Expertos Invitados





MECANISMOS CELULARES Y MOLECULARES SUBYACENTES DE LAS ARRITMIAS CARDIACAS INDUCIDAS POR DROGAS Y ASOCIADAS CON LA PROLONGACION DEL INTERVALO QT

(especial para SIIC © Derechos reservados)
Los datos actuales sugieren que el problema principal en los síndromes congénitos y adquiridos de QT prolongado no es el alargamiento del intervalo QT sino la dispersión de la repolarización que habitualmente acompaña esta prolongación.
Autor:
Charles Antzelevitch
Columnista Experto de SIIC

Institución:
Masonic Medical Research Laboratory

Artículos publicados por Charles Antzelevitch
Coautor
Serge Sicouri, MD* 
Masonic Medical Research Laboratory*
Recepción del artículo
17 de Enero, 2005 		Aprobación
17 de Enero, 2005
Primera edición
24 de Enero, 2006 		Segunda edición, ampliada y corregida
7 de Junio, 2021

MECANISMOS CELULARES Y MOLECULARES SUBYACENTES DE LAS ARRITMIAS CARDIACAS INDUCIDAS POR DROGAS Y ASOCIADAS CON LA PROLONGACION DEL INTERVALO QT

Resumen
La prolongación del intervalo QT en ocasiones se asocia con torsade de pointes (TdP), arritmias que ponen en riesgo la vida, que se desarrollan como consecuencia de la amplificación de heterogeneidades eléctricas propias del miocardio ventricular. Estas existen debido a las diferencias en el tiempo de repolarización de los tres tipos celulares predominantes que conforman el miocardio ventricular, las que dan origen a gradientes de voltaje transmural y a una dispersión de la repolarización responsable del registro de la onda T en el electrocardiograma (ECG). Las drogas y los trastornos que reducen la corriente de repolarización neta producen una prolongación preferencial del potencial de acción de la célula M y de esta forma amplifican la dispersión espacial intrínseca de la repolarización, lo que crea el sustrato para la reentrada. El resultado es la prolongación del intervalo QT, ondas T anormales y la aparición de taquicardia ventricular polimórfica por reentrada que muestra características de TdP. Estos trastornos también predisponen a extrasístoles inducidas por posdespolarizaciones tempranas de las células M y las fibras de Purkinje, las cuales se cree desencadenan los episodios de TdP. Una reducción de la corriente de repolarización neta, de esta manera, aporta el sustrato y el mecanismo desencadenante para el inicio de la arritmia por reentrada que se cree yace en la TdP. Los agentes que prolongan el intervalo QT pero que no incrementan la dispersión transmural de la repolarización, como pentobarbital sódico, amiodarona y ranolazina, por lo general no inducen TdP. Los datos disponibles sugieren que el problema principal tanto en los síndromes congénitos y adquiridos de QT prolongado no es el alargamiento del intervalo QT, sino la dispersión de la repolarización que habitualmente acompaña su prolongación.

Palabras clave
Síndrome de QT prolongado, dispersión de la repolarización, torsade de pointes


Artículo completo
(castellano)
Extensión:  +/-19.26 páginas impresas en papel A4
Exclusivo para suscriptores/assinantes

CELLULAR AND MOLECULAR MECHANISMS UNDERLYING DRUG-INDUCED CARDIAC ARRHYTHMIAS ASSOCIATED WITH PROLONGATION OF THE QT INTERVAL

Abstract
Drug-induced QT prolongation is sometimes associated with life-threatening torsade de pointes (TdP) arrhythmias that develop as a consequence of the amplification of electrical heterogeneities intrinsic to the ventricular myocardium. These heterogeneities exist because of differences in the time course of repolarization of the three predominant cell types that comprise the ventricular myocardium, giving rise to transmural voltage gradients and a dispersion of repolarization responsible for the inscription of the T wave in the electrocardiogram (ECG). Drugs and conditions that reduce net repolarizing current produce a preferential prolongation of the M cell action potential and thus amplify the intrinsic spatial dispersion of repolarization, creating the substrate for the development of reentry. The result is a prolongation of the QT interval, abnormal T waves and the development of polymorphic reentrant ventricular tachycardia displaying characteristics of TdP. These conditions also predispose M cells and Purkinje fibers to develop early afterdepolarization (EAD)-induced extrasystoles, which are thought to trigger the episodes of TdP. A reduction of net repolarizing current thus provides both the substrate and trigger for the initiation of the reentrant arrhythmia believed to underlie TdP. Agents that prolong the QT interval but do not increase transmural dispersion of repolarization, including sodium pentobarbital, amiodarone and ranolazine, generally do not induce TdP. The available data suggest that that the principal problem with both acquired and congenital long QT syndromes is not long QT intervals, but rather the dispersion of repolarization that often accompanies prolongation of the QT interval.

Key words
Long QT syndrome, dispersion of repolarization, torsade de pointes


Full text
(english)
 para suscriptores/ assinantes
Clasificación en siicsalud
Artículos originales > Expertos del Mundo >
página   www.siicsalud.com/des/expertocompleto.php/

Especialidades
Principal: Cardiología, Farmacología
Relacionadas: Bioquímica, Diagnóstico por Imágenes, Diagnóstico por Laboratorio, Medicina Interna



Comprar este artículo
Extensión: 19.26 páginas impresas en papel A4

file05.gif (1491 bytes) Artículos seleccionados para su compra




Patrocinio y reconocimiento:
El trabajo fue subsidiado por los National Institutes of Health (HL 47678), American Heart Association, Northeast Affiliate, y the Masons of New York State and Florida.
Bibliografía del artículo
  1. Mayer AG. Rhythmical pulsations is scyphomedusae. Publication 47 of the Carnegie Institute 1906; 1-62.
  2. Mayer AG. Rhythmical pulsations in scyphomedusae. II. Publication 102 of the Carnegie Institute 1908; 115-131.
  3. Mines GR. On dynamic equilibrium in the heart. J Physiol 1913; 46:349-382.
  4. Mines GR. On circulating excitations in heart muscles and their possible relation to tachycardia and fibrillation. Trans R Soc Can 1914; 8:43-52.
  5. Lewis T. The broad features and time-relations of the normal electrocardiogram. Principles of interpretation. The mechanism and graphic registration of the heart beat. London: Shaw & sons, Ltd., 1925:44-77.
  6. Moe GK. Evidence for reentry as a mechanism for cardiac arrhythmias. Rev Physiol Biochem Pharmacol 1975; 72:55-81.
  7. Kulbertus HE. In: Kulbertus HE, editor. Reentrant Arrhythmias, Mechanisms and Treatment. Baltimore: University Park Press, 1977.
  8. Wit AL, Cranefield PF. Re-entrant excitation as a cause of cardiac arrhythmias. Am J Physiol 1978; 235:H1-H17.
  9. Wit AL, Allessie MA, Fenoglic JJ, Jr., Bonke FIM, Lammers W, Smeets J. Significance of the endocardial and epicardial border zones in the genesis of myocardial infarction arrhythmias. In: Harrison D, editor. Cardiac Arrhythmias: A Decade of Progress. Boston: GK Hall, 1982: 39-68.
  10. Spear JF, Moore EN. Mechanisms of cardiac arrhythmias. Annu Rev Physiol 1982; 44:485-497.
  11. Janse MJ. Reentry rhythms. In: Fozzard HA, Haber E, Jennings RB, Katz AM, Morgan HE, editors. The Heart and Cardiovascular System. New York: Raven Press, 1986: 1203-1238.
  12. Hoffman BF, Dangman KH. Mechanisms for cardiac arrhythmias. Experientia 1987; 43:1049-1056.
  13. Antzelevitch C. Reflection as a mechanism of reentrant cardiac arrhythmias. Prog Cardiol 1988; 1:3-16.
  14. El-Sherif N. Reentry revisited. PACE 1988; 11:1358-1368.
  15. Lazzara R, Scherlag BJ. Generation of arrhythmias in myocardial ischemia and infarction. Am J Cardiol 1988; 61:20A-26A.
  16. Rosen MR. The links between basic and clinical cardiac electrophysiology. Circulation 1988; 77:251-263.
  17. Antzelevitch C, Brugada P, Brugada J, Brugada R, Towbin JA, Nademanee K. Brugada syndrome: 1992-2002. A historical perspective. J Am Coll Cardiol 2003; 41(10):1665-1671.
  18. Antzelevitch C, Brugada P, Brugada J et al. Brugada Syndrome. A Decade of Progress. Circ Res 2002; 91(12):1114-1119.
  19. Antzelevitch C, Shimizu W. Cellular mechanisms underlying the Long QT syndrome. Curr Opin Cardiol 2002; 17(1):43-51.
  20. Bednar MM, Harrigan EP, Anziano RJ, Camm AJ, Ruskin JN. The QT interval. Prog Cardiovasc Dis 2001; 43(5 Pt 2):1-45.
  21. Gwathmey JK, Slawsky MT, Briggs GM, Morgan JP. Role of intracellular sodium in the regulation of intracellular calcium and contractility. Effects of DPI 201-106 on excitation- contraction coupling in human ventricular myocardium. J Clin Invest 1988; 82:1592-1605.
  22. Li CZ, Wang HW, Liu JL, Liu K, Yang ZF, Liu YM. [Effect of ATXII on opening modes of myocyte sodium channel, action potential and QT intervals of ECG]. Sheng Li Xue Bao 2001; 53(2):111-116.
  23. Hanck DA, Sheets MF. Modification of inactivation in cardiac sodium channels: Ionic current studies with anthopleurin-A toxin. J Gen Physiol 1995; 106:601-616.
  24. Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med 2004; 350(10):1013-1022.
  25. Fenichel RR, Malik M, Antzelevitch C et al. Drug-induced Torsade de Pointes and implications for drug development. J Cardiovasc Electrophysiol 2004; 15:1-21.
  26. Belardinelli L, Antzelevitch C, Vos MA. Assessing Predictors of drug-induced Torsade de Pointes. Trends Pharmacol Sci 2003; 24:619-625.
  27. Antzelevitch C, El-Sherif N, Rosenbaum D, Vos M. Cellular mechanisms underlying the long QT syndrome. J Cardiovasc Electrophysiol 2003; 14(1):114-115.
  28. Haverkamp W, Breithardt G, Camm AJ et al. The potential for QT prolongation and pro-arrhythmia by non-anti- arrhythmic drugs: Clinical and regulatory implications. Report on a Policy Conference of the European Society of Cardiology. Cardiovasc Res 2000; 47(2):219-233.
  29. Selzer A, Wray HW. Quinidine syncope. Paroxysmal ventricular fibrillation occurring during treatment of chronic atrial arrhythmias. Circulation 1964; 30:17-26.
  30. Roden DM, Woosley RL, Primm RK. Incidence and clinical features of the quinidine-associated long- QT syndrome: Implications for patient care. Am Heart J 1986; 111:1088-1093.
  31. Kay GN, Plumb VJ, Arciniegas JG, Henthorn RW, Waldo AL. Torsade de Pointes: The long-short initiating sequence and other clinical features: observations in 32 patients. J Am Coll Cardiol 1983; 2:806-817.
  32. Haverkamp W, Martinez-Rubio A, Hief C et al. Efficacy and safety of d,l-sotalol in patients with ventricular tachycardia and in survivors of cardiac arrest. J Am Coll Cardiol 1997; 30:487-495.
  33. Lehmann MH, Hardy S, Archibald D, Quart B, Macneil DJ. Sex difference in risk of torsade de pointes with d,l-sotalol. Circulation 1996; 94:2535-2541.
  34. Hohnloser SH. Proarrhythmia with class III antiarrhythmic drugs: types, risks, and management. Am J Cardiol 1997; 80(8A):82G-89G.
  35. Kober L, Bloch Thomsen PE, Moller M et al. Effect of dofetilide in patients with recent myocardial infarction and left-ventricular dysfunction: a randomised trial. Lancet 2000; 356(9247):2052-2058.
  36. Stambler BS, Wood MA, Ellenbogen KA, Perry KT, Wakefield LK, VanderLugt JT. Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation. Ibutilide Repeat Dose Study Investigators. Circulation 1996; 94(7):1613-1621.
  37. Antzelevitch C. Heterogeneity of cellular repolarization in LQTS: the role of M cells. Eur Heart J 2001; Supplements 3:K-2-K-16.
  38. Antzelevitch C, Nesterenko VV, Muzikant AL, Rice JJ, Chen G, Colatsky TJ. Influence of transmural repolarization gradients on the electrophysiology and pharmacology of ventricular myocardium. Cellular basis for the Brugada and long-QT syndromes. Philos Trans R Soc Lond [Biol] 2001; 359:1201-1216.
  39. Antzelevitch C, Dumaine R. Electrical heterogeneity in the heart: Physiological, pharmacological and clinical implications. In: Page E, Fozzard HA, Solaro RJ, editors. Handbook of Physiology. Section 2 The Cardiovascular System. New York: Oxford University Press, 2001: 654-692.
  40. Weissenburger J, Nesterenko VV, Antzelevitch C. Transmural heterogeneity of ventricular repolarization under baseline and long QT conditions in the canine heart in vivo: Torsades de Pointes develops with halothane but not pentobarbital anesthesia. J Cardiovasc Electrophysiol 2000; 11:290-304.
  41. Antzelevitch C, Shimizu W, Yan GX et al. The M cell: Its contribution to the ECG and to normal and abnormal electrical function of the heart. J Cardiovasc Electrophysiol 1999; 10(8):1124-1152.
  42. Kozhevnikov DO, Yamamoto K, Robotis D, Restivo M, El-Sherif N. Electrophysiological mechanism of enhanced susceptibility of hypertrophied heart to acquired torsade de pointes arrhythmias: tridimensional mapping of activation and recovery patterns. Circulation 2002; 105(9):1128-1134.
  43. Vos MA, van Opstal JM, Leunissen JD, Verduyn SC. Electrophysiologic parameters and predisposing factors in the generation of drug-induced Torsade de Pointes arrhythmias. Pharmacol Ther 2001; 92(2-3):109-122.
  44. Akar FG, Yan GX, Antzelevitch C, Rosenbaum DS. Unique topographical distribution of M cells underlies reentrant mechanism of torsade de pointes in the long-QT syndrome. Circulation 2002; 105(10):1247-1253.
  45. Sicouri S, Antzelevitch C. A subpopulation of cells with unique electrophysiological properties in the deep subepicardium of the canine ventricle. The M cell. Circ Res 1991; 68:1729-1741.
  46. Zygmunt AC, Eddlestone GT, Thomas GP, Nesterenko VV, Antzelevitch C. Larger late sodium conductance in M cells contributes to electrical heterogeneity in canine ventricle. Am J Physiol 2001; 281:H689-H697.
  47. Liu DW, Antzelevitch C. Characteristics of the delayed rectifier current (IKr and IKs) in canine ventricular epicardial, midmyocardial, and endocardial myocytes. Circ Res 1995; 76:351-365.
  48. Zygmunt AC, Goodrow RJ, Antzelevitch C. INa-Ca contributes to electrical heterogeneity within the canine ventricle. Am J Physiol 2000; 278:H1671-H1678.
  49. Antzelevitch C, Zygmunt AC, Dumaine R. Electrophysiology and pharmacology of ventricular repolarization. In: Gussak I, Antzelevitch C, editors. Cardiac Repolarization. Bridging Basic and Clinical Sciences. Totowa: Humana Press, NJ, 2003: 63-90.
  50. Yan GX, Antzelevitch C. Cellular basis for the normal T wave and the electrocardiographic manifestations of the long QT syndrome. Circulation 1998; 98:1928-1936.
  51. Cohen IS, Giles WR, Noble D. Cellular basis for the T wave of the electrocardiogram. Nature 1976; 262:657-661.
  52. Einthoven W. Uber die Deutung des Electrokardiogramms. Pflugers Arch 1912; 149:65-86.
  53. Zuckerman R, Cabrera-Cosio E. La ondu U. Arch Inst Cardiol Mex 1947; 17:521-532.
  54. Furbetta D, Bufalari A, Santucci F, Solinas P. Abnormality of the U wave and the T-U segment of the electrocardiogram: The syndrome of the papillary muscles. Circulation 1956; 14:1129-1137.
  55. Nahum LH, Hoff HE. The interpretation of the U wave of the electrocardiogram. Am Heart J 1939; 17:585-598.
  56. Lepeschkin E. Genesis of the U wave. Circulation 1957; 15:77-81.
  57. Hoffman BF, Cranefield PF. Electrophysiology of the heart. New York: McGraw-Hill, 1960.
  58. Watanabe Y. Purkinje repolarization as a possible cause of the U wave in the electrocardiogram. Circulation 1975; 51:1030-1037.
  59. Lab MJ. Contraction-excitation feedback in myocardium: Physiologic basis and clinical revelance. Circ Res 1982; 50:757-766.
  60. Choo MH, Gibson DG. U waves in ventricular hypertrophy: possible demonstration of mechano-electrical feedback. Br Heart J 1986; 55:428-433.
  61. Antzelevitch C, Nesterenko VV, Yan GX. Role of M cells in acquired long QT syndrome, U waves, and torsade de pointes. J Electrocardiol 1996; 28(suppl.):131-138.
  62. Shimizu W, Antzelevitch C. Sodium channel block with mexiletine is effective in reducing dispersion of repolarization and preventing Torsade de Pointes in LQT2 and LQT3 models of the long-QT syndrome. Circulation 1997; 96:2038-2047.
  63. Lehmann MH, Suzuki F, Fromm BS et al. T-wave "humps" as a potential electrocardiographic marker of the long QT syndrome. J Am Coll Cardiol 1994; 24:746-754.
  64. Surawicz B. U wave: facts, hypotheses, misconceptions, and misnomers. J Cardiovasc Electrophysiol 1998; 9(10):1117-1128.
  65. Shimizu W, Antzelevitch C. Cellular basis for the ECG features of the LQT1 form of the long QT syndrome: Effects of b-adrenergic agonists and antagonists and sodium channel blockers on transmural dispersion of repolarization and Torsade de Pointes. Circulation 1998; 98:2314-2322.
  66. Schwartz PJ, Priori SG, Spazzolini C et al. Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation 2001; 103(1):89-95.
  67. Li GR, Feng J, Yue L, Carrier M. Transmural heterogeneity of action potentials and Ito1 in myocytes isolated from the human right ventricle. Am J Physiol 1998; 275:H369-H377.
  68. Shimizu W, Antzelevitch C. Differential effects of beta-adrenergic agonists and antagonists in LQT1, LQT2 and LQT3 models of the long QT syndrome. J Am Coll Cardiol 2000; 35:778-786.
  69. Balser JR, Bennett PB, Hondeghem LM, Roden DM. Suppression of time-dependent outward current in guinea-pig ventricular myocytes. Actions of quinidine and amiodarone. Circ Res 1991; 69:519-529.
  70. Anyukhovsky EP, Sosunov EA, Feinmark SJ, Rosen MR. Effects of quinidine on repolarization in canine epicardium, midmyocardium, and endocardium. II. In vivo study. Circulation 1997; 96:4019-4026.
  71. Shimizu W, McMahon B, Antzelevitch C. Sodium pentobarbital reduces transmural dispersion of repolarization and prevents torsade de pointes in models of acquired and congenital long QT syndrome. J Cardiovasc Electrophysiol 1999; 10:156-164.
  72. Sun ZQ, Eddlestone GT, Antzelevitch C. Ionic mechanisms underlying the effects of sodium pentobarbital to diminish transmural dispersion of repolarization. Pacing and Clinical Electrophysiology 20, 11-1116. 1997.
  73. Sicouri S, Moro S, Litovsky SH, Elizari MV, Antzelevitch C. Chronic amiodarone reduces transmural dispersion of repolarization in the canine heart. J Cardiovasc Electrophysiol 1997; 8:1269-1279.
  74. van Opstal JM, Schoenmakers M, Verduyn SC et al. Chronic Amiodarone evokes no Torsade de Pointes arrhythmias despite QT lengthening in an animal model of acquired Long-QT Syndrome. Circulation 2001; 104(22):2722-2727.
  75. Zygmunt AC, Thomas GP, Belardinelli L, Blackburn B, Antzelevitch C. Ranolazine produces ion channel effects similar to those observed with chronic amiodarone in canine cardiac ventricular myocytes. Pacing Clin.Electrophysiol 25, II-626. 2002.
  76. Antzelevitch C, Belardinelli L, Wu L et al. Electrophysiologic Properties of Ranolazine: A Novel Anti-Anginal Agent. J Cardiovasc Pharmacol Therapeut. In press.
  77. Yang T, Snyders D, Roden DM. Drug block of I(kr): model systems and relevance to human arrhythmias. J Cardiovasc Pharmacol 2001; 38(5):737-744.
  78. Carlsson L, Almgren O, Duker GD. Qtu-Prolongation and Torsades-de-Pointes Induced by Putative Class-III Antiarrhythmic Agents in the Rabbit - Etiology and Interventions. J Cardiovasc Pharmacol 1990; 16:276-285.
  79. Lu HR, Remeysen P, De Clerck F. Nonselective I(Kr)-blockers do not induce torsades de pointes in the anesthetized rabbit during alpha1-adrenoceptor stimulation. J Cardiovasc Pharmacol 2000; 36(6):728-736.
  80. Vos MA, De Groot SH, Verduyn SC et al. Enhanced susceptibility for acquired torsade de pointes arrhythmias in the dog with chronic, complete AV block is related to cardiac hypertrophy and electrical remodeling. Circulation 1998; 98(11):1125-1135.
  81. Sugiyama A, Satoh Y, Shiina H, Takeda S, Hashimoto K. Torsadegenic action of the antipsychotic drug sulpiride assessed using in vivo canine models. J Cardiovasc Pharmacol 2002; 40(2):235-245.
  82. Weissenburger J, Chezalviel F, Davy JM et al. Methods and limitations of an experimental model of long QT syndrome. J Pharm Methods 1991; 26:23-42.
  83. Weissenburger J, Davy JM, Chezalviel F et al. Arrhythmogenic activities of antiarrhythmic drugs in conscious hypokalemic dogs with atrioventricular block: comparison between quinidine, lidocaine, flecainide, propranolol and sotalol. J Pharmacol Exp Ther 1991; 259:871-883.
  84. Emori T, Antzelevitch C. Cellular basis for complex T waves and arrhythmic activity following combined I(Kr) and I(Ks) block. J Cardiovasc Electrophysiol 2001; 12(12):1369-1378.
  85. Lubinski A, Lewicka-Nowak E, Kempa M, Baczynska AM, Romanowska I, Swiatecka G. New insight into repolarization abnormalities in patients with congenital long QT syndrome: the increased transmural dispersion of repolarization. PACE 1998; 21:172-175.
  86. Wolk R, Stec S, Kulakowski P. Extrasystolic beats affect transmural electrical dispersion during programmed electrical stimulation. Eur J Clinical Invest 2001; in press.
  87. Tanabe Y, Inagaki M, Kurita T et al. Sympathetic stimulation produces a greater increase in both transmural and spatial dispersion of repolarization in LQT1 than LQT2 forms of congenital long QT syndrome. J Am Coll Cardiol 2001; 37:911-919.
  88. Frederiks J, Swenne CA, Kors JA et al. Within-subject electrocardiographic differences at equal heart rates: role of the autonomic nervous system. Pflugers Arch 2001; 441(5):717-724.
  89. Yamaguchi M, Shimizu M, Ino H et al. T wave peak-to-end interval and QT dispersion in acquired long QT syndrome: a new index for arrhythmogenicity. Clin Sci (Lond) 2003; 105:671-676.
  90. van Opstal JM, Verduyn SC, Winckels SK et al. The JT-area indicates dispersion of repolarization in dogs with atrioventricular block. J Interv Card Electrophysiol 2002; 6(2):113-120.
  91. Donger C, Denjoy I, Berthet M et al. KVLQT1 C-terminal missense mutation causes a forme fruste long-QT syndrome. Circulation 1997; 96(9):2778-2781.
  92. Napolitano C, Schwartz PJ, Brown AM et al. Evidence for a cardiac ion channel mutation underlying drug-induced QT prolongation and life-threatening arrhythmias [In Process Citation]. J Cardiovasc Electrophysiol 2000; 11(6):691-696.
  93. Yang P, Kanki H, Drolet B et al. Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes. Circulation 2002; 105(16):1943-1948.
  94. Abbott GW, Sesti F, Splawski I et al. MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell 1999; 97:175-187.
  95. Splawski I, Timothy KW, Tateyama M et al. Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmia. Science 2002; 297(5585):1333-1336.
  96. Ford GA, Wood SM, Daly AK. CYP2D6 and CYP2C19 genotypes of patients with terodiline cardiotoxicity identified through the yellow card system. Br J Clin Pharmacol 2000; 50(1):77-80.
  97. Roden DM. Pharmacogenetics and drug-induced arrhythmias. Cardiovasc Res 2001; 50(2):224-231.
  98. Carmeliet E. Use-dependent block and use-dependent unblock of the delayed rectifier K+ current by almokalant in rabbit ventricular myocytes. Circ Res 1993; 73:857-868.
  99. Houltz B, Darpo B, Edvardsson N et al. Electrocardiographic and clinical predictors of torsades de pointes induced by almokalant infusion in patients with chronic atrial fibrillation or flutter: a prospective study. PACE 1998; 21(5):1044-1057.
  100. Carlsson L, Drews L, Duker GD, Schiller-Linhardt G. Attenuation of proarrhythmias related to delayed repolarization by low-dose lidocaine in the anesthetized rabbit. J Pharmacol Exp Ther 1993; 267:1076-1080.
  101. Wiesfeld AC, Crijns HJ, Bergstrand RH, Almgren O, Hillege HL, Lie KI. Torsades de pointes with Almokalant, a new class III antiarrhythmic drug. Am Heart J 1993; 126(4):1008-1011.
  102. Abrahamsson C, Carlsson L, Duker G. Lidocaine and nisoldipine attenuate almokalant-induced dispersion of repolarization and early afterdepolarizations in vitro. J Cardiovasc Electrophysiol 1996; 7(11):1074-1081.
  103. Verduyn SC, Vos MA, Van der Zande J, Kulcsar A, Wellens HJ. Further observations to elucidate the role of interventricular dispersion of repolarization and early afterdepolarizations in the genesis of acquired torsade de pointes arrhythmias: a comparison between almokalant and d-sotalol using the dog as its own control. J Am Coll Cardiol 1997; 30:1575-1584.
  104. Kiehn J, Thomas D, Karle CA, Schols W, Kubler W. Inhibitory effects of the class III antiarrhythmic drug amiodarone on cloned HERG potassium channels. Naunyn Schmiedebergs Arch Pharmacol 1999; 359(3):212-219.
  105. Kodama I, Kamiya K, Toyama J. Amiodarone: ionic and cellular mechanisms of action of the most promising class III agent. Am J Cardiol 1999; 84(9A):20R-28R.
  106. Hii JT, Wyse DG, Gillis AM, Duff HJ, Solylo MA, Mitchell LB. Precordial QT interval dispersion as a marker of torsade de pointes. Disparate effects of class Ia antiarrhythmic drugs and amiodarone. Circulation 1992; 86(5):1376-1382.
  107. Hohnloser SH, Klingenheben T, Singh BN. Amiodarone-associated proarrhythmic effects. A review with special reference to torsade de pointes tachycardia. Ann Intern Med 1994; 121:529-535.
  108. Merot J, Charpentier F, Poirier JM, Coutris G, Weissenburger J. Effects of chronic treatment by amiodarone on transmural heterogeneity of canine ventricular repolarization in vivo: interactions with acute sotalol. Cardiovasc Res 1999; 44(2):303-314.
  109. Drouin E, Lande G, Charpentier F. Amiodarone reduces transmural heterogeneity of repolarization in the human heart. J Am Coll Cardiol 1998; 32(4):1063-1067.
  110. Fermini B, Jurkiewicz NK, Jow B et al. Use-dependent effects of the class III antiarrhythmic agent NE-10064 (azimilide) on cardiac repolarization: block of delayed rectifier potassium and L-type calcium currents. J Cardiovasc Pharmacol 1995; 26(2):259-271.
  111. Busch AE, Eigenberger B, Jurkiewicz NK et al. Blockade of HERG channels by the class III antiarrhythmic azimilide: mode of action. Br J Pharmacol 1998; 123(1):23-30.
  112. Yan GX, Wu Y, Liu T, Wang J, Marinchak RA, Kowey PR. Phase 2 early afterdepolarization as a trigger of polymorphic ventricular tachycardia in acquired long-qt syndrome : direct evidence from intracellular recordings in the intact left ventricular wall. Circulation 2001; 103(23):2851-2856.
  113. Van Opstal JM, Leunissen JD, Wellens HJ, Vos MA. Azimilide and dofetilide produce similar electrophysiological and proarrhythmic effects in a canine model of Torsade de Pointes arrhythmias. Eur J Pharmacol 2001; 412(1):67-76.
  114. Connolly SJ, Schnell DJ, Page RL, Wilkinson WE, Marcello SR, Pritchett EL. Dose-response relations of azimilide in the management of symptomatic, recurrent, atrial fibrillation. Am J Cardiol 2001; 88(9):974-979.
  115. Kiehn J, Lacerda AE, Wible BA, Brown AM. Molecular physiology and pharmacology of HERG single-channel currents and block by dofetilide. Circulation 1996; 94:2572-2579.
  116. Yang T, Roden DM. Extracellular potassium modulation of drug block of IKr. Implications for torsade de pointes and reverse use-dependence. Circulation 1996; 93:407-411.
  117. Buchanan LV, Kabell GG, Brunden MN, Gibson JK. Comparative assessment of ibutilide, D-sotalol, clofilium, E- 4031, and UK-68,798 in a rabbit model of proarrhythmia. J Cardiovasc Pharmacol 1993; 22:540-549.
  118. Torp-Pedersen C, Moller M, Bloch-Thomsen PE et al. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. N Engl J Med 1999; 341(12):857-865.
  119. Yang T, Snyders DJ, Roden DM. Ibutilide, a methanesulfonanilide antiarrhythmic, is a potent blocker of the rapidly activating delayed rectifier K+ current (IKr) in AT-1 cells. Concentration-, time-, voltage-, and use- dependent effects. Circulation 1995; 91:1799-1806.
  120. Ellenbogen KA, Stambler BS, Wood MA et al. Efficacy of intravenous ibutilide for rapid termination of atrial fibrillation and atrial flutter: a dose-response study. J Am Coll Cardiol 1996; 28(1):130-136.
  121. Glatter K, Yang Y, Chatterjee K et al. Chemical Cardioversion of Atrial Fibrillation or Flutter With Ibutilide in Patients Receiving Amiodarone Therapy. Circulation 2001; 103(2):253-257.
  122. Po SS, Wang DW, Yang IC, Johnson JP, Jr., Nie L, Bennett PB. Modulation of HERG potassium channels by extracellular magnesium and quinidine. J Cardiovasc Pharmacol 1999; 33(2):181-185.
  123. Bauman JL, Bauernfeind RA, Hoff JV, Strasberg B, Swiryn S, Rosen KM. Torsade de pointes due to quinidine: Observations in 31 patients. Am Heart J 1984; 107:425-430.
  124. Roden DM, Hoffman BF. Action potential prolongation and induction of abnormal automaticity by low quinidine concentrations in canine Purkinje fibers. Relationship to potassium and cycle length. Circ Res 1985; 56(6):857-867.
  125. Sicouri S, Antzelevitch C. Drug-induced afterdepolarizations and triggered activity occur in a discrete subpopulation of ventricular muscle cell (M cells) in the canine heart: Quinidine and Digitalis. J Cardiovasc Electrophysiol 1993; 4:48-58.
  126. Carmeliet E. Electrophysiologic and voltage clamp analysis of the effects of sotalol on isolated cardiac muscle and Purkinje fibers. J Pharmacol Exp Ther 1985; 232:817-825.
  127. Varro A, Balati B, Iost N et al. The role of the delayed rectifier component IKs in dog ventricular muscle and Purkinje fibre repolarization. J Physiol (Lond) 2000; 523 Pt 1:67-81.
  128. Eckardt L, Breithardt G, Haverkamp W. Electrophysiologic characterization of the antipsychotic drug sertindole in a rabbit heart model of torsade de pointes: low torsadogenic potential despite QT prolongation. J Pharmacol Exp Ther 2002; 300(1):64-71.
  129. McKibbin JK, Pocock WA, Barlow JB, Millar RN, Obel IW. Sotalol, hypokalaemia, syncope, and torsade de pointes. Br Heart J 1984; 51(2):157-162.
  130. Patterson E, Scherlag BJ, Lazzara R. Early afterdepolarizations produced by d,l-sotalol and clofilium. J Cardiovasc Electrophysiol 1997; 8:667-678.
  131. Sicouri S, Moro S, Elizari MV. d-Sotalol induces marked action potential prolongation and early afterdepolarizations in M but not epicardial or endocardial cells of the canine ventricle . J Cardiovasc Pharmacol Ther 1997; 2:27-38.
  132. Suessbrich H, Waldegger S, Lang F, Bush AE. Blockade of HERG channels expressed in Xenopus oocytes by the histamine receptor antagonists terfenadine and astemizoles. FEBS Lett 1996; 385:77-80.
  133. Delpon E, Valenzuela C, Tamargo J. Blockade of cardiac potassium and other channels by antihistamines. Drug Saf 1999; 21 Suppl 1:11-18.
  134. Salata JJ, Jurkiewicz NK, Wallace AA, Stupienski RF, Guinosso PJ, Lynch JJ. Cardiac electrophysiological actions of the histamine H1-receptor antagonists astemizole and terfenadine compared with chlorpheniramine and pyrilamine. Circ Res 1995; 76:110-119.
  135. Sakemi H, VanNatta B. Torsade de pointes induced by astemizole in a patient with prolongation of the QT interval. Am Heart J 1993; 125(5):1436-1438.
  136. Tsai WC, Tsai LM, Chen JH. Combined use of astemizole and ketoconazole resulting in torsade de pointes. J Formos Med Assoc 1997; 96(2):144-146.
  137. Weissenburger J, Noyer M, Cheymol G, Jaillon P. Electrophysiological effects of cetirizine, astemizole and D-sotalol in a canine model of long QT syndrome. Clin Exp Allergy 1999; 29 Suppl 3:190-196.
  138. Pratt CM, Hertz RP, Ellis BE, Crowell SP, Louv W, Moye L. Risk of developing Life-Threatening ventricular arrhythmia associated with terfenadine in comparison with over-the-Counter antihistamines, ibuprofen and clemastine. Am J Cardiol 1994; 73:346-352.
  139. Pratt CM, Ruberg S, Morganroth J et al. Dose-response relation between terfenadine (Seldane) and the QTc interval on the scalar electrocardiogram: Distinguishing a drug effect from spontaneous variability. Am Heart J 1996; 131:472-480.
  140. Monahan BP, Ferguson CL, Killeavy ES, Lloyd BK. Torsades de pointes occurring in association with terfenadine use. JAMA 1990; 264(21):2788-2790.
  141. Zimmermann M, Duruz H, Guinand O, Broccard O. Torsades de pointes after treatment with terfenadine and ketoconazole. Eur Heart J 1992; 13(7):1002-1003.
  142. Daleau P, Lessard E, Groleau MF, Turgeon J. Erythromycin blocks the rapid component of the delayed rectifier potassium current and lengthens repolarization of guinea pig ventricular myocytes. Circulation 1995; 91:3010-3016.
  143. Rampe D, Murawsky MK. Blockade of the human cardiac K+ channel Kv1.5 by the antibiotic erythromycin. Naunyn Schmiedebergs Arch Pharmacol 1997; 355(6):743-750.
  144. Antzelevitch C, Sun ZQ, Zhang ZQ, Yan GX. Cellular and ionic mechanisms underlying erythromycin-induced long QT intervals and torsade de pointes. J Am Coll Cardiol 1996; 28:1836-1848.
  145. Oberg KC, Bauman JL. QT interval prolongation and torsades de pointes due to erythromycin lactobionate. Pharmacotherapy 1995; 15(6):687-692.
  146. Gitler B, Berger LS, Buffa SD. Torsades de pointes induced by erythromycin. Chest 1994; 105:368-372.
  147. Fazekas T, Krassoi I, Lengyel C, Varro A, Papp JG. Suppression of erythromycin-induced early afterdepolarizations and torsade de pointes ventricular tachycardia by mexiletine. PACE 1998; 21:147-150.
  148. Nattel S, Talajic M, Lemery R, Roy D. Erythromycin induced long QT syndrome: concordance with quinidine and underlying cellular electrophysiologic mechanism. Am J Med 1990; 89:235-238.
  149. Zhang S, Zhou Z, Gong Q, Makielski JC, January CT. Mechanism of block and identification of the verapamil binding domain to HERG potassium channels. Circ Res 1999; 84(9):989-998.
  150. Hollifield JW, Heusner JJ, DesChamps M et al. Comparison of equal-weight oral dosages of verapamil hydrochloride and diltiazem hydrochloride in patients with mild to moderate hypertension. Clin Pharm 1988; 7(2):129-134.
  151. Funck-Brentano C, Coudray P, Planellas J, Motte G, Jaillon P. Effects of Bepridil and Diltiazem on Ventricular Repolarization in Angina Pectoris. Am J Cardiol 1990; 66:812-817.
  152. Singh BN. Comparative efficacy and safety of bepridil and diltiazem in chronic stable angina pectoris refractory to diltiazem. The Bepridil Collaborative Study Group. Am J Cardiol 1991; 68(4):306-312.
  153. Chouabe C, Drici MD, Romey G, Barhanin J. Effects of calcium channel blockers on cloned cardiac K+ channels IKr and IKs. Therapie 2000; 55(1):195-202.
  154. De Cicco M, Macor F, Robieux I et al. Pharmacokinetic and pharmacodynamic effects of high-dose continuous intravenous verapamil infusion: clinical experience in the intensive care unit. Crit Care Med 1999; 27(2):332-339.
  155. Gonzalez-Gomez A, Cires PM, Gamio CF, Rodriguez dl, V, Garcia-Barreto D. Relationships between verapamil plasma concentrations and its antihypertensive action. Int J Clin Pharmacol Ther Toxicol 1988; 26(9):453-460.
  156. Boutarin J, Maarek-Charbit M, Aupetit JF, Galey-Arcangioli C, Ritz B. [Efficacy and tolerability of isoptine LP in mild to moderate hypertension. A multicenter study with 50 patients]. Ann Cardiol Angeiol (Paris) 1992; 41(10):587-593.
  157. Bril A, Gout B, Bonhomme M et al. Combined potassium and calcium channel blocking activities as a basis for antiarrhythmic efficacy with low proarrhythmic risk: experimental profile of BRL-32872. J Pharmacol Exp Ther 1996; 276:637-646.
  158. Benardeau A, Weissenburger J, Hondeghem LM, Ertel EA. Effects of the T-type Ca(2+) channel blocker mibefradil on repolarization of guinea pig, rabbit, dog, monkey, and human cardiac tissue. J Pharmacol Exp Ther 2000; 292(2):561-575.
  159. Glaser S, Steinbach M, Opitz C, Wruck U, Kleber FX. Torsades de pointes caused by Mibefradil. Eur J Heart Fail 2001; 3(5):627-630.
  160. Pinto JM, Sosunov EA, Gainullin RZ, Rosen MR, Boyden PA. Effects of mibefradil, a T-type calcium current antagonist, on electrophysiology of Purkinje fibers that survived in the infarcted canine heart. J Cardiovasc Electrophysiol 1999; 10(9):1224-1235.
  161. Rowland E, McKenna WJ, Krikler DM. Electrophysiologic and antiarrhythmic actions of bepridil. Comparison with verapamil and ajmaline for atrioventricular reentrant tachycardia. Am J Cardiol 1985; 55(13 Pt 1):1513-1519.
  162. Manouvrier J, Sagot M, Caron C et al. Nine cases of torsade de pointes with bepridil administration. Am Heart J 1986; 111(5):1005-1007.
  163. Osaka T, Kodama I, Toyama J, Yamada K. Effects of bepridil on ventricular depolarization and repolarization of rabbit isolated hearts with particular reference to its possible proarrhythmic properties. Br J Pharmacol 1988; 93(4):775-780.
  164. Prystowsky EN. Electrophysiologic and antiarrhythmic properties of bepridil. Am J Cardiol 1985; 55(7):59C-62C.
  165. Campbell RM, Woosley RL, Iansmith DH, Roden DM. Lack of triggered automaticity despite repolarization abnormalities due to bepridil and lidoflazine. PACE 1990; 13:30-36.
  166. Rampe D, Murawsky MK, Grau J, Lewis EW. The antipsychotic agent sertindole is a high affinity antagonist of the human cardiac potassium channel HERG. J Pharmacol Exp Ther 1998; 286(2):788-793.
  167. Van Kammen DP, McEvoy JP, Targum SD, Kardatzke D, Sebree TB. A randomized, controlled, dose-ranging trial of sertindole in patients with schizophrenia. Psychopharmacology (Berl) 1996; 124(1-2):168-175.
  168. Zimbroff DL, Kane JM, Tamminga CA et al. Controlled, dose-response study of sertindole and haloperidol in the treatment of schizophrenia. Sertindole Study Group. Am J Psychiatry 1997; 154(6):782-791.
  169. Fritze J, Bandelow B. The QT interval and the atypical antipsychotic sertindole. Int J Psych Clinc Pract 1998; 2:265-273.
  170. Drolet B, Zhang S, Deschenes D et al. Droperidol lengthens cardiac repolarization due to block of the rapid component of the delayed rectifier potassium current. J Cardiovasc Electrophysiol 1999; 10(12):1597-1604.
  171. Lischke V, Behne M, Doelken P, Schledt U, Probst S, Vettermann J. Droperidol causes a dose-dependent prolongation of the QT interval. Anesth Analg 1994; 79(5):983-986.
  172. Guy JM, Andre-Fouet X, Porte J, Bertrand M, Lamaud M, Verneyre H. [Torsades de pointes and prolongation of the duration of QT interval after injection of droperidol]. Ann Cardiol Angeiol (Paris) 1991; 40(9):541-545.
  173. Michalets EL, Smith LK, Van Tassel ED. Torsade de pointes resulting from the addition of droperidol to an existing cytochrome P450 drug interaction. Ann Pharmacother 1998; 32(7-8):761-765.
  174. Adamantidis MM, Kerram P, Caron JF, Dupuis BA. Droperidol exerts dual effects on repolarization and induces early afterdepolarizations and triggered activity in rabbit purkinje fibers. J Pharmacol Exp Ther 1993; 266:884-893.
  175. Mohammad S, Zhou Z, Gong Q, January CT. Blockage of the HERG human cardiac K+ channel by the gastrointestinal prokinetic agent cisapride. Am J Physiol 1997; 273(5 Pt 2):H2534-H2538.
  176. Drolet B, Khalifa M, Daleau P, Hamelin BA, Turgeon J. 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 1998; 97(2):204-210.
  177. Wysowski DK, Bacsanyi J. Cisapride and fatal arrhythmia [letter]. N Engl J Med 1996; 335:290-291.
  178. Di Diego JM, Belardinelli L, Antzelevitch C. Cisapride-induced Transmural Dispersion of Repolarization and Torsade de Pointes in the Canine Left Ventricular Wedge Preparation During Epicardial Stimulation. Circulation 2003; 108:1027-1033.
  179. Chen YJ, Lee SH, Hsieh MH et al. Effects of 17beta-estradiol on tachycardia-induced changes of atrial refractoriness and cisapride-induced ventricular arrhythmia. J Cardiovasc Electrophysiol 1999; 10(4):587-598.
  180. Puisieux FL, Adamantidis MM, Dumotier BM, Dupuis BA. Cisapride-induced prolongation of cardiac action potential and early afterdepolarizations in rabbit Purkinje fibres. Br J Pharmacol 1996; 117:1377-1379.
  181. Le Grand B, Talmant JM, Rieu JP, Patoiseau JF, Colpaert FC, John GW. Investigation of the mechanism by which ketanserin prolongs the duration of the cardiac action potential. J Cardiovasc Pharmacol 1995; 26(5):803-809.
  182. Aldariz AE, Romero H, Baroni M, Baglivo H, Esper RJ. QT prolongation and torsade de pointes ventricular tachycardia produced by Ketanserin. PACE 1986; 9(6 Pt 1):836-841.
  183. Zaza A, Malfatto G, Rosen MR. Electrophysiologic effects of ketanserin on canine Purkinje fibers, ventricular myocardium and the intact heart. J Pharmacol Exp Ther 1989; 250:397-405.
  184. Antzelevitch C, Belardinelli L, Zygmunt AC et al. Electrophysiologic effects of ranolazine: A novel anti-anginal agent with antiarrhythmic properties. Circulation 2004; 110:904-910.
  185. Burashnikov A, Antzelevitch C. A combination of Ikr, Iks, and Ica or Ina block produces a relatively homogeneous prolongation of repolarization of cells spanning the canine left ventricular wall. Pacing and Clinical Electrophysiology 20, II-1216. 1997.
  186. Antzelevitch C, Shimizu W, Yan GX et al. The M cell: its contribution to the ECG and to normal and abnormal electrical function of the heart. J Cardiovasc Electrophysiol 1999; 10(8):1124-1152.
  187. Shimizu W, Antzelevitch C. Effects of a K(+) Channel Opener to Reduce Transmural Dispersion of Repolarization and Prevent Torsade de Pointes in LQT1, LQT2, and LQT3 Models of the Long-QT Syndrome. Circulation 2000; 102(6):706-712.
  188. Verduyn SC, Vos MA, Van der Zande J, Van der Hulst FF, Wellens HJ. Role of interventricular dispersion of repolarization in acquired torsade-de-pointes arrhythmias: reversal by magnesium. Cardiovasc Res 1997; 34:453-463.
 
 
 
 
 
 
 
 
 
 
 
 
Está expresamente prohibida la redistribución y la redifusión de todo o parte de los contenidos de la Sociedad Iberoamericana de Información Científica (SIIC) S.A. sin previo y expreso consentimiento de SIIC.
ua31618
Inicio/Home

Copyright siicsalud © 1997-2024 ISSN siicsalud: 1667-9008