Heart Rhythm
Volume 7, Issue 12 , Pages 1835-1840 , December 2010

Biological pacemakers in canines exhibit positive chronotropic response to emotional arousal

  • Iryna N. Shlapakova, MD

      Affiliations

    • Columbia University College of Physicians and Surgeons, New York, New York
    • ,
  • Bruce D. Nearing, PhD

      Affiliations

    • Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
    • ,
  • David H. Lau, MD, PhD

      Affiliations

    • Columbia University College of Physicians and Surgeons, New York, New York
    • ,
  • Gerard J.J. Boink, MSc

      Affiliations

    • Columbia University College of Physicians and Surgeons, New York, New York
    • ,
  • Peter Danilo Jr., PhD

      Affiliations

    • Columbia University College of Physicians and Surgeons, New York, New York
    • ,
  • Yelena Kryukova, PhD

      Affiliations

    • Columbia University College of Physicians and Surgeons, New York, New York
    • ,
  • Richard B. Robinson, PhD

      Affiliations

    • Columbia University College of Physicians and Surgeons, New York, New York
    • ,
  • Ira S. Cohen, MD, PhD

      Affiliations

    • Stony Brook University Medical Center, Stony Brook, New York
    • ,
  • Michael R. Rosen, MD

      Affiliations

    • Columbia University College of Physicians and Surgeons, New York, New York
    • ,
  • Richard L. Verrier, PhD

      Affiliations

    • Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
    • Corresponding Author InformationAddress reprint requests and correspondence: Dr. Richard L. Verrier, Harvard Medical School, Beth Israel Deaconess Medical Center, Harvard-Thorndike Electrophysiology Institute, 99 Brookline Avenue, RN-301, Boston, Massachusetts 02215

Received 30 June 2009 ,Accepted 6 August 2010.

References 

  1. Plotnikov AN, Shlapakova I, Szabolcs MJ, et al. Xenografted adult human mesenchymal stem cells provide a platform for sustained biological pacemaker function in canine heart. Circulation. 2007;116:706–713
  2. Qu J, Plotnikov AN, Danilo P, et al. Expression and function of a biological pacemaker in canine heart. Circulation. 2003;107:1106–1109
  3. Verrier RL, Hagestad EL, Lown B. Delayed myocardial ischemia induced by anger. Circulation. 1987;75:249–254
  4. Tulppo MP, Makikallio TH, Takala TES, Seppanen T, Huikuri HV. Quantitative beat-to-beat analysis of heart rate dynamics during exercise. Am J Physiol. 1996;271:H244–H252
  5. Qu J, Barbuti A, Protas L, Santoro B, Cohen IS, Robinson RB. HCN2 overexpression in newborn and adult ventricular myocytes: distinct effects on gating and excitability. Circ Res. 2001;89:e8–e14
  6. Potapova I, Plotnikov A, Lu Z, et al. Human mesenchymal stem cells as a gene delivery system to create cardiac pacemakers. Circ Res. 2004;94:952–959
  7. Bucchi A, Plotnikov AN, Shlapakova I, et al. Wild-type and mutant HCN channels in a tandem biological-electronic cardiac pacemaker. Circulation. 2006;114:992–999
  8. Miake J, Marban E, Nuss HB. Gene therapy: biological pacemaker created by gene transfer. Nature. 2002;419:132–133
  9. Kehat I, Khimovich L, Caspi O, et al. Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nat Biotechnol. 2004;22:1282–1289
  10. Plotnikov AN, Sosunov EA, Qu J, et al. Biological pacemaker implanted in canine left bundle branch provides ventricular escape rhythms that have physiologically acceptable rates. Circulation. 2004;109:506–512
  11. Plotnikov AN, Bucchi A, Shlapakova I, et al. HCN212-channel biological pacemakers manifesting ventricular tachyarrhythmias are responsive to treatment with I(f) blockade. Heart Rhythm. 2008;5:282–288
  12. Tse HF, Xue T, Lau CP, et al. 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. 2006;114:1000–1011
  13. Verrier RL, Dickerson LW. Autonomic nervous system and coronary blood flow changes related to emotional activation and sleep. Circulation. 1991;83(4 Suppl):81–89II
  14. Kovach JA, Nearing BD, Verrier RL. An angerlike behavioral state potentiates myocardial ischemia-induced T-wave alternans in canines. J Am Coll Cardiol. 2001;37:1719–1725
  15. Lahiri MK, Kannankeril PJ, Goldberger JJ. Assessment of autonomic function in cardiovascular disease: physiological basis and prognostic implications. J Am Coll Cardiol. 2008;51:1725–1733
  16. Verrier RL, Tan A. Heart rate, autonomic markers, and cardiac mortality. Heart Rhythm. 2009;6:S68–S75
  17. Iellamo F, Legramante JM, Massaro M, Raimondi G, Galante A. Effects of a residential exercise training on baroreflex sensitivity and heart rate variability in patients with coronary artery disease: a randomized, controlled study. Circulation. 2000;102:2588–2592
  18. La Rovere MT, Bersano C, Gnemmi M, Specchia G, Schwartz PJ. Exercise-induced increase in baroreflex sensitivity predicts improved prognosis after myocardial infarction. Circulation. 2002;106:945–949
  19. Joung B, Tang L, Maruyama M, et al. Intracellular calcium dynamics and acceleration of sinus rhythm by beta-adrenergic stimulation. Circulation. 2009;119:788–796

 Drs. Cohen, Robinson, and Rosen have received grant funding from Boston Scientific, Inc. Gerard J.J. Boink received support from the Netherlands Heart Foundation (NHF) and the Interuniversity Cardiology Institute of the Netherlands (ICIN).

PII: S1547-5271(10)00794-0

doi: 10.1016/j.hrthm.2010.08.004

Heart Rhythm
Volume 7, Issue 12 , Pages 1835-1840 , December 2010

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