Basic Research in Cardiology

, Volume 75, Issue 6, pp 772–779 | Cite as

Catechnolamine-cyclic-AMP-Ca2+-induced ventricular tachycardia in the intact pig heart

  • T. Podzuweit
Original Contributions


Agents known to increase cAMP levels in the myocardium were infused subepicaridally (focal infusion, 10 μl/min) in open-chested pigs. Infusion of noradrenalin (NA), adrenalin (10−5M each) or isoproterenol (10−6M) in the presence of Ca2+ (2.5·10−3M) consistently produced ventricular tachycardia (VT) within 60s. This tachycardia could be mimicked by electrical stimulation of the infusion area. The NA/CA2+-VT could be maintained for 30 min and was readily reversible after stopping the infusion. Infusion of N6, O2-dibutyryl-cAMP or N6-monobutyryl-cAMP (5·10−2M each) produced long-lasting VT within 10–20 min. VT was also induced by infusion of 8-Br-cAMP (5·10−2M) together with the phosphodiesterase inhibitor Ro Na/Ca2+-VT was abolished by calcium antagonists [isoptin, D 600 (10−4M each), MnCl2 (5 · 10−4M)] and beta-adrenoceptor blocking agents [propranolol (10−4M each), pindolol (10−6)], but was not suppressed by tetrodotoxin (up to 10−5M). Infusion of 5 · 10−2M N6-monobutyryl-2'-deoxy-cAMP,. 2.5 · 10−3M CaCl2/0.9% NaCl or 10−1M Na-butyrate did not precipitate VT. Tissue analysis showed that myocardial cAMP was increased at the infusion site when the NA/Ca2+-VT ensued. It is concluded that the catecholamine-cAMP-Ca2+ system may play an important role in the initiation and perpetuation of VT, possibly by producing automaticity in ventricular fibres via slow Ca2+ channels.


Propranolol Isoptin Ventricular Tachycardia Phosphodiesterase Isoproterenol 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Katecholamin-zyklisches AMP-Ca2+ versursacht ventrikuläre Tachykardien am intakten Schweineherzen


Substanzen, die den cAMP-Gehalt des Gewebes erhöhen, wurden subepikardial in das schlagende Schweineherz infundiert (10 μl/min). Durch Infusion von Noradrenalin (NA), Adrenalin (je 10−5M) oder Isoproterenol (10−6M) zusammen mit Ca2+ (2,5 · 10−3M) wurde innerhalb von 60 s ventrikuläre Tachykardie (VT) ausgelöst. Diese Tachykardie konnte durch Elektrostimulation des Infusionsgebietes simuliert werden. Die NA/Ca2+-VT konnte wiederholt hervorgerufen werden und ließ sich für 30 min aufrechterhalten. Infusion von N6-monobutyryl-cAMP oder N6, O2-dibutyryl-cAMP (je 5 · 10−2M) verursachte nach 10–20 min lang anhaltende VT. VT wurde auch durch gemeinsame Infusion von 8-Br-cAMP (5 · 10−2M) und Phosphodiesteraseinhibitor Ro 7-2956 (5 · 10−4M) verursacht, während die Infusion der einzelnen Substanzen wirkungslos war. Die NA/Ca2+-VT wurde durch Kalziumantagonisten [Isoptin, D 600 (10−4M), MnCl2 (5 · 10−4M)] und Betarezeptorenblocker [Progranolol (10−4M)], jedoch nicht durch Tetrodotoxin (bis 10−5M) beendet. Die Infusion von 5 · 10−2M N6-monobutyryl-2′-deoxy-cAMP, 2,5 · 10−3M CaCl2/0,9% NaCl oder 10−1M Natriumbutyrat rief keine VT hervor. Die Gewebsanalyse ergab, daß der cAMP-Gehalt im Infusionsgebiet erhöht war, als die Na/Ca2+-VT begann. Die Ergebnisse zeigen, daß durch regionale Überaktivierung des Katecholamin-cAMP-Ca2+-Systems VT hervorgerufen werden kann. Als möglicher Wirkungsmecanismus wird durch Verstärkung des langsamen Ca2+-Einstromes in Ventrikelzellen entstehende Automatie angenommen.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Cranefield, P. F.: The Conduction of the Cardiac Impulse. The Slow Response and Cardiac Arrhythmias (Futura Publishing Company, Mount Kisco, New York, 1975).Google Scholar
  2. 2.
    Drummond, G. I., S. J. Hemmings: Inotropic and chronotropic effects of dibutyryl cyclic AMP. Advances in Cyclic Nucleotide Research1, 307–316 (1972).PubMedGoogle Scholar
  3. 3.
    Goshima, K.: Intiation of beating in quiescent myocardial cells by norepinephrine, by contact with beating cells and by electrical stimulation of adjacent FL cells. Expl. Cell Res.84, 223–234 (1974).CrossRefGoogle Scholar
  4. 4.
    Goshima, K.: Antagonistic influences of dibutyryl cyclic AMP and dibutyryl cyclic GMP on the beating rate of cultured mouse myocardial cells. J. Molec. cell. Cardiol.8, 713–725 (1976).CrossRefGoogle Scholar
  5. 5.
    Katz, A. M.: Physiology of the Heart, pp. 328–330, Raven Press, (New York 1977).Google Scholar
  6. 6.
    Kohlhardt, M., B. Bauer, H. Krause, A. Fleckenstein: Differentiation of the transmembrane Na and Ca channels in mammalian cardiac fibres by the use of specific inhibitors. Pflügers Arch.335, 309–322 (1972).CrossRefGoogle Scholar
  7. 7.
    Krause, E.-G., W. Halle, E. Kallabis, A. Wolenberger: Positive chronotripic response of cultured isolated rat heart cells to N6,2′-O-dibutyryl-3′-5′-adenosine monophosphate. J. molec. cell. Cardiol.1, 1–10 (1970).CrossRefGoogle Scholar
  8. 8.
    Otsuka, M.: Die Wirkung von Andrenalin auf Purkinje-Fasern von Säugetierherzen. Pflügers Arch.266, 512–517 (1958).CrossRefGoogle Scholar
  9. 9.
    Reuter, H.: Localization of beta adrenergic receptors, and effects of norradrenaline and cyclic nucleotides on action potentials, ionic icurrents and tension in mammalian cardiac muscle. J. Physiol., Lond.242, 429–451 (1974).Google Scholar
  10. 10.
    Tritthard, H.: The comparison of cAMP and β-adrenergic effects on Ca-mediated action potentials of cat ventricular myocardium. Naunyn-Schmiedeberg's Arch. Pharmacol.284, R 85 (1974).Google Scholar
  11. 11.
    Tsien, R. W.: Adrenaline-like effects of intracellular iontophoresis of cyclic AMP in cardiac Purkinje fibres. Nature new Biol.245, 120–122 (1973).PubMedGoogle Scholar
  12. 12.
    Tsien, R. W., W. Giles, P. Greengard: Cyclic AMP mediates the effects of adrenaline on cardiac Purkinje fibres, Nature new Biol.240, 181–183 (1972).PubMedGoogle Scholar
  13. 13.
    Watanabe, A. M., H. R. Besh: Subcellular myocardial effects of verapamil and D 600: Comparison with propranolol. J. Pharmac. exp. Ther.191, 241–251 (1974).Google Scholar
  14. 14.
    Yamasaki, Y., M. Fujiwara, N. Toda: Effects of intracellularly applied cyclic 3′,5′-adenosine monophosphate and dibutyryl cyclic 3′,5′-adenosine monophosphate on the electrical activity of sino-atrial nodal cells of the rabbit. J. Pharmac. exp. Ther.190, 15–20 (1974).Google Scholar

Copyright information

© Dr. Dietrich Steinkopff Verlag 1980

Authors and Affiliations

  • T. Podzuweit
    • 1
  1. 1.MRC Neurochemistry Research GroupUniversity of StellenboschTygerbergSouth Africa

Personalised recommendations