Accelerated Sinus Rhythm Prevents Catecholaminergic Polymorphic Ventricular Tachycardia in Mice and in Patients

RATIONALE:Catecholaminergic polymorphic ventricular tachycardia (CPVT) is caused by mutations in cardiac ryanodine receptor (RyR2) or calsequestrin (Casq2) genes. Sinoatrial node dysfunction associated with CPVT may increase the risk for ventricular arrhythmia (VA). OBJECTIVE:To test the hypothesis...

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Bibliographic Details
Published in:Circulation research 2013-02, Vol.112 (4), p.689-697
Main Authors: Faggioni, Michela, Hwang, Hyun Seok, van der Werf, Christian, Nederend, Ineke, Kannankeril, Prince J, Wilde, Arthur A.M, Knollmann, Björn C
Format: Article
Language:English
Subjects:
Adult
Animals
Atropine - pharmacology
Atropine - therapeutic use
Bradycardia - genetics
Bradycardia - physiopathology
Caffeine - toxicity
Calcium Signaling - physiology
Calsequestrin - deficiency
Calsequestrin - genetics
Calsequestrin - physiology
Cardiac Pacing, Artificial
Exercise Test
Heart Rate - drug effects
Humans
Isoproterenol - toxicity
Mice
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - physiology
Random Allocation
Ryanodine Receptor Calcium Release Channel - deficiency
Ryanodine Receptor Calcium Release Channel - genetics
Ryanodine Receptor Calcium Release Channel - physiology
Sinoatrial Node - physiopathology
Sympathectomy, Chemical
Tachycardia, Ventricular
Vagus Nerve - drug effects
Vagus Nerve - physiopathology
Ventricular Premature Complexes - etiology
Ventricular Premature Complexes - prevention & control
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Summary:RATIONALE:Catecholaminergic polymorphic ventricular tachycardia (CPVT) is caused by mutations in cardiac ryanodine receptor (RyR2) or calsequestrin (Casq2) genes. Sinoatrial node dysfunction associated with CPVT may increase the risk for ventricular arrhythmia (VA). OBJECTIVE:To test the hypothesis that CPVT is suppressed by supraventricular overdrive stimulation. METHODS AND RESULTS:Using CPVT mouse models (Casq2 and RyR2 mice), the effect of increasing sinus heart rate was tested by pretreatment with atropine and by atrial overdrive pacing. Increasing intrinsic sinus rate with atropine before catecholamine challenge suppressed ventricular tachycardia in 86% of Casq2 mice (6/7) and significantly reduced the VA score (atropine0.6±0.2 versus vehicle1.7±0.3; P
ISSN:0009-7330
1524-4571
DOI:10.1161/CIRCRESAHA.111.300076