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Early Increase in Myocardial Perfusion After Stem Cell Therapy in Patients Undergoing Incomplete Coronary Artery Bypass Surgery

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Abstract

Incomplete revascularization is associated with worse long-term outcomes. Autologous bone marrow cells (BMC) have recently been tested in patients with severe coronary artery disease. We tested the hypothesis that intramyocardial injection of autologous BMC increases myocardial perfusion in patients undergoing incomplete coronary artery bypass grafting (CABG). Twenty-one patients (19 men), 59 ± 7 years old, with limiting angina and multivessel coronary artery disease (CAD), not amenable to complete CABG were enrolled. BMC were obtained prior to surgery, and the lymphomonocytic fraction separated by density gradient centrifugation. During surgery, 5 mL containing 2.1 ± 1.3 × 108 BMC (CD34+ = 0.8 ± 0.3%) were injected in the ischemic non-revascularized myocardium. Myocardial perfusion was assessed by magnetic resonance imaging (MRI) at baseline and 1 month after surgery. The increase in myocardial perfusion was compared between patients with <50% (group A, n = 11) with that of patients with >50% (group B, n = 10) of target vessels (stenosis ≥ 70%) successfully bypassed. Injected myocardial segments included the inferior (n = 12), anterior (n = 7), and lateral (n = 2) walls. The number of treated vessels (2.3 ± 0.8) was significantly smaller than the number of target vessels (4.2 ± 1.0; P < 0.0001). One month after surgery, cardiac MRI showed a similar reduction (%) in the ischemic score of patients in group A (72.5 ± 3.2), compared to patients in group B (78.1 ± 3.2; P = .80). Intramyocardial injection of autologous BMC may help increase myocardial perfusion in patients undergoing incomplete CABG, even in those with fewer target vessels successfully treated. This strategy may be an adjunctive therapy for patients suffering from a more advanced (diffuse) CAD not amenable for complete direct revascularization.

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References

  1. Almeda, F. Q., & Snell, R. J. (2005). Coronary revascularization in multivessel disease. Which is better, stents or surgery? Postgraduate Medicine, 118, 11–17.

    Article  PubMed  Google Scholar 

  2. Caines, A. E., Massad, M. G., Kpodonu, J., Rebeiz, A. G., Evans, A., & Geha, A. S. (2004). Outcomes of coronary artery bypass grafting versus percutaneous coronary intervention and medical therapy for multivessel disease with and without left ventricular dysfunction. Cardiology, 101, 21–28.

    Article  PubMed  Google Scholar 

  3. Hueb, W., Soares, P. R., Gersh, B. J., et al. (2004). The medicine, angioplasty, or surgery study (MASS-II): a randomized, controlled clinical trial of three therapeutic strategies for multivessel coronary artery disease: one-year results. Journal of the American College of Cardiology, 43, 1743–1751.

    Article  PubMed  Google Scholar 

  4. Serruys, P. W., Ong, A. T., van Herwerden, L. A., et al. (2005). Five-year outcomes after coronary stenting versus bypass surgery for the treatment of multivessel disease: the final analysis of the Arterial Revascularization Therapies Study (ARTS) randomized trial. Journal of the American College of Cardiology, 46, 575–581.

    Article  PubMed  Google Scholar 

  5. Investigators, So S. (2002). Coronary artery bypass surgery versus percutaneous coronary intervention with stent implantation in patients with multivessel coronary artery disease (the Stent or Surgery trial): a randomised controlled trial. Lancet, 360, 965–970.

    Article  Google Scholar 

  6. The Bypass Angioplasty Revascularization Investigation (BARI) Investigators. (1996). Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease. The New England Journal of Medicine, 335, 217–225.

    Article  Google Scholar 

  7. Zimarino, M., Calafiore, A. M., & De Caterina, R. (2005). Complete myocardial revascularization: between myth and reality. European Heart Journal, 26, 1824–1830.

    Article  PubMed  Google Scholar 

  8. Caputo, M., Reeves, B. C., Rajkaruna, C., Awair, H., & Angelini, G. D. (2005). Incomplete revascularization during OPCAB surgery is associated with reduced mid-term event-free survival. The Annals of Thoracic Surgery, 80, 2141–2147.

    Article  PubMed  Google Scholar 

  9. McLellan, C. S., Ghali, W. A., Labinaz, M., et al. (2005). Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH) Investigators. Association between completeness of percutaneous coronary revascularization and postprocedure outcomes. American Heart Journal, 150, 800–806.

    Article  PubMed  Google Scholar 

  10. Kozower, B. D., Moon, M. R., Barner, H. B., et al. (2005). Impact of complete revascularization on long-term survival after coronary artery bypass grafting in octogenarians. The Annals of Thoracic Surgery, 80, 112–116.

    Article  PubMed  Google Scholar 

  11. Kleisli, T., Cheng, W., Jacobs, M. J., et al. (2005). In the current era, complete revascularization improves survival after coronary artery bypass surgery. The Journal of Thoracic and Cardiovascular Surgery, 129, 1283–1291.

    Article  PubMed  Google Scholar 

  12. Luttun, A., Carmeliet, G., & Carmeliet, P. (2002). Vascular progenitors: from biology to treatment. Trends in Cardiovascular Medicine, 12, 88–96.

    Article  CAS  PubMed  Google Scholar 

  13. Takahashi, T., Kalka, C., Masuda, H., et al. (1999). Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Natural Medicines, 5, 434–438.

    Article  CAS  Google Scholar 

  14. Orlic, D., Kajstura, J., Chimenti, S., et al. (2001). Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proceedings of the National Academy of Sciences of the United States of America, 98, 10344–10349.

    Article  CAS  PubMed  Google Scholar 

  15. Kocher, A. A., Schuster, M. D., Szabolcs, M. J., et al. (2001). Neovascularization of ischemic myocardium by human bone marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Natural Medicines, 7, 430–436.

    Article  CAS  Google Scholar 

  16. Orlic, D., Kajstura, J., Chimenti, S., et al. (2001). Bone marrow cells regenerate infarcted myocardium. Nature, 410, 701–705.

    Article  CAS  PubMed  Google Scholar 

  17. Assmus, B., Schachinger, V., Teupe, C., et al. (2002). Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation, 106, 3009–3017.

    Article  PubMed  Google Scholar 

  18. Wollert, K. C., Meyer, G. P., Lotz, J., et al. (2004). Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet, 364, 141–148.

    Article  PubMed  Google Scholar 

  19. Perin, E. C., Dohmann, H. F., 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 

  20. Campeau, L. (1976). Grading of angina pectoris. Circulation, 54, 522–523.

    CAS  PubMed  Google Scholar 

  21. Lunde, K., Solheim, S., Aakhus, S., et al. (2006). Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. New England Journal of Medicine, 355, 1199–1209.

    Article  CAS  PubMed  Google Scholar 

  22. Yerebakan, C., Uğurlucan, M., Kaminski, A., Westphal, B., Liebold, A., & Steinhoff, G. (2009). Autologous stem cell therapy with surgical myocardial revascularization—The Rostock University experience. Anadolu Kardiyoloji Dergisi, 9, 457–464.

    PubMed  Google Scholar 

  23. Mocini, D., Staibano, M., Mele, L., et al. (2006). Autologous bone marrow mononuclear cell transplantation in patients undergoing coronary artery bypass grafting. American Heart Journal, 151, 192–197.

    Article  PubMed  Google Scholar 

  24. Stamm, C., Westphal, B., Kleine, H. D., et al. (2003). Autologous bone marrow stem cell transplantation for myocardial regeneration. Lancet, 361, 45–46.

    Article  PubMed  Google Scholar 

  25. Zhao, Q., Sun, Y., Xia, L., Chen, A., & Wang, Z. (2008). Randomized study of mononuclear bone marrow cell transplantation in patients with coronary surgery. The Annals of Thoracic Surgery, 86, 1833–1840.

    Article  PubMed  Google Scholar 

  26. Gowdak, L. H., Schettert, I. T., Baptista, E., et al. (2008). Intramyocardial injection of autologous bone marrow cells as an adjunctive therapy to incomplete myocardial revascularization—safety issues. Clinics (Sao Paulo)., 63, 207–214.

    PubMed  Google Scholar 

  27. Schächinger, V., Erbs, S., Elsässer, A., et al. (2006). Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. New England Journal of Medicine, 355, 1199–1209.

    Article  Google Scholar 

  28. Eagle, K. A., Guyton, R. A., Davidoff, R., et al. ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary Artery Bypass Graft Surgery). American College of Cardiology website. Available at http://www.acc.org/clinical/guidelines/cabg/cabg.pdf.

  29. Gibbons RJ, RJ, Abrams J, Chatterjee K, et al. ACC/AHA 2002 guideline update for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for the Management of Patients with Chronic Stable Angina). 2002. Available at http://www.acc.org/clinical/guidelines/stable/stable.pdf.

  30. Kalkman, E. A., Bilgin, Y. M., van Haren, P., et al. (1996). Determinants of coronary reserve in rats subjected to coronary artery ligation or aortic banding. Cardiovascular Research, 32, 1088–1095.

    Article  CAS  PubMed  Google Scholar 

  31. Shintani, S., Murohara, T., Ikeda, H., et al. (2001). Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation, 103, 2776–2779.

    Article  CAS  PubMed  Google Scholar 

  32. Kalka, C., Masuda, H., Takahashi, T., et al. (2000). Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proceedings of the National Academy of Sciences of the United States of America, 97, 3422–3427.

    Article  CAS  PubMed  Google Scholar 

  33. Rafii, S., & Lyden, D. (2003). Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Natural Medicines, 9, 702–712.

    Article  CAS  Google Scholar 

  34. Li, T. S., Hamano, K., Hirata, K., Kobayashi, T., & Nishida, M. (2003). The safety and feasibility of the local implantation of autologous bone marrow cells for ischemic heart disease. Journal of Cardiac Surgery, 18(Suppl 2), S69–S75.

    Article  PubMed  Google Scholar 

  35. Carmeliet, P. (2003). Angiogenesis in health and disease. Natural Medicines, 9, 653–660.

    Article  CAS  Google Scholar 

  36. de Oliveira, S. A., Gowdak, L. H., Buckberg, G., Krieger, J. E., & The RESTORE Group. (2006). Cell biology, MRI and geometry: insight into a microscopic/macroscopic marriage. Eur J Cardiothorac Surg, 29, S259–S265.

    Article  PubMed  Google Scholar 

  37. Ang, K. L., Chin, D., Leyva, F., et al. (2008). Randomized, controlled trial of intramuscular or intracoronary injection of autologous bone marrow cells into scarred myocardium during CABG versus CABG alone. Nature Clinical Practice. Cardiovascular Medicine, 5, 663–670.

    Article  PubMed  Google Scholar 

  38. Tura, B. R., Martino, H. F., Gowdak, L. H., et al. (2007). Multicenter randomized trial of cell therapy in cardiopathies—MiHeart Study. Trials, 8, 2.

    Article  PubMed  Google Scholar 

  39. Chung, S. Y., Lee, K. Y., Chun, E. J., et al. (2010). Comparison of stress perfusion MRI and SPECT for detection of myocardial ischemia in patients with angiographically proven three-vessel coronary artery disease. AJR. American Journal of Roentgenology, 195, 356–362.

    Article  PubMed  Google Scholar 

  40. Sousa Uva, M., Cavaco, S., Oliveira, A. G., et al. (2010). Early graft patency after off-pump and on-pump coronary bypass surgery: a prospective randomized study. Eur Heart J (in press).

  41. Boeken, U., Feindt, P., Litmathe, J., & Gams, E. (2004). Comparison of complete and incomplete revascularization in CABG patients with severely impaired left ventricular function (LVF). Zeitschrift für Kardiologie, 93, 216–221.

    Article  CAS  PubMed  Google Scholar 

  42. Osswald, B. R., Tochtermann, U., Schweiger, P., Thomas, G., Vahl, C. F., & Hagl, S. (2001). Does the completeness of revascularization contribute to an improved early survival in patients up to 70 years of age? Thoracic and Cardiovascular Surgeon, 49, 373–377.

    Article  CAS  PubMed  Google Scholar 

  43. Scott, R., Blackstone, E. H., McCarthy, P. M., et al. (2000). Isolated bypass grafting of the left internal thoracic artery to the left anterior descending coronary artery: late consequences of incomplete revascularization. The Journal of Thoracic and Cardiovascular Surgery, 120, 173–184.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors would like to express their gratefulness to Teresa Cristina B. F. da Silva, RN, for her dedication to the care of patients; to Maria de Lourdes Junqueira, BS, for technical assistance; and to Meyrielli Alves Vieira, for secretarial assistance. This study was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP Grant 01/00009-0 to JEK), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq Grant 552320/2005/6 to LHWG, and 552324/2005-1 to JEK) and Fundação Zerbini.

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  1. Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, Av. Dr. Enéas de Carvalho Aguiar, 44, 05403-000, São Paulo, SP, Brazil

    Luís Henrique Wolff Gowdak, Isolmar Tadeu Schettert, Carlos Eduardo Rochitte, Luiz Augusto Ferreira Lisboa, Luís Alberto Oliveira Dallan, Luiz Antônio Machado César, Sérgio Almeida de Oliveira & José Eduardo Krieger

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  1. Luís Henrique Wolff Gowdak
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Correspondence to Luís Henrique Wolff Gowdak.

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Gowdak, L.H.W., Schettert, I.T., Rochitte, C.E. et al. Early Increase in Myocardial Perfusion After Stem Cell Therapy in Patients Undergoing Incomplete Coronary Artery Bypass Surgery. J. of Cardiovasc. Trans. Res. 4, 106–113 (2011). https://doi.org/10.1007/s12265-010-9234-2

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