Conduction slowing contributes to spontaneous ventricular arrhythmias in intrinsically active murine RyR2-P2328S hearts.
J Cardiovasc Electrophysiol
; 24(2): 210-8, 2013 Feb.
Article
en En
| MEDLINE
| ID: mdl-23131176
ABSTRACT
INTRODUCTION:
The familial condition catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by episodic bidirectional ventricular tachycardia (BVT), polymorphic ventricular tachycardia (PVT), and ventricular fibrillation following adrenergic challenge. It is associated with mutations involving the cardiac ryanodine receptor (RyR2). METHODS ANDRESULTS:
We explored for a slowing of myocardial conduction that could potentially result in a substrate for the spontaneous arrhythmogenesis that was observed following introduction of isoproterenol and caffeine in intrinsically beating murine RyR2-P2328S hearts. Such pharmacological challenge increased the number of arrhythmic episodes in electrocardiographic recordings from intact anesthetized mice, with the greatest effects in the homozygote RyR2(S/S). Arrhythmias took the form of bigeminy, BVT, monomorphic ventricular tachycardia, and PVT, as found in human CPVT. Ventricular epicardial conduction velocities (CVs) measured using multielectrode array recordings and maximum action potential upstroke rates, (dV/dt)(max), measured using intracellular microelectrodes were indistinguishable in untreated wild-type (WT) and RyR2(S/S). Pharmacological challenge of RyR2(S/S), but not WT hearts, then reduced CV and (dV/dt)(max) and also revealed a strongly arrhythmic phenotype. There was no evidence of gross structural or fibrotic changes in either RyR2(+/S) or RyR2(S/S) hearts on light microscopy.CONCLUSIONS:
We associate altered ventricular myocardial CV potentially resulting in arrhythmogenic substrate with arrhythmic properties associated with genetic RyR2 alterations for the first time.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Taquicardia Ventricular
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Canal Liberador de Calcio Receptor de Rianodina
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Predisposición Genética a la Enfermedad
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Sistema de Conducción Cardíaco
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Conducción Nerviosa
Límite:
Animals
Idioma:
En
Revista:
J Cardiovasc Electrophysiol
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
FISIOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Reino Unido