Skip to main content

Advertisement

SpringerLink
Log in

Regenerative therapies in electrophysiology and pacing

  • Published:
Journal of Interventional Cardiac Electrophysiology Aims and scope Submit manuscript

Abstract

The prevention and treatment of cardiac arrhythmias conferring major morbidity and mortality is far from optimal, and relies heavily on devices and drugs for the partial successes that have been seen. The greatest success has been in the use of electronic pacemakers to drive the hearts of patients having high degree heart block. Recent years have seen the beginnings of attempts to use novel approaches available through gene and cell therapies to treat both brady- and tachyarrhythmias. By far the most successful approaches to date have been seen in the development of biological pacemakers. However, the far more difficult problems posed by atrial fibrillation and ventricular tachycardia are now being addressed. In the following pages we review the approaches now in progress as well as the specific methodologic demands that must be met if these therapies are to be successful.

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
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Huikuri, H. V., Castellanos, A., & Myerburg, R. J. (2001). Sudden death due to cardiac arrhythmias. New England Journal of Medicine, 345, 1473–1482 Medline DOI 10.1056/NEJMra000650.

    Article  PubMed  CAS  Google Scholar 

  2. Huikuri, H. V., Makikallio, T. H., Raatikainen, M. J., Perkiomaki, J., Castellanos, A., & Myerburg, R. J. (2003). Prediction of sudden cardiac death: Appraisal of the studies and methods assessing the risk of sudden arrhythmic death. Circulation, 108, 110–115 Medline. DOI 10.1161/01.CIR.0000077519.18416.43.

    Article  PubMed  Google Scholar 

  3. Zipes, D. P., & Wellens, H. J. J. (1998). Sudden cardiac death. Circulation, 98, 2334–2351 Medline.

    PubMed  CAS  Google Scholar 

  4. Myerburg, R. J., Feigal, D. W. Jr, & Lindsay, B. D. (2006). Life-threatening malfunction of implantable cardiac devices. New England Journal of Medicine, 354, 2309–2311 Medline. DOI 10.1056/NEJMp068112.

    Article  PubMed  CAS  Google Scholar 

  5. Go, A. S., Hylek, E. M., Phillips, K. A., et al. (2001). Prevalence of diagnosed atrial fibrillation in adults: National implications for rhythm management and stroke prevention: The Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA, 285, 2370–2375 Medline. DOI 10.1001/jama.285.18.2370.

    Article  PubMed  CAS  Google Scholar 

  6. Miyasaka, Y., Barnes, M. E., Gersh, B. J., et al. (2006). Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation, 114, 119–125 Medline. DOI 10.1161/CIRCULATIONAHA.105.595140.

    Article  PubMed  Google Scholar 

  7. Fuster, V., Ryden, L. E., Cannom, D. S., et al. (2006). American College of Cardiology. American Heart Association Task Force on Practice Guidelines. European Society of Cardiology Committee for Practice Guidelines. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation—executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines. Journal of the American College of Cardiology, 48, 854–906 Medline. DOI 10.1016/j.jacc.2006.07.009.

    Article  PubMed  Google Scholar 

  8. Withering, W. (1979). An account of the foxglove and some of its medical uses (1785). Birmingham: Classics of Medicine Library.

    Google Scholar 

  9. Scherf, D., & Schott, A. (1973). Extrasystoles and allied arrhythmias (2nd ed.). Great Britain: Year Book Medical Publishers.

    Google Scholar 

  10. Harris, A. S., & Kokernot, R. H. (1950). Effects of diphenylhydantoin sodium (dilantin sodium) and phenobarbital sodium upon ectopic ventricular tachycardia in acute myocardial infarction. American Journal of Physiology, 163, 505–516 Medline.

    PubMed  CAS  Google Scholar 

  11. Vaughan Williams, E. M. (1979). Classification of antiarrhythmic drugs. In E. Sandoe, E. Flensted-Jensen, & K. H. Olesen (Eds.) Symposium on cardiac arrhythmias (pp. 449–472). Astra: Sodertalje.

    Google Scholar 

  12. Echt, D. S., Liebson, P. R., Mitchell, L. B., et al. (1991). Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. New England Journal of Medicine, 324, 781–788 Medline.

    Article  PubMed  CAS  Google Scholar 

  13. Waldo, A. L., Camm, A. J., deRuyter, H., et al. (1996). Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD Investigators. Survival With Oral d-Sotalol. Lancet, 348, 7–12 Medline. DOI 10.1016/S0140-6736(96)02149-6.

    Article  PubMed  CAS  Google Scholar 

  14. Spooner, P. M., & Rosen, M. R. (2000). Perspectives on arrhythmogenesis, antiarrhythmic strategies and sudden cardiac death. In P. M. Spooner, & M. R. Rosen (Eds.) Foundations of cardiac arrhythmias (pp. 1–20). New York: Marcel Dekker.

    Google Scholar 

  15. Vermes, E., Tardif, J. C., Bourassa, M. G., et al. (2003). Enalapril decreases the incidence of atrial fibrillation in patients with left ventricular dysfunction: Insight from the Studies Of Left Ventricular Dysfunction (SOLVD) trials. Circulation, 107, 2926–2931 Medline. DOI 10.1161/01.CIR.0000072793.81076.D4.

    Article  PubMed  Google Scholar 

  16. Ducharme, A., Swedberg, K., Pfeffer, M. A., et al. (2006). CHARM Investigators. Prevention of atrial fibrillation in patients with symptomatic chronic heart failure by candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program. American Heart Journal, 152, 86–92 Medline. DOI 10.1016/j.ahj.2005.06.036.

    Article  PubMed  Google Scholar 

  17. Crijns, H. J., Van den Berg, M. P., Van Gelder, I. C., & Van Veldhuisen, D. J. (1997). Management of atrial fibrillation in the setting of heart failure. European Heart Journal, 18, C45–C49 Medline.

    PubMed  CAS  Google Scholar 

  18. Pedersen, O. D., Henning, B., Køber, L., & Torp-Pedersen, C. (1999). Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction. Circulation, 100, 376–380 Medline.

    PubMed  CAS  Google Scholar 

  19. Moss, A. J., Hall, W. J., Cannom, D. S., et al. (1996). MADIT Investigators. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. New England Journal of Medicine, 335, 1933–1940 Medline. DOI 10.1056/NEJM199612263352601.

    Article  PubMed  CAS  Google Scholar 

  20. Moss, A. J., Zareba, W., Hall, W. J., Klein, H., Wilber, D. J., Cannom, D. S., et al. (2002). Multicenter Automatic Defibrillator Implantation Trial II Investigators. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. New England Journal of Medicine, 346, 877–883 Medline. DOI 10.1056/NEJMoa013474.

    Article  PubMed  Google Scholar 

  21. Bardy, G. H., Lee, K. L., Mark, D. B., et al. (2005). Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. New England Journal of Medicine, 352, 225–237 Medline. DOI 10.1056/NEJMoa043399.

    Article  PubMed  CAS  Google Scholar 

  22. Kadish, A., Dyer, A., Daubert, J. P., et al. (2004). Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) Investigators. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. New England Journal of Medicine, 350, 2151–2158 Medline. DOI 10.1056/NEJMoa033088.

    Article  PubMed  CAS  Google Scholar 

  23. Bristow, M. R., Saxon, L. A., Boehmer, J., et al. (2004). Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. New England Journal of Medicine, 350, 2140–2150 Medline. DOI 10.1056/NEJMoa032423.

    Article  PubMed  CAS  Google Scholar 

  24. Adamson, P. B., Barr, R. C., Callan, D. J., et al. (2005). The perplexing complexity of cardiac arrhythmias: Beyond electrical remodeling. Heart Rhythm, 2, 650–659 Medline. DOI 10.1016/j.hrthm.2005.03.009.

    Article  PubMed  Google Scholar 

  25. Members of the Sicilian Gambit (2001). New approaches to antiarrhythmic therapy. Emerging therapeutic applications of the cell biology of cardiac arrhythmias. European Heart Journal, 22, 2148–2163 Medline. DOI 10.1053/euhj.2001.3036.

    Article  Google Scholar 

  26. Rosen, M. (2005). Biological pacemaking: In our lifetime? Heart Rhythm, 2, 418–428 Medline. DOI 10.1016/j.hrthm.2004.12.016.

    Article  PubMed  Google Scholar 

  27. Cohen, I. S., Brink, P. R., Robinson, R. B., & Rosen, M. R. (2005). The why, what, how and when of biological pacemakers. Nature Clinical Practice Cardiovascular Medicine, 2, 374–375 Medline. DOI 10.1038/ncpcardio0276.

    Article  PubMed  Google Scholar 

  28. Edelberg, J. M., Huang, D. T., Josephson, M. E., & Rosenberg, R. D. (2001). Molecular enhancement of porcine cardiac chronotropy. Heart, 86, 559–562 Medline. DOI 10.1136/heart.86.5.559.

    Article  PubMed  CAS  Google Scholar 

  29. Miake, J., Marban, E., & Nuss, H. B. (2002). Gene therapy: Biological pacemaker created by gene transfer. Nature, 419, 132–133 Medline. DOI 10.1038/419132b.

    Article  PubMed  CAS  Google Scholar 

  30. Qu, J., Plotnikov, A. N., Danilo Jr, P., et al. (2003). Expression and function of a biological pacemaker in canine heart. Circulation, 107, 1106–1109 Medline. DOI 10.1161/01.CIR.0000059939.97249.2C.

    Article  PubMed  Google Scholar 

  31. Potapova, I., Plotnikov, A., Lu, Z., et al. (2004). Human mesenchymal stem cell as a gene delivery system to create cardiac pacemakers. Circulation Research, 94, 841–959 DOI 10.1161/01.RES.0000123827.60210.72.

    Article  CAS  Google Scholar 

  32. Bucchi, A., Plotnikov, A. N., Shlapakova, I., Danilo, P. Jr., Kryukova, Y., Qu, J., et al. (2006). Wild-type and mutant HCN channels in a tandem biological–electronic cardiac pacemaker. Circulation, 114, 992–999 Medline. DOI 10.1161/CIRCULATIONAHA.106.617613.

    Article  PubMed  Google Scholar 

  33. Tse, H. F., Xue, T., Lau, C. P., et al. (2006). Bioartificial sinus node constructed via in vivo gene transfer of an engineered pacemaker HCN Channel reduces the dependence on electronic pacemaker in a sick-sinus syndrome model. Circulation, 114, 1000–1011 Medline. DOI 10.1161/CIRCULATIONAHA.106.615385.

    Article  PubMed  CAS  Google Scholar 

  34. Kashiwakura, Y., Cho, H. C., Barth, A. S., Azene, E., & Marban, E. (2006). Gene transfer of a synthetic pacemaker channel into the heart: a novel strategy for biological pacing. Circulation, 114, 1682–1686 Medline. DOI 10.1161/CIRCULATIONAHA.106.634865.

    Article  PubMed  Google Scholar 

  35. Kehat, I., Khimovich, L., Caspi, O., et al. (2004). Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nature Biotechnology, 22, 1282–1289 Medline. DOI 10.1038/nbt1014.

    Article  PubMed  CAS  Google Scholar 

  36. Plotnikov, A. P., Shlapakova, I., Szabolcs, M. J., et al. (2007). Xenografted adult human mesenchymal stem cells provide a platform for sustained biological pacemaker function in canine heart. Circulation, 116, 706–713 Medline. DOI 10.1161/CIRCULATIONAHA.107.703231.

    Article  PubMed  Google Scholar 

  37. Sasano, T., McDonald, A. D., Kikuchi, K., & Donahue, J. K. (2006). Molecular ablation of ventricular tachycardia after myocardial infarction. Nature Medicine, 12, 1256–1258 Medline. DOI 10.1038/nm1503.

    Article  PubMed  CAS  Google Scholar 

  38. Kikuchi, K., McDonald, A. D., Sasano, T., & Donahue, J. K. (2005). Targeted modification of atrial electrophysiology by homogeneous transmural atrial gene transfer. Circulation, 111, 264–270 Medline. DOI 10.1161/01.CIR.0000153338.47507.83.

    Article  PubMed  CAS  Google Scholar 

  39. Bauer, A., McDonald, A. D., Nasir, K., et al. (2004). Inhibitory G protein overexpression provides physiologically relevant heart rate control in persistent atrial fibrillation. Circulation, 110, 3115–3120 Medline. DOI 10.1161/01.CIR.0000147185.31974.BE.

    Article  PubMed  CAS  Google Scholar 

  40. Murata, M., Cingolani, E., McDonald, A. D., Donahue, J. K., & Marban, E. (2004). Creation of a genetic calcium channel blocker by targeted gem gene transfer in the heart. Circulation Research, 95, 398–405 Medline. DOI 10.1161/01.RES.0000138449.85324.c5.

    Article  PubMed  CAS  Google Scholar 

  41. Bunch, T. J., Mahapatra, S., Bruce, G. K., et al. (2006). Impact of transforming growth factor-beta1 on atrioventricular node conduction modification by injected autologous fibroblasts in the canine heart. Circulation, 113, 2485–2494 Medline. DOI 10.1161/CIRCULATIONAHA.105.570796.

    Article  PubMed  CAS  Google Scholar 

  42. Biel, M., Schneider, A., & Wahl, C. (2002). Cardiac HCN channels: structure, function, and modulation. Trends in Cardiovascular Medicine, 12, 206–212 Medline. DOI 10.1016/S1050-1738(02)00162-7.

    Article  PubMed  CAS  Google Scholar 

  43. Plotnikov, A. N., Sosunov, E. A., Qu, J., et al. (2004). Biological pacemaker implanted in canine left bundle branch provides ventricular escape rhythms that have physiologically acceptable rates. Circulation, 109, 506–512 Medline. DOI 10.1161/01.CIR.0000114527.10764.CC.

    Article  PubMed  Google Scholar 

  44. Choi, Y. H., Stamm, C., Hammer, P. E., et al. (2006). Cardiac conduction through engineered tissue. American Journal of Pathology, 169, 72–85 Medline. DOI 10.2353/ajpath.2006.051163.

    Article  PubMed  CAS  Google Scholar 

  45. Marban, E., Nuss, H. B., & Donahue, J. K. (2002). Gene therapy for cardiac arrhythmias. Cold Spring Harbor Symposia on Quantitative Biology, 67, 527–531 Medline. DOI 10.1101/sqb.2002.67.527.

    Article  PubMed  CAS  Google Scholar 

  46. Burton, D. Y., Song, C., Fishbein, I., et al. (2003). The incorporation of an ion channel gene mutation associated with the long QT syndrome (Q9E-hMiRP1) in a plasmid vector for site-specific arrhythmia gene therapy: in vitro and in vivo feasibility studies. Human Gene Therapy, 14, 907–922 Medline. DOI 10.1089/104303403765701196.

    Article  PubMed  CAS  Google Scholar 

  47. Perlstein, I., Burton, D. Y., Ryan, K., et al. (2005). Posttranslational control of a cardiac ion channel transgene in vivo: clarithromycin–hMiRP1–Q9E interactions. Human Gene Therapy, 16, 906–910 Medline DOI 10.1089/hum.2005.16.906.

    Article  PubMed  CAS  Google Scholar 

  48. Akar, F. G., Wu, R. C., Juang, G. J., et al. (2005). Molecular mechanisms underlying K+ current downregulation in canine tachycardia-induced heart failure. American Journal of Physiology. Heart and Circulatory Physiology, 288, H2887–H2896 Medline. DOI 10.1152/ajpheart.00320.2004.

    Article  PubMed  CAS  Google Scholar 

  49. Nuss, H. B., Johns, D. C., Kaab, S., et al. (1996). Reversal of potassium channel deficiency in cells from failing hearts by adenoviral gene transfer: A prototype for gene therapy for disorders of cardiac excitability and contractility. Gene Therapy, 3, 900–912 Medline.

    PubMed  CAS  Google Scholar 

  50. Ennis, I. L., Li, R. A., Murphy, A. M., Marban, E., & Nuss, H. B. (2002). Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility. Journal of Clinical Investigation, 109, 393–400 Medline. DOI 10.1172/JCI200213359.

    PubMed  CAS  Google Scholar 

  51. Donahue, J. K., Kikuchi, K., & Sasano, T. (2005). Gene therapy for cardiac arrhythmias. Trends in Cardiovascular Medicine, 15, 219–224 Medline. DOI 10.1016/j.tcm.2005.06.007.

    Article  PubMed  CAS  Google Scholar 

  52. Neyroud, N., Nuss, H. B., Leppo, M. K., Marban, E., & Donahue, J. K. (2002). Gene delivery to cardiac muscle. Methods in Enzymology, 346, 323–334 Medline. DOI 10.1016/S0076-6879(02)46064-8.

    Article  PubMed  CAS  Google Scholar 

  53. Lehnart, S. E., & Donahue, J. K. (2003). Coronary perfusion cocktails for in vivo gene transfer. Methods in Molecular Biology, 219, 213–218 Medline.

    PubMed  CAS  Google Scholar 

  54. Roth, D. M., Lai, N. C., Gao, M. H., et al. (2004). Indirect intracoronary delivery of adenovirus encoding adenylyl cyclase increases left ventricular contractile function in mice. American Journal of Physiology. Heart and Circulatory Physiology, 287, H172–H177 Medline. DOI 10.1152/ajpheart.01009.2003.

    Article  PubMed  CAS  Google Scholar 

  55. Tomaselli, G. F., & Donahue, J. K. (2003). Somatic gene transfer and cardiac arrhythmias: Problems and prospects. Journal of Cardiovascular Electrophysiology, 14, 547–550 Medline. DOI 10.1046/j.1540-8167.2003.t01-1-02567.x.

    Article  PubMed  Google Scholar 

  56. Kornowski, R., Fuchs, S., Leon, M. B., & Epstein, S. E. (2000). Delivery strategies to achieve therapeutic myocardial angiogenesis. Circulation, 101, 454–458 Medline.

    PubMed  CAS  Google Scholar 

  57. Rosen, M. R. (2006). Are stem cells drugs? Circulation, 114, 1992–2000 Medline. DOI 10.1161/CIRCULATIONAHA.106.641670.

    Article  PubMed  Google Scholar 

  58. Zimmett, J. M., & Hare, J. M. (2005). Emerging role for bone marrow derived mesenchymal stem cells in myocardial regenerative therapy. Basic Research in Cardiology, 100, 471–481 Medline. DOI 10.1007/s00395-005-0553-4.

    Article  CAS  Google Scholar 

  59. Sekar, R. B., Kizana, E., Smith, R. R., Barth, A. S., Zhang, Y., & Marban, E. (2007). Lentiviral vector-mediated expression of GFP or Kir2.1 alters the electrophysiology of neonatal rat ventricular myocytes without inducing cytotoxicity. American Journal of Physiology. Heart and Circulatory Physiology, 293, H2757–H2770.

    Article  PubMed  CAS  Google Scholar 

  60. Jackson, K. A., Majka, S. M., Wang, H., Pocius, J., Hartley, C. J., Majesky, M. W., et al. (2001). Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. Journal of Clinical Investigation, 107(11), 1395–1402.

    Article  PubMed  CAS  Google Scholar 

  61. Kajstura, J., Rota, M., Whang, B., Cascapera, S., Hosoda, T., Bearzi, C., et al. (2005). Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion. Circulation Research, 96(1), 127–37.

    Article  PubMed  CAS  Google Scholar 

  62. Kraitchman, D. L., Heldman, A. W., Atalar, E., Amado, L. C., Martin, B. J., Pittenger, M. F., et al. (2003). In vivo magnetic resonance imaging of mesenchymal stem cells in myocardial infarction. Circulation, 107(18), 2290–2293.

    Article  PubMed  Google Scholar 

  63. Dick, A. J., Guttman, M. A., Raman, V. K., Peters, D. C., Pessanha, B. S., Hill, J. M., et al. (2003). Magnetic resonance fluoroscopy allows targeted delivery of mesenchymal stem cells to infarct borders in Swine. Circulation, 108(23), 2899–2904.

    Article  PubMed  Google Scholar 

  64. Kraitchman, D. L., Tatsumi, M., Gilson, W. D., Ishimori, T., Kedziorek, D., Walczak, P., et al. (2005). Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction. Circulation, 112(10), 1451–1461.

    Article  PubMed  Google Scholar 

  65. Barbash, I. M., Chouraqui, P., Baron, J., Feinberg, M. S., Etzion, S., Tessone, A., et al. (2003). Systemic delivery of bone marrow-derived mesenchymal stem cells to the infracted myocardium: feasibility, cell migration, and body distribution. Circulation, 108(7), 863–868.

    Article  PubMed  Google Scholar 

  66. Hofmann, M., Wollert, K. C., Meyer, G. P., Menke, A., Arseniev, L., Hertenstein, B., et al. (2005). Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation, 111(17), 2198–2202.

    Article  PubMed  Google Scholar 

  67. Laflamme, M. A., & Murry, C. E. (2005). Regenerating the heart. Nature Biotechnology, 23(7), 845–856.

    Article  PubMed  CAS  Google Scholar 

  68. Billinton, N., & Knight, A. W. (2001). Seeing the wood through the trees: a review of techniques for distinguishing green fluorescent protein from endogenous autofluorescence. Analytical Biochemistry, 291(2), 175–197.

    Article  PubMed  CAS  Google Scholar 

  69. Rosen, A. B., Kelly, D. J., Schuldt, A. J. T., Lu, J., Potapova, I. A., Doronin, S. V., et al. (2007). Finding fluorescent needles in the cardiac haystack: Tracking human mesenchymal stem cells labeled with quantum dots for quantitative in vivo 3-D fluorescence analysis. Stem Cells, 25, 2128–2138.

    Article  PubMed  CAS  Google Scholar 

  70. Ballou, B., Lagerholm, B. C., Eernst, L. A., Bruchez, M. P., & Waggoner, A. S. (2004). Noninvasive imaging of quantum dots in mice. Bioconjugate Chemistry, 75, 79–86.

    Article  CAS  Google Scholar 

  71. Valiunas, V., Doronin, S., Valiuniene, L., Potapova, I., Zuckerman, J., Walcott, B., et al. (2004). Human mesenchymal stem cells make cardiac connexins and form functional gap junctions. Journal of Physiology, 555, 617–626.

    Article  PubMed  CAS  Google Scholar 

  72. Valiunas, V., Polosina, Y. Y., Miller, H., Potapova, I. A., Valiuniene, L., Doronin, S., et al. (2005). Connexin-specific cell-to-cell transfer of short interfering RNA by gap junctions. Journal of Physiology, 568, 459–468.

    Article  PubMed  CAS  Google Scholar 

  73. Plotnikov, A. N., Bucchi, A., Shlapakova, I. N., Danilo, P. Jr., Cohen, I. S., Brink, P. R., et al. (2006). Runaway biological pacemaker function induced by HCN212 is controlled by If blockade with ivabradine. Circulation, 114, II–123.

    Google Scholar 

  74. Plotnikov, A. P., Shlapakova, I., Szabolcs, M. J., Danilo, P. Jr., Lorell, B., Potapova, I. A., et al. (2007). Xenografted adult human mesenchymal stem cells provide a platform for sustained biological pacemaker function in canine heart. Circulation, 116, 706–713.

    Article  PubMed  Google Scholar 

  75. Potapova, I., Plotnikov, A., Lu, Z., Danilo, P. Jr., Valiunas, V., Qu, J., et al. (2004). Human mesenchymal stem cell as a gene delivery system to create cardiac pacemakers. Circulation Research, 94, 841–959.

    Article  CAS  Google Scholar 

  76. Reinhard, E., Nedivi, E., Wegner, J., Skene, J. H. P., & Westerfield, M. (1994). Neural selective activation and temporal regulation of a mammalian GAP-43 promoter in zebrafish. Development, 120, 1767–1775.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The studies referred to were supported by USPHS NHLBI grants HL-28958 and HL-67101 and by Boston Scientific.

Conflict of Interest

The authors receive research support from Boston Scientific.

Author information

Authors and Affiliations

  1. Department of Pediatrics, College of Physicians and Surgeons of Columbia University, New York, NY, USA

    Michael R. Rosen

  2. Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, NY, USA

    Matthias J. Szabolcs

  3. Department of Physiology and Biophysics, Institute for Molecular Cardiology, Stony Brook University, Stony Brook, NY, USA

    Michael R. Rosen, Peter R. Brink, Ira S. Cohen & Amy B. Rosen

  4. Department of Pharmacology, Center for Molecular Therapeutics, College of Physicians and Surgeons of Columbia University, 630 West 168 Street, PH 7West-321, New York, NY, 10032, USA

    Michael R. Rosen, Ira S. Cohen, Peter Danilo Jr & Richard B. Robinson

Authors
  1. Michael R. Rosen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter R. Brink
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ira S. Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peter Danilo Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Richard B. Robinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Amy B. Rosen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Matthias J. Szabolcs
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael R. Rosen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rosen, M.R., Brink, P.R., Cohen, I.S. et al. Regenerative therapies in electrophysiology and pacing. J Interv Card Electrophysiol 22, 87–98 (2008). https://doi.org/10.1007/s10840-008-9208-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10840-008-9208-3

Keywords

Search

Navigation