Impact of intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction on left ventricular perfusion and function: a 6-month follow-up gated 99mTc-MIBI single-photon emission computed tomography study

  • Piotr Lipiec
  • Maria Krzemińska-Pakuła
  • Michał Plewka
  • Jacek Kuśmierek
  • Anna Płachcińska
  • Remigiusz Szumiński
  • Tadeusz Robak
  • Anna Korycka
  • Jarosław D. Kasprzak
Original Article

Abstract

Purpose

We investigated the impact of intracoronary injection of autologous mononuclear bone marrow cells (BMC) in patients with acute ST elevation myocardial infarction (STEMI) on left ventricular volumes, global and regional systolic function and myocardial perfusion.

Methods

The study included 39 patients with first anterior STEMI treated successfully with primary percutaneous coronary intervention. They were randomly assigned to the treatment group or the control group in a 2:1 ratio. The patients underwent baseline gated single-photon emission computed tomography (G-SPECT) 3–10 days after STEMI with quantitative and qualitative analysis of left ventricular perfusion and systolic function. On the following day, patients from the BMC treatment group were subjected to bone marrow aspiration, mononuclear BMC isolation and intracoronary injection. No placebo procedure was performed in the control group. G-SPECT was repeated 6 months after STEMI.

Results

Baseline and follow-up G-SPECT studies were available for 36 patients. At 6 months in the BMC group we observed a significantly enhanced improvement in the mean extent of the perfusion defect, the left ventricular perfusion score index, the infarct area perfusion score and the infarct area wall motion score index compared to the control group (p = 0.01–0.04). However, the changes in left ventricular volume, ejection fraction and the left ventricular wall motion score index as well as the relative changes in the infarct area wall motion score index did not differ significantly between the groups.

Conclusion

Intracoronary injection of autologous mononuclear BMC in patients with STEMI improves myocardial perfusion at 6 months. The benefit in infarct area systolic function is less pronounced and there is no apparent improvement of global left ventricular systolic function.

Keywords

Myocardial infarction Mononuclear bone marrow cells Gated single-photon emission computed tomography Left ventricular systolic function Myocardial perfusion 

Notes

Acknowledgments

The study was financially supported by a grant from the Polish Ministry of Science and Higher Education (no. 2 P05B 178 28).

Conflicts of interest

None.

References

  1. 1.
    Swedberg K, Cleland J, Dargie H, Drexler H, Follath F, Komajda M, et al.; Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur Heart J 2005;26:1115–1140.PubMedCrossRefGoogle Scholar
  2. 2.
    Abdel-Latif A, Bolli R, Tleyjeh IM, Montori VM, Perin EC, Hornung CA, et al. Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med 2007;167:989–997.PubMedCrossRefGoogle Scholar
  3. 3.
    Lipinski MJ, Biondi-Zoccai GG, Abbate A, Khianey R, Sheiban I, Bartunek J, et al. Impact of intracoronary cell therapy on left ventricular function in the setting of acute myocardial infarction: a collaborative systematic review and meta-analysis of controlled clinical trials. J Am Coll Cardiol 2007;50:1761–1767.PubMedCrossRefGoogle Scholar
  4. 4.
    Guan K, Hasenfuss G. Do stem cells in the heart truly differentiate into cardiomyocytes? J Mol Cell Cardiol 2007;43:377–387.PubMedCrossRefGoogle Scholar
  5. 5.
    Klocke FJ, Baird MG, Lorell BH, Bateman TM, Messer JV, Berman DS, et al.; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; American Society for Nuclear Cardiology. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging – executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging). Circulation 2003;108:1404–1418.PubMedCrossRefGoogle Scholar
  6. 6.
    Germano G, Kiat H, Kavanagh PB, Moriel M, Mazzanti M, Su HT, et al. Automatic quantification of ejection fraction from gated myocardial perfusion SPECT. J Nucl Med 1995;36:2138–2147.PubMedGoogle Scholar
  7. 7.
    Persson E, Carlsson M, Palmer J, Pahlm O, Arheden H. Evaluation of left ventricular volumes and ejection fraction by automated gated myocardial SPECT versus cardiovascular magnetic resonance. Clin Physiol Funct Imaging 2005;25:135–141.PubMedCrossRefGoogle Scholar
  8. 8.
    Schaefer WM, Lipke CS, Standke D, Kühl HP, Nowak B, Kaiser HJ, et al. Quantification of left ventricular volumes and ejection fraction from gated 99mTc-MIBI SPECT: MRI validation and comparison of the Emory Cardiac Tool Box with QGS and 4D-MSPECT. J Nucl Med 2005;46:1256–1263.PubMedGoogle Scholar
  9. 9.
    Adachi I, Morita K, Imran MB, Konno M, Mochizuki T, Kubo N, et al. Heterogeneity of myocardial wall motion and thickening in the left ventricle evaluated with quantitative gated SPECT. J Nucl Cardiol 2000;7:296–300.PubMedCrossRefGoogle Scholar
  10. 10.
    Korycka A, Plewka M, Krawczyńska A, Zubkowicz M, Wierzbowska A, Wrzesień-Kuś A, et al. The evaluation of efficacy of bone marrow CD34+ and CD133+ cells isolated from patients with acute myocardial infarction. Acta Haematol Pol 2008;39:73–86.Google Scholar
  11. 11.
    Plewka M, Krzemińska-Pakuła M, Jeżewski T, Wrzesień-Kuś A, Wierzbowska A, Lipiec P, et al. Early echocardiographic assessment of coronary flow reserve after intracoronary administration of bone marrow stem cells in patients with myocardial infarction. Pol J Cardiol 2008;10:48–53.Google Scholar
  12. 12.
    Matsumoto N, Berman DS, Kavanagh PB, Gerlach J, Hayes SW, Lewin HC, et al. Quantitative assessment of motion artifacts and validation of a new motion-correction program for myocardial perfusion SPECT. J Nucl Med 2001;42:687–694.PubMedGoogle Scholar
  13. 13.
    Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, Egeland T, et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med 2006;355:1199–1209.PubMedCrossRefGoogle Scholar
  14. 14.
    Janssens S, Dubois C, Bogaert J, Theunissen K, Deroose C, Desmet W, et al. Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet 2006;367:113–121.PubMedCrossRefGoogle Scholar
  15. 15.
    Strauer BE, Brehm M, Zeus T, Köstering M, Hernandez A, Sorg RV, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 2002;106:1913–1918.PubMedCrossRefGoogle Scholar
  16. 16.
    Schächinger V, Erbs S, Elsässer A, Haberbosch W, Hambrecht R, Hölschermann H, et al,; REPAIR-AMI Investigators. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 2006;355:1210–1221.PubMedCrossRefGoogle Scholar
  17. 17.
    Bartunek J, Vanderheyden M, Vandekerckhove B, Mansour S, De Bruyne B, De Bondt P, et al. Intracoronary injection of CD133-positive enriched bone marrow progenitor cells promotes cardiac recovery after recent myocardial infarction: feasibility and safety. Circulation 2005;112(9 Suppl):I178–I183.PubMedGoogle Scholar
  18. 18.
    Döbert N, Britten M, Assmus B, Berner U, Menzel C, Lehmann R, et al. Transplantation of progenitor cells after reperfused acute myocardial infarction: evaluation of perfusion and myocardial viability with FDG-PET and thallium SPECT. Eur J Nucl Med Mol Imaging 2004;31:1146–1151.PubMedCrossRefGoogle Scholar
  19. 19.
    Seeger FH, Tonn T, Krzossok N, Zeiher AM, Dimmeler S. Cell isolation procedures matter: a comparison of different isolation protocols of bone marrow mononuclear cells used for cell therapy in patients with acute myocardial infarction. Eur Heart J 2007;28:766–772.PubMedCrossRefGoogle Scholar
  20. 20.
    Yoon YS, Wecker A, Heyd L, Park JS, Tkebuchava T, Kusano K, et al. Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction. J Clin Invest 2005;115:326–338.PubMedGoogle Scholar
  21. 21.
    Kocher AA, Schuster MD, Szabolcs MJ, Takuma S, Burkhoff D, Wang J, et al. Neovascularization of ischemic myocardium by human bone marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 2001;7:430–436.PubMedCrossRefGoogle Scholar
  22. 22.
    Fazel S, Cimini M, Chen L, Li S, Angoulvant D, Fedak P, et al. Cardioprotective c-kit+ cells are from the bone marrow and regulate the myocardial balance of angiogenic cytokines. J Clin Invest 2006;116:1865–1877.PubMedCrossRefGoogle Scholar
  23. 23.
    Kinnaird T, Stabile E, Burnett MS, Lee CW, Barr S, Fuchs S, et al. Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ Res 2004;94:678–685.PubMedCrossRefGoogle Scholar
  24. 24.
    Khalil MM, Elgazzar A, Khalil W, Omar A, Ziada G. Assessment of left ventricular ejection fraction by four different methods using 99mTc tetrofosmin gated SPECT in patients with small hearts: correlation with gated blood pool. Nucl Med Commun 2005;26:885–893.PubMedCrossRefGoogle Scholar
  25. 25.
    Lipiec P, Wejner-Mik P, Krzemińska-Pakuła M, Kuśmierek J, Płachcińska A, Szumiński R, et al. Gated 99mTc-MIBI single-photon emission computed tomography for the evaluation of left ventricular ejection fraction: comparison with three-dimensional echocardiography. Ann Nucl Med 2008;22:723–726.PubMedCrossRefGoogle Scholar
  26. 26.
    Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, et al.; American Heart Association Writing Group on Myocardial Segmentation and Registration for Cardiac Imaging. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. J Nucl Cardiol 2002;9:240–245.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Piotr Lipiec
    • 1
    • 4
  • Maria Krzemińska-Pakuła
    • 1
  • Michał Plewka
    • 1
  • Jacek Kuśmierek
    • 2
  • Anna Płachcińska
    • 2
  • Remigiusz Szumiński
    • 2
  • Tadeusz Robak
    • 3
  • Anna Korycka
    • 3
  • Jarosław D. Kasprzak
    • 1
  1. 1.2nd Department of CardiologyMedical University of ŁódźŁódźPoland
  2. 2.Department of Nuclear MedicineMedical University of ŁódźŁódźPoland
  3. 3.Department of HematologyMedical University of ŁódźŁódźPoland
  4. 4.2nd Department of Cardiology, Bieganski HospitalMedical University of ŁódźŁódźPoland

Personalised recommendations