Ryanodine-receptor inhibition by dantrolene effectively suppresses ventricular arrhythmias in an ex vivo model of long-QT syndrome.
J Cardiovasc Electrophysiol
; 29(3): 471-476, 2018 03.
Article
em En
| MEDLINE
| ID: mdl-29314443
ABSTRACT
AIMS:
A significant antiarrhythmic potential of ryanodine receptor inhibition was reported in experimental studies. The aim of the present study was to assess potential antiarrhythmic effects of dantrolene in an experimental whole-heart model of drug-induced long-QT syndrome (LQTS).METHODS:
In 12 isolated rabbit hearts, long-QT-2-syndrome was simulated by infusion of erythromycin (300 µM). Twelve rabbit hearts were treated with veratridine (0.5 µM) to mimic long-QT-3-syndrome.RESULTS:
Monophasic action potentials and ECG showed a significant prolongation of QT-interval (+71 ms, P < 0.01) and action potential duration (APD, +43 ms, P < 0.01) after infusion of erythromycin as compared with baseline. Similar results were obtained in veratridine-treated hearts (QT-interval +43 ms, P < 0.01; APD +36 ms, P < 0.01). Both erythromycin (+36 ms, P < 0.05) and veratridine (+38 ms) significantly increased dispersion of repolarization. Additional infusion of dantrolene (20 µM) did not significantly alter QT-interval and APD but resulted in a significant reduction of dispersion of repolarization (erythromycin group -33 ms, P < 0.05; veratridine group -29 ms, P < 0.05). Lowering of potassium concentration resulted in the occurrence of early afterdepolarizations (EAD) and polymorphic ventricular tachycardia (VT) in 9 of 12 erythromycin-treated hearts (175 episodes) and 8 of 12 veratridine-treated hearts (66 episodes). Additional infusion of dantrolene significantly reduced occurrence of polymorphic VT and resulted in occurrence of EAD and polymorphic VT in 1 of 12 erythromycin-treated hearts (18 episodes) and 1 of 12 veratridine-treated hearts (3 episodes).CONCLUSION:
Inhibition of the ryanodine receptor by dantrolene significantly reduced occurrence of polymorphic VT in drug-induced LQTS. A significant reduction of spatial dispersion of repolarization represents a major antiarrhythmic mechanism. These results imply that dantrolene may represent a promising antiarrhythmic option in drug-induced LQTS.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Síndrome do QT Longo
/
Bloqueadores dos Canais de Cálcio
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Torsades de Pointes
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Canal de Liberação de Cálcio do Receptor de Rianodina
/
Dantroleno
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Frequência Cardíaca
/
Ventrículos do Coração
/
Antiarrítmicos
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Cardiovasc Electrophysiol
Assunto da revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
FISIOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Alemanha