Circulation Research, Vol 63, 286-305, Copyright © 1988 by American Heart Association

ARTICLES

QTU prolongation and polymorphic ventricular tachyarrhythmias due to bradycardia-dependent early afterdepolarizations. Afterdepolarizations and ventricular arrhythmias

N el-Sherif, RH Zeiler, W Craelius, WB Gough and R Henkin
Department of Medicine, State University of New York Health Science Center, Brooklyn 11203.

Polymorphic ventricular tachyarrhythmias occurred spontaneously during bradycardia in dogs given the inotropic polypeptide anthopleurin-A (AP- A). The arrhythmia was investigated in in vitro and in vivo experiments. In in vitro experiments, AP-A (50 micrograms/l) produced bradycardia-dependent prolongation of action potential duration that was more pronounced in Purkinje than in muscle fibers. Only Purkinje fibers developed early afterdepolarizations (EAD) and triggered activity. These effects could be abolished by rapid pacing, lidocaine (4 mg/l), or tetrodotoxin (1 mg/l). In vivo experiments were conducted in anesthetized healthy dogs with simultaneous recording of surface ECG, monophasic action potentials from the endocardial and epicardial surface of the left ventricle by contact electrode catheter technique, and transmembrane action potentials from the epicardial surface of the left ventricle with a floating microelectrode technique. AP-A in a dose comparable to that used in vitro (4 micrograms/kg, i.v. bolus) resulted in bradycardia-dependent marked prolongation of both monophasic and transmembrane action potentials. An EAD gradually appeared on both recordings but was more marked in endocardial monophasic action potentials. Eventually, a premature ventricular depolarization arose from or very close to the peak of the EAD. The prolongation of action potentials was associated with similar prolongation of the QTU interval in surface ECG, and in some experiments, the EAD corresponded to a distinct prominent U wave. A ventricular premature depolarization arose from the U or TU complex and initiated polymorphic ventricular tachyarrhythmias that terminated spontaneously or degenerated into ventricular fibrillation. These effects were reversed by rapid pacing or lidocaine (1 mg/kg). The present study provides evidence in support of the hypothesis that AP-A-induced ventricular tachyarrhythmias are due to bradycardia-dependent EAD and triggered activity.

This article has been cited by other articles:

				K. H. Haugaa, T. Edvardsen, T. P. Leren, J. M. Gran, O. A. Smiseth, and J. P. Amlie Left ventricular mechanical dispersion by tissue Doppler imaging: a novel approach for identifying high-risk individuals with long QT syndrome Eur. Heart J., February 1, 2009; 30(3): 330 - 337. [Abstract] [Full Text] [PDF]

				J. A. Wasserstrom, S. Kapur, S. Jones, T. Faruque, R. Sharma, J. E. Kelly, A. Pappas, W. Ho, A. H. Kadish, and G. L. Aistrup Characteristics of intracellular Ca2+ cycling in intact rat heart: a comparison of sex differences Am J Physiol Heart Circ Physiol, November 1, 2008; 295(5): H1895 - H1904. [Abstract] [Full Text] [PDF]

				E. B. Caref, M. Boutjdir, H. D. Himel, and N. El-Sherif Role of subendocardial Purkinje network in triggering torsade de pointes arrhythmia in experimental long QT syndrome Europace, October 1, 2008; 10(10): 1218 - 1223. [Abstract] [Full Text] [PDF]

				I. Topilski, O. Rogowski, R. Rosso, D. Justo, Y. Copperman, M. Glikson, B. Belhassen, M. Hochenberg, and S. Viskin The Morphology of the QT Interval Predicts Torsade de Pointes During Acquired Bradyarrhythmias J. Am. Coll. Cardiol., January 23, 2007; 49(3): 320 - 328. [Abstract] [Full Text] [PDF]

				M. Kondo, V. Nesterenko, and C. Antzelevitch Cellular basis for the monophasic action potential. Which electrode is the recording electrode? Cardiovasc Res, September 1, 2004; 63(4): 635 - 644. [Abstract] [Full Text] [PDF]

				B.-R. Choi, F. Burton, and G. Salama Cytosolic Ca2+ triggers early afterdepolarizations and torsade de pointes in rabbit hearts with type 2 long QT syndrome J. Physiol., September 1, 2002; 543(2): 615 - 631. [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]

				T. V Pham, R. B Robinson, P. Danilo Jr, and M. R Rosen Effects of gonadal steroids on gender-related differences in transmural dispersion of L-type calcium current Cardiovasc Res, February 15, 2002; 53(3): 752 - 762. [Abstract] [Full Text] [PDF]

				D. di Bernardo and A. Murray Origin on the electrocardiogram of U-waves and abnormal U-wave inversion Cardiovasc Res, January 1, 2002; 53(1): 202 - 208. [Abstract] [Full Text] [PDF]

				D. Babuty and M. J Lab Mechanoelectric contributions to sudden cardiac death Cardiovasc Res, May 1, 2001; 50(2): 270 - 279. [Full Text] [PDF]

				T. V. Pham, E. A. Sosunov, R. Z. Gainullin, P. Danilo Jr, and M. R. Rosen Impact of Sex and Gonadal Steroids on Prolongation of Ventricular Repolarization and Arrhythmias Induced by IK-Blocking Drugs Circulation, May 1, 2001; 103(17): 2207 - 2212. [Abstract] [Full Text] [PDF]

				J. F. Spear and E. N. Moore Modulation of arrhythmias by isoproterenol in a rabbit heart model of d-sotalol-induced long Q-T intervals Am J Physiol Heart Circ Physiol, July 1, 2000; 279(1): H15 - H25. [Abstract] [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]

				S Viskin, R Fish, D Zeltser, B Belhassen, K Heller, D Brosh, S Laniado, and H V Barron Arrhythmias in the congenital long QT syndrome: how often is torsade de pointes pause dependent? Heart, June 1, 2000; 83(6): 661 - 666. [Abstract] [Full Text]

				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]

				B. Drolet, F. Vincent, J. Rail, M. Chahine, D. Deschênes, S. Nadeau, M. Khalifa, B. A. Hamelin, and J. Turgeon Thioridazine Lengthens Repolarization of Cardiac Ventricular Myocytes by Blocking the Delayed Rectifier Potassium Current J. Pharmacol. Exp. Ther., March 1, 1999; 288(3): 1261 - 1268. [Abstract] [Full Text]

				M. E. Anderson, A. P. Braun, Y. Wu, T. Lu, Y. Wu, H. Schulman, and R. J. Sung KN-93, an Inhibitor of Multifunctional Ca++/Calmodulin-Dependent Protein Kinase, Decreases Early Afterdepolarizations in Rabbit Heart J. Pharmacol. Exp. Ther., December 1, 1998; 287(3): 996 - 1006. [Abstract] [Full Text]

				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]

				L Oikarinen, L Toivonen, and M Viitasalo Electrocardiographic measures of ventricular repolarisation dispersion in patients with coronary artery disease susceptible to ventricular fibrillation Heart, June 1, 1998; 79(6): 554 - 559. [Abstract] [Full Text]

				J. F. Spear and E. N. Moore Modulation of quinidine-induced arrhythmias by temperature in perfused rabbit heart Am J Physiol Heart Circ Physiol, March 1, 1998; 274(3): H817 - H828. [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]

				R. Dumaine and G. E. Kirsch Mechanism of lidocaine block of late current in long Q-T mutant Na+ channels Am J Physiol Heart Circ Physiol, February 1, 1998; 274(2): H477 - H487. [Abstract] [Full Text] [PDF]

				B. Drolet, M. Khalifa, P. Daleau, B. A. Hamelin, and J. Turgeon Block of the Rapid Component of the Delayed Rectifier Potassium Current by the Prokinetic Agent Cisapride Underlies Drug-Related Lengthening of the QT Interval Circulation, January 20, 1998; 97(2): 204 - 210. [Abstract] [Full Text] [PDF]

				N. El-Sherif, M. Chinushi, E. B. Caref, and M. Restivo Electrophysiological Mechanism of the Characteristic Electrocardiographic Morphology of Torsade de Pointes Tachyarrhythmias in the Long-QT Syndrome : Detailed Analysis of Ventricular Tridimensional Activation Patterns Circulation, December 16, 1997; 96(12): 4392 - 4399. [Abstract] [Full Text]

				S.C. Verduyn, M.A. Vos, J. van der Zande, F.F. van der Hulst, and H.J. Wellens Role of interventricular dispersion of repolarization in acquired torsade-de-pointes arrhythmias: reversal by magnesium Cardiovasc Res, June 1, 1997; 34(3): 453 - 463. [Abstract] [Full Text] [PDF]

				A. Lukas Electrophysiology of Myocardial Cells in the Epicardial, Midmyocardial, and Endocardial Layers of the Ventricle Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1997; 2(1): 61 - 72. [Abstract] [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]

				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]

				N. El-Sherif, E. B. Caref, H. Yin, and M. Restivo The Electrophysiological Mechanism of Ventricular Arrhythmias in the Long QT Syndrome: Tridimensional Mapping of Activation and Recovery Patterns Circ. Res., September 1, 1996; 79(3): 474 - 492. [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]

				R. Dumaine, Q. Wang, M. T. Keating, H. A. Hartmann, P. J. Schwartz, A. M. Brown, and G. E. Kirsch Multiple Mechanisms of Na+ Channel– Linked Long-QT Syndrome Circ. Res., May 1, 1996; 78(5): 916 - 924. [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]

				B. Nearing, A. Huang, and R. Verrier Dynamic tracking of cardiac vulnerability by complex demodulation of the T wave Science, April 19, 1991; 252(5004): 437 - 440. [Abstract] [PDF]