Copyright © 1993 by the European Society of Cardiology.
© 1993 The European Society of Cardiology
Early after-depolarizations and torsade de pointes: Implications for the control of cardiac arrhythmias by prolonging repolarization
Vanderbilt University, Nashville Tennesse, U.S.A.
Correspondence: Dan M. Roden, MD. Vanderbilt University, Director, Division of Clinical Pharmacology, 532C Medical Research Building, Nashville, TN 37232-6602, U.S.A.
Common clinical features in drug-induced torsade de pointes include hypokalemia and cycle-length prolongation just prior to initiation of the arrhythmia. In canine Purkinje fibres, drugs known to be associated with torsade de pointes, such as quinidine, sotalol or N-acetylprocainamide, consistently produce early after-depolarizations (EADs) and triggered activity at slow drive rates; for quinidine, these abnormalities are exaggerated by low extracellular potassium. Triggered activity can be abolished in vitro in two ways. First, action-potential shortening with abolition of EADs can be accomplished by increasing stimulation rates, beta-stimulation and action-potential shortening antiarrhythmics such as lidocaine. Second, triggered activity can be suppressed, with less prominent effects on EADs, by magnesium, alpha- and/or beta-adrenergic blockade and calcium-channel blockers. The parallels between these in vitro findings and clinical torsade depointes suggest that EADs and triggered activity play a role in the genesis of the clinical arrhythmia. Further research directed at determining the mechanisms underlying the cellular abnormalities and their propagation to the whole heart should yield information that will increase the safety of antiarrhythmic therapy.
Key Words: Long QT syndromes • after-depolarizations • ventricular tachycardia • torsade de pointes
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Wang, R. W. Joyner, M. B. Wagner, J. Cheng, D. Lai, and B. H. Crawford Stretch-activated channel activation promotes early afterdepolarizations in rat ventricular myocytes under oxidative stress Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1227 - H1235. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Gordon, G. Panaghie, L. Deng, K. J. Bee, T. K. Roepke, T. Krogh-Madsen, D. J. Christini, H. Ostrer, C. T. Basson, W. Chung, et al. A KCNE2 mutation in a patient with cardiac arrhythmia induced by auditory stimuli and serum electrolyte imbalance Cardiovasc Res, January 1, 2008; 77(1): 98 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Poelzing and R. Veeraraghavan Heterogeneous ventricular chamber response to hypokalemia and inward rectifier potassium channel blockade underlies bifurcated T wave in guinea pig Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H3043 - H3051. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. V. Pham and M. R. Rosen Sex, hormones, and repolarization Cardiovasc Res, February 15, 2002; 53(3): 740 - 751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. O Verkerk, M. W Veldkamp, R. Coronel, R. Wilders, and A. C.G van Ginneken Effects of cell-to-cell uncoupling and catecholamines on Purkinje and ventricular action potentials: implications for phase-1b arrhythmias Cardiovasc Res, July 1, 2001; 51(1): 30 - 40. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A P Beelen, K-T. Yeo, and L D Lewis Asymptomatic QTc prolongation associated with quetiapine fumarate overdose in a patient being treated with risperidone Human and Experimental Toxicology, April 1, 2001; 20(4): 215 - 219. [Abstract] [PDF]
|
|
|
|
 |
|
 J. Merot, V. Probst, M. Debailleul, U. Gerlach, N. S. Moise, H. Le Marec, and F. Charpentier Electropharmacological characterization of cardiac repolarization in German shepherd dogs with an inherited syndrome of sudden death: abnormal response to potassium channel blockers J. Am. Coll. Cardiol., September 1, 2000; 36(3): 939 - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C Viswanathan and Y. Rudy Pause induced early afterdepolarizations in the long QT syndrome: a simulation study Cardiovasc Res, May 1, 1999; 42(2): 530 - 542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Reyes, R. Khatib, G. Khatib, K.L. Ho, F. Smith, and R. A. Kloner Prolonged Captopril Therapy in Murine Viral Myocarditis Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1998; 3(1): 43 - 49. [Abstract] [PDF]
|
|
|
|
|
|
A. Bril, M.-C. Forest, B. Cheval, and J.-F. Faivre Combined potassium and calcium channel antagonistic activities as a basis for neutral frequency dependent increase in action potential duration: comparison between BRL-32872 and azimilide Cardiovasc Res, January 1, 1998; 37(1): 130 - 140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|