Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Más filtros

Bases de datos
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Cardiovasc Ther ; 35(2)2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28039911

RESUMEN

INTRODUCTION: The antihistaminic antazoline (ANT) was reported to be highly effective and safe for rapid conversion of atrial fibrillation (AF). We therefore analyzed underlying mechanisms in an experimental whole-heart model. METHODS AND RESULTS: Isolated and retrogradely perfused rabbit hearts underwent a standardized protocol employing atrial burst pacing-induced AF in five of 20 hearts under baseline conditions (seven episodes). Thereafter, a combination of acetylcholine and isoproterenol was employed to enhance AF occurrence. Two monophasic action potential recordings on the left- and two on the right atrial epicardium showed a decrease in atrial action potential duration (aAPD, -25 msec, P<.05) and atrial effective refractory period (aERP; -52 msec, P<.01) after infusion of acetylcholine (1 µmol/L) and isoproterenol (1 µmol/L). This led to induction of AF in 14 of 20 hearts (145 episodes). Simultaneous infusion of ANT (20 µmol/L) led to a complete suppression of AF in all inducible hearts. Treatment with ANT also led to a significant increase in aAPD (+41 msec, P<.01) and aERP (+74 msec, P<.05), leading to a marked increase in atrial postrepolarization refractoriness (aPRR, +33 msec, P<.01). Results were compared to 13 rabbits treated with flecainide. Flecainide induced a significant increase in aPRR and resulted in induction of AF in seven of 13 hearts (51 episodes) while 11 of 13 hearts were inducible with acetylcholine and isoproterenol (93 episodes). CONCLUSION: Administration of ANT was highly effective in suppressing AF. The antiarrhythmic effect could be explained by a significant increase in postrepolarization refractoriness as a result of a more marked increase in aERP as compared with aAPD.


Asunto(s)
Antazolina/farmacología , Antiarrítmicos/farmacología , Fibrilación Atrial/prevención & control , Frecuencia Cardíaca/efectos de los fármacos , Antagonistas de los Receptores Histamínicos H1/farmacología , Acetilcolina , Potenciales de Acción , Animales , Fibrilación Atrial/inducido químicamente , Fibrilación Atrial/fisiopatología , Estimulación Cardíaca Artificial , Relación Dosis-Respuesta a Droga , Descubrimiento de Drogas , Electrocardiografía , Técnicas Electrofisiológicas Cardíacas , Flecainida/farmacología , Preparación de Corazón Aislado , Isoproterenol , Conejos , Periodo Refractario Electrofisiológico , Factores de Tiempo
2.
Europace ; 16(8): 1240-8, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24696223

RESUMEN

AIM: The most recent European Society of Cardiology (ESC) update on atrial fibrillation has introduced vernakalant (VER) for pharmacological cardioversion of atrial fibrillation. The aim of the present study was to investigate the safety profile of VER in a sensitive model of proarrhythmia. METHODS AND RESULTS: In 36 Langendorff-perfused rabbit hearts, VER (10, 30 µM, n = 12); ranolazine (RAN, 10, 30 µM, n = 12), or sotalol (SOT, 50; 100 µM, n = 12) were infused after obtaining baseline data. Monophasic action potentials and a 12-lead electrocardiogram showed a significant QT prolongation after application of VER as compared with baseline (10 µM: +25 ms, 30 µM: +50 ms, P < 0.05) accompanied by an increase of action potential duration (APD). The increase in APD90 was accompanied by a more marked increase in effective refractory period (ERP) leading to a significant increase in post-repolarization refractoriness (PRR, 10 µM: +30 ms, 30 µM: +36 ms, P < 0.05). Vernakalant did not affect the dispersion of repolarization. Lowered potassium concentration in bradycardic hearts did not provoke early afterdepolarizations (EADs) or polymorphic ventricular tachycardia (pVT). Comparable results were obtained with RAN. Hundred micromolars of SOT led to an increase in QT interval (+49 ms) and APD90 combined with an increased ERP and PRR (+23 ms). In contrast to VER, 100 µM SOT led to a significant increase in dispersion of repolarization and to the occurrence of EAD in 10 of 12 and pVT in 8 of 12 hearts. CONCLUSION: In the present study, application of VER and SOT led to a comparable prolongation of myocardial repolarization. Both drugs increased the PRR. However, VER neither affect the dispersion of repolarization nor induce EAD and therefore did not cause proarrhythmia.


Asunto(s)
Anisoles/toxicidad , Antiarrítmicos/toxicidad , Arritmias Cardíacas/inducido químicamente , Técnicas Electrofisiológicas Cardíacas , Sistema de Conducción Cardíaco/efectos de los fármacos , Pirrolidinas/toxicidad , Acetanilidas/toxicidad , Potenciales de Acción , Animales , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatología , Sistema de Conducción Cardíaco/fisiopatología , Técnicas In Vitro , Modelos Animales , Perfusión , Piperazinas/toxicidad , Bloqueadores de los Canales de Potasio/toxicidad , Conejos , Ranolazina , Medición de Riesgo , Factores de Riesgo , Bloqueadores de los Canales de Sodio/toxicidad , Sotalol/toxicidad , Factores de Tiempo
3.
Heart Rhythm ; 7(12): 1862-9, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20728579

RESUMEN

BACKGROUND: Patients with long QT syndrome (LQTS) are at increased risk not only for ventricular arrhythmias but also for atrial pathology including atrial fibrillation (AF). Some patients with "lone" AF carry Na(+)-channel mutations. OBJECTIVE: The purpose of this study was to determine the mechanisms underlying atrial pathology in LQTS. METHODS: In mice with a heterozygous knock-in long QT syndrome type 3 (LQT3) mutant of the cardiac Na(+) channel (ΔKPQ-SCN5A) and wild-type (WT) littermates, atrial size, function, and electrophysiologic parameters were measured in intact Langendorff-perfused hearts, and histologic analysis was performed. RESULTS: Atrial action potential duration, effective refractory period, cycle length, and PQ interval were prolonged in ΔKPQ-SCN5A hearts (all P < .05). Flecainide (1 µM) reversed atrial action potential duration prolongation and induced postrepolarization refractoriness (P < .05). Arrhythmias were infrequent during regular rapid atrial rate in both WT and ΔKPQ-SCN5A but were inducible in 15 (38%) of 40 ΔKPQ-SCN5A and 8 (29%) of 28 WT mice upon extrastimulation. Pacing protocols generating rapid alterations in rate provoked atrial extrasystoles and arrhythmias in 6 (66%) of 9 ΔKPQ-SCN5A but in 0 (0%) of 6 WT mice (P < .05). Atrial diameter was increased by nearly 10% in ΔKPQ-SCN5A mice > 5 months old without increase in fibrotic tissue. CONCLUSION: Murine hearts bearing an LQT3 mutation show abnormalities in atrial electrophysiology and subtle changes in atrial dimension, including an atrial arrhythmogenic phenotype on provocation. These results support clinical data suggesting that LQTS mutations can cause atrial pathology and arrhythmogenesis and indicate that murine sodium channel LQTS models may be useful for exploring underlying mechanisms.


Asunto(s)
Atrios Cardíacos/fisiopatología , Activación del Canal Iónico/genética , Síndrome de QT Prolongado/genética , Síndrome de QT Prolongado/fisiopatología , Canales de Sodio/genética , Potenciales de Acción/fisiología , Animales , Antiarrítmicos/farmacología , Fibrilación Atrial/genética , Fibrilación Atrial/fisiopatología , Ecocardiografía Doppler , Técnicas Electrofisiológicas Cardíacas , Femenino , Fibrosis , Flecainida/farmacología , Técnicas de Sustitución del Gen , Atrios Cardíacos/patología , Técnicas In Vitro , Masculino , Ratones , Ratones Transgénicos , Mutación , Canal de Sodio Activado por Voltaje NAV1.5 , Recuperación de la Función/genética
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA