions to Nephrology 166: 21–30.PubMedCrossRefGoogle Scholar
  35. 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.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Juanhong Shen
    • 1
  • Wenkui Yu
    • 1
  • Qiyi Chen
    • 1
  • Jialiang Shi
    • 1
  • Yimin Hu
    • 1
  • Juanjuan Zhang
    • 1
  • Tao Gao
    • 1
  • Fengchan Xi
    • 1
  • Changsheng He
    • 1
  • Jianfeng Gong
    • 1
  • Ning Li
    • 1
  • Jieshou Li
    • 1
  1. 1.Research Institute of General Surgery, Jinling HospitalMedical School of Nanjing UniversityNanjingChina

Personalised recommendations