Skip to main content
SpringerLink
Log in

Intracoronary delivery of mesenchymal stem cells reduces proarrhythmogenic risks in swine with myocardial infarction

  • Original Article
  • Published:
Irish Journal of Medical Science Aims and scope Submit manuscript

Abstract

Introduction

The electrophysiological consequences of mesenchymal stem cell (MSC) therapy in ischemic heart disease have not been fully understood.

Methods

Swine myocardial infarction (MI) model by intracoronary balloon occlusion received MSC solution or 0.9% NaCl. Six weeks later, heart rate turbulence (HRT), dispersion of action potential durations (APD) and repolarization time (RT) (APDd and RTd), slope of APD reconstitution curve and programmed electrical stimulation were used to evaluate the ventricular arrhythmic risks.

Results

MSC treatment could significantly ameliorate the abnormal HRT, APD90, APDd, RT and RTd. The slope of APD reconstitution curve in MSC group was higher than control group but lower than MI group. MSC therapy markedly reduced inducible malignant ventricular arrhythmias (VAs), and improved impaired cardiac performances and cardiac fibrosis.

Conclusions

This study provides strong evidence that MSC infusion via intracoronary route does not cause VAs but tends to reduce the risk of malignant VAs.

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

Similar content being viewed by others

References

  1. Janssens S, Dubois C, Bogaert J et al (2006) Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet 367:113–121

    Article  PubMed  Google Scholar 

  2. Perin EC, Dohmann HF, Borojevic R et al (2003) Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation 107:2294–2302

    Article  PubMed  Google Scholar 

  3. Menasche P, Hagege AA, Vilquin JT et al (2003) Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol 41:1078–1083

    Article  PubMed  Google Scholar 

  4. Chen HS, Kim C, Mercola M (2009) Electrophysiological challenges of cell-based myocardial repair. Circulation 120:2496–2508

    Article  PubMed  Google Scholar 

  5. Roell W, Lewalter T, Sasse P et al (2007) Engraftment of connexin 43-expressing cells prevents post-infarct arrhythmia. Nature 450:819–824

    Article  PubMed  CAS  Google Scholar 

  6. Beeres SL, Zeppenfeld K, Bax JJ et al (2007) Electrophysiological and arrhythmogenic effects of intramyocardial bone marrow cell injection in patients with chronic ischemic heart disease. Heart Rhythm 4:257–265

    Article  PubMed  Google Scholar 

  7. Hare JM, Traverse JH, Henry TD et al (2009) A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. J Am Coll Cardiol 54:2277–2286

    Article  PubMed  CAS  Google Scholar 

  8. Freyman T, Polin G, Osman H et al (2006) A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction. Eur Heart J 27:1114–1122

    Article  PubMed  Google Scholar 

  9. Pak HN, Qayyum M, Kim DT et al (2003) Mesenchymal stem cell injection induces cardiac nerve sprouting and increased tenascin expression in a Swine model of myocardial infarction. J Cardiovasc Electrophysiol 14:841–848

    Article  PubMed  Google Scholar 

  10. Price MJ, Chou CC, Frantzen M et al (2006) Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties. Int J Cardiol 111:231–239

    Article  PubMed  Google Scholar 

  11. Watanabe MA, Marine JE, Sheldon R et al (2002) Effects of ventricular premature stimulus coupling interval on blood pressure and heart rate turbulence. Circulation 106:325–330

    Article  PubMed  Google Scholar 

  12. Yuan S, Blomstrom-Lundqvist C, Pripp CM et al (1997) Signed value of monophasic action potential duration difference. A useful measure in evaluation of dispersion of repolarization in patients with ventricular arrhythmias. Eur Heart J 18:1329–1338

    PubMed  CAS  Google Scholar 

  13. Zhao ZQ, Morris CD, Budde JM et al (2003) Inhibition of myocardial apoptosis reduces infarct size and improves regional contractile dysfunction during reperfusion. Cardiovasc Res 59:132–142

    Article  PubMed  CAS  Google Scholar 

  14. Stroud JD, Baicu CF, Barnes MA et al (2002) Viscoelastic properties of pressure overload hypertrophied myocardium: effect of serine protease treatment. Am J Physiol Heart Circ Physiol 282:H2324–H2335

    PubMed  CAS  Google Scholar 

  15. Krause K, Schneider C, Lange C et al (2009) Endocardial electrogram analysis after intramyocardial injection of mesenchymal stem cells in the chronic ischemic myocardium. Pacing Clin Electrophysiol 32:1319–1328

    Article  PubMed  Google Scholar 

  16. Katritsis DG, Sotiropoulou P, Giazitzoglou E et al (2007) Electrophysiological effects of intracoronary transplantation of autologous mesenchymal and endothelial progenitor cells. Europace 9:167–171

    Article  PubMed  Google Scholar 

  17. Koller ML, Maier SK, Gelzer AR et al (2005) Altered dynamics of action potential restitution and alternans in humans with structural heart disease. Circulation 112:1542–1548

    Article  PubMed  Google Scholar 

  18. Ohara T, Ohara K, Cao JM et al (2001) Increased wave break during ventricular fibrillation in the epicardial border zone of hearts with healed myocardial infarction. Circulation 103:1465–1472

    PubMed  CAS  Google Scholar 

  19. Qu Z, Weiss JN, Garfinkel A (1999) Cardiac electrical restitution properties and stability of reentrant spiral waves: a simulation study. Am J Physiol 276:H269–H283

    PubMed  CAS  Google Scholar 

  20. Xie F, Qu Z, Garfinkel A et al (2002) Electrical refractory period restitution and spiral wave reentry in simulated cardiac tissue. Am J Physiol Heart Circ Physiol 283:H448–H460

    PubMed  CAS  Google Scholar 

  21. de Bakker JM, van Capelle FJ, Janse MJ et al (1993) Slow conduction in the infarcted human heart. ‘Zigzag’ course of activation. Circulation 88:915–926

    PubMed  Google Scholar 

  22. Maeda S, Nishizaki M, Yamawake N et al (2009) Ambulatory ECG-based T-wave alternans and heart rate turbulence predict high risk of arrhythmic events in patients with old myocardial infarction. Circ J 73:2223–2228

    Article  PubMed  Google Scholar 

  23. Pinto JM, Boyden PA (1999) Electrical remodeling in ischemia and infarction. Cardiovasc Res 42:284–297

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Natural Science of China (30800464, 30871077).

Conflict of interest

No conflict of interest exists in the submission of this manuscript.

Author information

Authors and Affiliations

  1. Department of Cardiology, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of China

    D. Wang

  2. Department of Cardiology, The First People’s Hospital of Wuxi, Wuxi, People’s Republic of China

    Y. Jin

  3. Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China

    C. Ding

  4. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300#, Nanjing, 210036, People’s Republic of China

    F. Zhang, M. Chen, B. Yang, Q. Shan, J. Zou & K. Cao

Authors
  1. D. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F. Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B. Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Q. Shan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J. Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. K. Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K. Cao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, D., Jin, Y., Ding, C. et al. Intracoronary delivery of mesenchymal stem cells reduces proarrhythmogenic risks in swine with myocardial infarction. Ir J Med Sci 180, 379–385 (2011). https://doi.org/10.1007/s11845-011-0687-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11845-011-0687-3

Keywords

Search

Navigation