Circulation, Vol 68, 846-856, Copyright © 1983 by American Heart Association
J Brachmann, BJ Scherlag, LV Rosenshtraukh and R Lazzara
We used cesium chloride (CsCl) for electrophysiologic studies in canine
hearts in vivo and in vitro to examine the mechanisms underlying
ventricular arrhythmias that are related to prolonged repolarization.
Cesium is known to depress normal ventricular automaticity and some
experimental arrhythmias by blocking delayed outward currents and
prolonging action potential duration. In 10 dogs in normal sinus rhythm, 1
to 1.5 mM/kg iv CsCl prolonged the QT (QU) interval and induced ventricular
ectopy in all, including multiform ventricular tachycardia. In 12 dogs with
atrioventricular block, 1 to 1.5 mM/kg iv CsCl produced marked suppression
of idioventricular rates (from 45 +/- 6 to 8 +/- 4 beats/min). These low
rates were then associated with bigeminy or bursts of multiform ventricular
arrhythmia. Pacing at rates of 60 beats/min or more suppressed these
arrhythmias. Low doses of tetrodotoxin (1 microgram/kg) also abolished
these bradycardia- dependent arrhythmias without affecting the amplitude of
ventricular electrograms. Tissue concentrations of cesium were determined
by anatomic absorption spectroscopy in five dogs after injection of 1 mM/kg
CsCl. Thirty minutes after the injection, cesium levels in Purkinje fibers
were 5.3 +/- 1.0 mM/kg, levels in ventricular muscle were 4.6 +/- 0.9
mM/kg, and levels in atrial muscle were 4.1 +/- 0.8 mM/kg. In eight
isolated endocardial preparations from canine ventricles, standard
microelectrode techniques were used to study the effects of superfusion
with 5 mM cesium. After 30 min, we observed early afterdepolarizations
interrupting phase 3 of Purkinje fiber action potentials that already
showed prolonged repolarization. Slowing the rate generated single or
multiple action potentials arising from partially repolarized levels of
membrane potentials (-80 to -65 mV). Pacing rates of 30 to 60 beats/min
diminished the afterdepolarizations and suppressed the spontaneous beats.
Tetrodotoxin at a concentration of 10(-8) g/ml, which did not affect
upstroke velocity, abolished the afterpotentials. We conclude that cesium
induced bradycardia-dependent ventricular arrhythmias caused by early
afterdepolarizations. These data suggest that an inward current, probably
carried by sodium ions, appears to be essential for the occurrence of this
phenomenon. The association of delayed repolarization,
afterdepolarizations, and triggered activity has similarities to the
phenomenon of drug-induced prolongation of the QTU interval associated with
multiform ventricular tachycardia in humans, i.e. "torsades de pointes."
ARTICLES
Bradycardia-dependent triggered activity: relevance to drug-induced multiform ventricular tachycardia
This article has been cited by other articles:
 |
|
 |
|
  Y. Mizukami, K. Ono, C.-K. Du, T. Aki, N. Hatano, Y. Okamoto, Y. Ikeda, H. Ito, K. Hamano, and S. Morimoto Identification and physiological activity of survival factor released from cardiomyocytes during ischaemia and reperfusion Cardiovasc Res, September 1, 2008; 79(4): 589 - 599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Morita, D. P. Zipes, S. T. Morita, and J. Wu Mechanism of U wave and polymorphic ventricular tachycardia in a canine tissue model of Andersen-Tawil syndrome Cardiovasc Res, August 1, 2007; 75(3): 510 - 518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ueda, K. Nakamura, T. Hayashi, N. Inagaki, M. Takahashi, T. Arimura, H. Morita, Y. Higashiuesato, Y. Hirano, M. Yasunami, et al. Functional Characterization of a Trafficking-defective HCN4 Mutation, D553N, Associated with Cardiac Arrhythmia J. Biol. Chem., June 25, 2004; 279(26): 27194 - 27198. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Roden Drug-Induced Prolongation of the QT Interval N. Engl. J. Med., March 4, 2004; 350(10): 1013 - 1022. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Rocchetti, A. Besana, G. Mostacciuolo, P. Ferrari, R. Micheletti, and A. Zaza Diverse Toxicity Associated with Cardiac Na+/K+ Pump Inhibition: Evaluation of Electrophysiological Mechanisms J. Pharmacol. Exp. Ther., May 1, 2003; 305(2): 765 - 771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kaab, M. Hinterseer, M. Nabauer, and G. Steinbeck Sotalol testing unmasks altered repolarization in patients with suspected acquired long-QT-syndrome--a case-control pilot study using i.v. sotalol Eur. Heart J., April 1, 2003; 24(7): 649 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. H.T. Wehrens, M. A. Vos, P. A. Doevendans, and H. J.J. Wellens Novel Insights in the Congenital Long QT Syndrome Ann Intern Med, December 17, 2002; 137(12): 981 - 992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Pinter, P. Dorian, and D. Newman Cesium-Induced Torsades de Pointes N. Engl. J. Med., January 31, 2002; 346(5): 383 - 384. [Full Text] [PDF]
|
|
|
|
 |
|
 M.R. Rosen Isolated tissue models and proarrhythmia Eur. Heart J. Suppl., September 1, 2001; 3(suppl_K): K64 - K69. [Abstract] [PDF]
|
|
|
|
|
|
S. S. Chugh, S. B. Johnson, and D. L. Packer Altered response to ibutilide in a heart failure model Cardiovasc Res, January 1, 2001; 49(1): 94 - 102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Rosen The Real Thing Circ. Res., July 7, 2000; 87(1): 6 - 7. [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Huelsing, K. W. Spitzer, and A. E. Pollard Electrotonic suppression of early afterdepolarizations in isolated rabbit Purkinje myocytes Am J Physiol Heart Circ Physiol, July 1, 2000; 279(1): H250 - H259. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. G.A. Volders, M. A. Vos, B. Szabo, K. R. Sipido, S.H.M. de Groot, A. P.M. Gorgels, H. J.J. Wellens, and R. Lazzara Progress in the understanding of cardiac early afterdepolarizations and torsades de pointes: time to revise current concepts Cardiovasc Res, June 1, 2000; 46(3): 376 - 392. [Full Text] [PDF]
|
|
|
|
|
|
E. A. Sosunov, R. Z. Gainullin, P. Danilo Jr., E. P. Anyukhovsky, M. Kirchengast, and M. R. Rosen Electrophysiological Effects of LU111995 on Canine Hearts: In Vivo and In Vitro Studies J. Pharmacol. Exp. Ther., July 1, 1999; 290(1): 146 - 152. [Abstract] [Full Text]
|
|
|
|
|
|
H. B. Nuss, S. Kaab, D. A. Kass, G. F. Tomaselli, and E. Marban Cellular basis of ventricular arrhythmias and abnormal automaticity in heart failure Am J Physiol Heart Circ Physiol, July 1, 1999; 277(1): H80 - H91. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. G. A. Volders, K. R. Sipido, M. A. Vos, A. Kulcsar, S. C. Verduyn, and H. J. J. Wellens Cellular Basis of Biventricular Hypertrophy and Arrhythmogenesis in Dogs With Chronic Complete Atrioventricular Block and Acquired Torsade de Pointes Circulation, September 15, 1998; 98(11): 1136 - 1147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Eckardt, W. Haverkamp, M. Borggrefe, and G. Breithardt Experimental models of torsade de pointes Cardiovasc Res, July 1, 1998; 39(1): 178 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nattel Experimental evidence for proarrhythmic mechanisms of antiarrhythmic drugs Cardiovasc Res, March 1, 1998; 37(3): 567 - 577. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-G. Li and S. H. Hohnloser Clinical Review : Update on Atrial Fibrillation: Restoration of Sinus Rhythm or Ventricular Rate Control? Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1998; 3(2): 185 - 194. [Abstract] [PDF]
|
|
|
|
 |
|
 H. Furushima, S. Niwano, M. Chinushi, K. Ohhira, A. Abe, and Y. Aizawa Relation between bradycardia dependent long QT syndrome and QT prolongation by disopyramide in humans Heart, January 1, 1998; 79(1): 56 - 58. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. P. Anyukhovsky, E. A. Sosunov, and M. R. Rosen Electrophysiologic Effects of Nibentan (HE-11) on Canine Cardiac Tissue J. Pharmacol. Exp. Ther., March 1, 1997; 280(3): 1137 - 1146. [Abstract] [Full Text]
|
|
|
|
|
|
C. Takanaka, K. O. Ogunyankin, J.S.M. Sarma, and B. N. Singh Antiarrhythmic and Arrhythmogenic Actions of Varying Levels of Extracellular Magnesium: Possible Cellular Basis for the Differences in the Efficacy of Magnesium and Lidocaine in Torsade de Pointes Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1997; 2(2): 125 - 134. [Abstract] [PDF]
|
|
|
|
|
|
D. M. Roden, R. Lazzara, M. Rosen, P. J. Schwartz, J. Towbin, and G. M. Vincent Multiple Mechanisms in the Long-QT Syndrome: Current Knowledge, Gaps, and Future Directions Circulation, October 15, 1996; 94(8): 1996 - 2012. [Abstract] [Full Text]
|
|
|
|
|
|
T. Satoh and D. P. Zipes Rapid Rates During Bradycardia Prolong Ventricular Refractoriness and Facilitate Ventricular Tachycardia Induction With Cesium in Dogs Circulation, July 15, 1996; 94(2): 217 - 227. [Abstract] [Full Text]
|
|
|
|
|
|
M. A. Vos, S. C. Verduyn, A. P.M. Gorgels, G. C. Lipcsei, and H. J.J. Wellens Reproducible Induction of Early Afterdepolarizations and Torsade de Pointes Arrhythmias by d-Sotalol and Pacing in Dogs With Chronic Atrioventricular Block Circulation, February 1, 1995; 91(3): 864 - 872. [Abstract] [Full Text]
|
|
|
|
|
|
M. Akhtar, H. Garan, M. H. Lehmann, and P. J. Troup Sudden Cardiac Death: Management of High-Risk Patients Ann Intern Med, March 15, 1991; 114(6): 499 - 512. [Abstract] [PDF]
|
|
|
|
|
|
R. Lazzara Amiodarone and Torsade de Pointes Ann Intern Med, October 1, 1989; 111(7): 549 - 551. [Abstract] [PDF]
|
|
|
|
|
|
T. A. Mattioni, T. A. Zheutlin, J. J. Sarmiento, M. Parker, M. Lesch, and R. F. Kehoe Amiodarone in Patients with Previous Drug-Mediated Torsade de Pointes: Long-Term Safety and Efficacy Ann Intern Med, October 1, 1989; 111(7): 574 - 580. [Abstract] [PDF]
|
|