Skip to main content

Advertisement

SpringerLink
Log in

Effect of intramyocardial bone marrow-derived mononuclear cell injection on cardiac sympathetic innervation in patients with chronic myocardial ischemia

  • Original Paper
  • Published:
The International Journal of Cardiovascular Imaging Aims and scope Submit manuscript

Abstract

Intramyocardial bone marrow cell injection has been associated with improvements in myocardial perfusion and left ventricular function. The current substudy of a randomized, placebo-controlled, double-blinded study, investigated the effect of intramyocardial bone marrow cell injection on myocardial sympathetic innervation in patients with chronic myocardial ischemia. In a total of 16 patients (64 ± 8 years, 13 men), early and late iodine-123 metaiodobenzylguanidine (MIBG) imaging was performed before and 3 months after intramyocardial bone marrow cell injection. No improvements were observed in global early H/M ratio (P = 0.40), late H/M ratio (P = 0.43) and cardiac washout rate (P = 0.98). However, late 123-I MIBG SPECT defect score showed a trend to improvement in the bone marrow cell group (from 31.0 ± 7.1 to 28.1 ± 14.9) as compared to the placebo group (from 33.6 ± 8.5 to 34.5 ± 9.8, P = 0.055 between groups). This trend was mainly driven by a substantial improvement in three bone marrow cell-treated patients, which all had diabetes and severe MIBG defects. In these patients, the extent and severity of MIBG defects improved substantially independent of myocardial perfusion and cell injection sites. The present study does not demonstrate improvements in global cardiac sympathetic nerve innervation after intramyocardial bone marrow cell injection in patients with chronic myocardial ischemia. However, regional analysis of sympathetic nerve innervation reveals improvements in three diabetic patients independent of myocardial perfusion, suggestive of a therapeutic effect on diabetic cardiac sympathetic dysinnervation.

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

Similar content being viewed by others

References

  1. van Ramshorst J, Bax JJ, Beeres SL, Dibbets-Schneider P, Roes SD, Stokkel MP, de Roos A, Fibbe WE, Zwaginga JJ, Boersma E, Schalij MJ, Atsma DE (2009) Intramyocardial bone marrow cell injection for chronic myocardial ischemia: a randomized controlled trial. JAMA 301:1997–2004

    Article  PubMed  Google Scholar 

  2. Losordo DW, Henry TD, Davidson C, Sup LJ, Costa MA, Bass T, Mendelsohn F, Fortuin FD, Pepine CJ, Traverse JH, Amrani D, Ewenstein BM, Riedel N, Story K, Barker K, Povsic TJ, Harrington RA, Schatz RA (2011) Intramyocardial, autologous CD34+ cell therapy for refractory angina. Circ Res 109:428–436

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Rodrigo SF, Ramshorst J, Beeres SL, Bax JJ, Schalij MJ, Atsma DE (2011) Cell therapy for the treatment of chronic ischemic heart disease. Curr Pharm Des 17:3308–3327

    Article  CAS  PubMed  Google Scholar 

  4. Jeong JO, Kim MO, Kim H, Lee MY, Kim SW, Ii M, Lee JU, Lee J, Choi YJ, Cho HJ, Lee N, Silver M, Wecker A, Kim DW, Yoon YS (2009) Dual angiogenic and neurotrophic effects of bone marrow-derived endothelial progenitor cells on diabetic neuropathy. Circulation 119:699–708

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Shibata T, Naruse K, Kamiya H, Kozakae M, Kondo M, Yasuda Y, Nakamura N, Ota K, Tosaki T, Matsuki T, Nakashima E, Hamada Y, Oiso Y, Nakamura J (2008) Transplantation of bone marrow-derived mesenchymal stem cells improves diabetic polyneuropathy in rats. Diabetes 57:3099–3107

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Kim H, Park JS, Choi YJ, Kim MO, Huh YH, Kim SW, Han JW, Lee J, Kim S, Houge MA, Ii M, Yoon YS (2009) Bone marrow mononuclear cells have neurovascular tropism and improve diabetic neuropathy. Stem Cells 27:1686–1696

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Verberne HJ, Brewster LM, Somsen GA, van Eck-Smit BL (2008) Prognostic value of myocardial 123I-metaiodobenzylguanidine (MIBG) parameters in patients with heart failure: a systematic review. Eur Heart J 29:1147–1159

    Article  PubMed  Google Scholar 

  8. Jacobson AF, Senior R, Cerqueira MD, Wong ND, Thomas GS, Lopez VA, Agostini D, Weiland F, Chandna H, Narula J (2010) Myocardial iodine-123 meta-iodobenzylguanidine imaging and cardiac events in heart failure. Results of the prospective ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) study. J Am Coll Cardiol 55:2212–2221

    Article  PubMed  Google Scholar 

  9. Agostini D, Verberne HJ, Burchert W, Knuuti J, Povinec P, Sambuceti G, Unlu M, Estorch M, Banerjee G, Jacobson AF (2008) I-123-mIBG myocardial imaging for assessment of risk for a major cardiac event in heart failure patients: insights from a retrospective European multicenter study. Eur J Nucl Med Mol Imaging 35:535–546

    Article  PubMed  Google Scholar 

  10. Kyuma M, Nakata T, Hashimoto A, Nagao K, Sasao H, Takahashi T, Tsuchihashi K, Shimamoto K (2004) Incremental prognostic implications of brain natriuretic peptide, cardiac sympathetic nerve innervation, and noncardiac disorders in patients with heart failure. J Nucl Med 45:155–163

    CAS  PubMed  Google Scholar 

  11. Scholte AJ, Schuijf JD, Delgado V, Kok JA, Bus MT, Maan AC, Stokkel MP, Kharagitsingh AV, Dibbets-Schneider P, van der Wall EE, Bax JJ (2010) Cardiac autonomic neuropathy in patients with diabetes and no symptoms of coronary artery disease: comparison of 123I-metaiodobenzylguanidine myocardial scintigraphy and heart rate variability. Eur J Nucl Med Mol Imaging 37:1698–1705

    Article  PubMed Central  PubMed  Google Scholar 

  12. Nagamachi S, Fujita S, Nishii R, Futami S, Tamura S, Mizuta M, Nakazato M, Kurose T, Wakamatsu H (2006) Prognostic value of cardiac I-123 metaiodobenzylguanidine imaging in patients with non-insulin-dependent diabetes mellitus. J Nucl Cardiol 13:34–42

    Article  PubMed  Google Scholar 

  13. Flotats A, Carrio I, Agostini D, Le GD, Marcassa C, Schafers M, Somsen GA, Unlu M, Verberne HJ (2010) Proposal for standardization of 123I-metaiodobenzylguanidine (MIBG) cardiac sympathetic imaging by the EANM Cardiovascular Committee and the European Council of Nuclear Cardiology. Eur J Nucl Med Mol Imaging 37:1802–1812

    Article  PubMed  Google Scholar 

  14. Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, Pennell DJ, Rumberger JA, Ryan T, Verani MS (2002) 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. Circulation 105:539–542

    Article  PubMed  Google Scholar 

  15. Bax JJ, Kraft O, Buxton AE, Fjeld JG, Parizek P, Agostini D, Knuuti J, Flotats A, Arrighi J, Muxi A, Alibelli MJ, Banerjee G, Jacobson AF (2008) 123 I-mIBG scintigraphy to predict inducibility of ventricular arrhythmias on cardiac electrophysiology testing: a prospective multicenter pilot study. Circ Cardiovasc Imaging 1:131–140

    Article  PubMed  Google Scholar 

  16. Dae MW, O’Connell JW, Botvinick EH, Chin MC (1995) Acute and chronic effects of transient myocardial ischemia on sympathetic nerve activity, density, and norepinephrine content. Cardiovasc Res 30:270–280

    Article  CAS  PubMed  Google Scholar 

  17. Sasano T, Abraham MR, Chang KC, Ashikaga H, Mills KJ, Holt DP, Hilton J, Nekolla SG, Dong J, Lardo AC, Halperin H, Dannals RF, Marban E, Bengel FM (2008) Abnormal sympathetic innervation of viable myocardium and the substrate of ventricular tachycardia after myocardial infarction. J Am Coll Cardiol 51:2266–2275

    Article  PubMed  Google Scholar 

  18. Kramer CM, Nicol PD, Rogers WJ, Suzuki MM, Shaffer A, Theobald TM, Reichek N (1997) Reduced sympathetic innervation underlies adjacent noninfarcted region dysfunction during left ventricular remodeling. J Am Coll Cardiol 30:1079–1085

    Article  CAS  PubMed  Google Scholar 

  19. Schnell O, Hammer K, Muhr-Becker D, Ziegler A, Weiss M, Tatsch K, Standl E (2002) Cardiac sympathetic dysinnervation in Type 2 diabetes mellitus with and without ECG-based cardiac autonomic neuropathy. J Diabetes Complic 16:220–227

    Article  Google Scholar 

  20. Fallavollita JA, Canty JM Jr (2010) Dysinnervated but viable myocardium in ischemic heart disease. J Nucl Cardiol 17:1107–1115

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Conflicts of interest

The department of Cardiology received research grants from Medtronic, Boston Scientific, Biotronik, St. Jude Medical & GE Healthcare.

Author information

Authors and Affiliations

  1. Department of Cardiology, Leiden University Medical Centre, Post Office Box 9600, 2300 RC, Leiden, The Netherlands

    Jan van Ramshorst, Saskia L. M. A. Beeres, Sander F. Rodrigo, Arthur J. Scholte, Martin J. Schalij, Jeroen. J. Bax & Douwe E. Atsma

  2. Department of Nuclear Medicine, Leiden University Medical Centre, Leiden, The Netherlands

    Petra Dibbets-Schneider

  3. Department of Haematology, Leiden University Medical Centre, Leiden, The Netherlands

    Willem E. Fibbe & Jaap J. Zwaginga

Authors
  1. Jan van Ramshorst
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Saskia L. M. A. Beeres
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sander F. Rodrigo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Petra Dibbets-Schneider
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Arthur J. Scholte
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Willem E. Fibbe
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jaap J. Zwaginga
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Martin J. Schalij
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jeroen. J. Bax
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Douwe E. Atsma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Douwe E. Atsma.

Rights and permissions

Reprints and permissions

About this article

Cite this article

van Ramshorst, J., Beeres, S.L.M.A., Rodrigo, S.F. et al. Effect of intramyocardial bone marrow-derived mononuclear cell injection on cardiac sympathetic innervation in patients with chronic myocardial ischemia. Int J Cardiovasc Imaging 30, 583–589 (2014). https://doi.org/10.1007/s10554-014-0377-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10554-014-0377-0

Keywords

Search

Navigation