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

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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


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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


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



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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.
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