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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

Summary

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.

Keywords

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

Zusammenfassung

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.

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Copyright information

© Dr. Dietrich Steinkopff Verlag 1980

Authors and Affiliations

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

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