Drug-induced post-repolarization refractoriness as an antiarrhythmic principle and its underlying mechanism.
Europace
; 16 Suppl 4: iv39-iv45, 2014 Nov.
Article
en En
| MEDLINE
| ID: mdl-25362169
ABSTRACT
AIMS:
We hypothesized that amiodarone (AM), unlike d-sotalol (DS) (a 'pure' Class III agent), not only prolongs the action potential duration (APD) but also causes post-repolarization refractoriness (PRR), thereby preventing premature excitation and providing superior antiarrhythmic efficacy. METHODS ANDRESULTS:
We tested this hypothesis in 31 patients with inducible ventricular tachycardia (VT) during programmed stimulation with the use of the 'Franz' monophasic action potential (MAP) catheter with simultaneous pacing capability. We determined the effective refractory period (ERP) for each of three extrastimuli (S2-S4) and the corresponding MAP duration at 90% repolarization (APD90), both during baseline and on randomized therapy with either DS (n = 15) or AM (n = 16). We defined ERP > APD90 as PRR and ERP < APD90 as 'encroachment' on repolarization. A revised computer action potential model was developed to help explain the mechanisms of these in-vivo human-heart phenomena. Encroachment but not PRR was present in all patients at baseline and during DS treatment (NS vs. baseline), and VT was non-inducible in only 2 of 15 DS patients. In contrast, in 12 of 16 AM patients PRR was present (P < 0.001 vs. baseline), and VT was no longer inducible. Our model (with revised sodium channel kinetics) reproduced encroachment and drug-induced PRR.CONCLUSION:
Both, AM and DS, prolonged APD90 but only AM produced PRR and prevented encroachment of premature extrastimuli. Our computer simulations suggest that PRR is due to altered kinetics of the slow inactivation of the rapid sodium current. This may contribute to the high antiarrhythmic efficacy of AM.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Periodo Refractario Electrofisiológico
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Sotalol
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Canales de Sodio
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Taquicardia Ventricular
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Bloqueadores de los Canales de Sodio
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Sistema de Conducción Cardíaco
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Frecuencia Cardíaca
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Amiodarona
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Antiarrítmicos
Tipo de estudio:
Clinical_trials
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Diagnostic_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Europace
Asunto de la revista:
CARDIOLOGIA
/
FISIOLOGIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos