Broad antiarrhythmic effect of mexiletine in different arrhythmia models.
Europace
; 20(8): 1375-1381, 2018 08 01.
Article
em En
| MEDLINE
| ID: mdl-29016765
ABSTRACT
Aims:
Experimental studies and clinical reports suggest antiarrhythmic properties of mexiletine in different arrhythmias. We aimed at investigating mexiletine in experimental models of atrial fibrillation (AF) as well as in long-QT- (LQTS) and short-QT-syndrome (SQTS). Methods andresults:
In 15 isolated rabbit hearts, erythromycin (300 µM) was infused for simulation of long-QT-2-syndrome. In further 13 hearts, veratridine was administered to simulate long-QT-3-syndrome. Both drugs induced a significant QT-prolongation (erythromycin +87 ms, P < 0.01; veratridine +19 ms, P < 0.05) and increased dispersion of repolarization (erythromycin +55 ms, P < 0.01; veratridine +31 ms, P < 0.01). Additional infusion of mexiletine (25 µM) resulted in a significant reduction of dispersion (erythromycin -43 ms, P < 0.01; veratridine -26 ms, P < 0.05). Reproducible induction of torsade de pointes was observed in 13 of 15 erythromycin-treated hearts (192 episodes) and 6 of 13 veratridine-treated hearts (36 episodes). Additional infusion of mexiletine significantly reduced ventricular tachycardia (VT) incidence. With mexiletine, only 3 of 15 erythromycin-treated hearts (27 episodes) and 1 of 13 veratridine-treated hearts (2 episodes) presented polymorphic VT. In additional 9 hearts, the IK-ATP-channel-opener pinacidil was employed to simulate SQTS and significantly abbreviated ventricular repolarization (QT-interval -18 ms, P < 0.05) and enhanced induction of ventricular fibrillation (VF). Mexiletine reversed the effects of pinacidil, increase refractory period (+127 ms, P < 0.01) and significantly suppressed induction of VF. In further 13 hearts AF was induced by combined treatment with acetylcholine/isoproterenol. Mexiletine also increased atrial refractory period (+80 ms, P < 0.01) and thereby effectively suppressed atrial fibrillation.Conclusion:
Acute infusion of mexiletine significantly reduced the occurrence of polymorphic VT in the presence of pharmacologically simulated LQTS. Furthermore, mexiletine demonstrated potent antiarrhythmic properties in a model of SQTS and in AF.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Arritmias Cardíacas
/
Fibrilação Atrial
/
Síndrome do QT Longo
/
Taquicardia Ventricular
/
Sistema de Condução Cardíaco
/
Frequência Cardíaca
/
Mexiletina
/
Antiarrítmicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Europace
Assunto da revista:
CARDIOLOGIA
/
FISIOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Alemanha