Journal article
Accelerated Junctional Rhythm and Nonalternans Repolarization Lability Precede Ventricular Tachycardia in Casq2−/− Mice
Journal of cardiovascular electrophysiology, Vol.23(12), pp.1355-1363
Manuscript received 25 March 2012; Revised manuscript received 22 May 2012; Accepted for publication 29 May 2012.
12/2012
DOI: 10.1111/j.1540-8167.2012.02406.x
PMID: 22860618
Abstract
Background: Calsequestrin-2 (CASQ2) is a Ca(2+) buffering protein of myocardial sarcoplasmic reticulum. CASQ2 mutations underlie a form of catecholaminergic polymorphic ventricular tachycardia (CPVT). The CPVT phenotype is recapitulated in Casq2 -/- mice. Repolarization lability (RL)-beat-to-beat variability in the T wave morphology-has been reported in long-QT syndrome, but has not been evaluated in CPVT.
Methods and results: ECG from Casq2 -/- mice was evaluated with respect to heart rate (HR) and RL changes prior to onset of ventricular tachycardia (VT) to gain insight into arrhythmogenesis in CPVT. Telemetry from unrestrained mice (3-month-old males, 5 animals of each genotype) and ECG before and after isoproterenol administration in anesthetized mice was analyzed. Average HR in sinus rhythm (SR), occurrence of nonsinus rhythm and RL were quantified. HR was slower in Casq2 -/- animals. Accelerated junctional rhythm (JR) occurred more frequently in Casq2 -/- mice and often preceded VT. In Casq2 -/- mice, HR increased prior to VT onset, prior to onset of JR and on transition from JR to VT. RL increased during progression from SR to VT and after isoproterenol administration in Casq2 -/-, but not in Casq2+/+ animals. Isoproterenol did not increase repolarization alternans in either genotype.
Conclusions: Accelerated JR, likely caused by triggered activity in His/Purkinje system, occurs frequently in Casq2 -/- mice. The absence of CASQ2 results in increased RL. The increase in HR and in RL precede onset of arrhythmias in this CPVT model. Nonalternans RL precedes ventricular arrhythmia in wider range of conditions than previously appreciated.
Details
- Title: Subtitle
- Accelerated Junctional Rhythm and Nonalternans Repolarization Lability Precede Ventricular Tachycardia in Casq2−/− Mice
- Creators
- URE L MEZU - Heart and Vascular Institute, School of Medicine, University of Pittsburgh, Pennsylvania, USAPRABHPREET SINGH - Department of Medicine, School of Medicine, University of Pittsburgh, Pennsylvania, USAVLADIMIR SHUSTERMAN - Heart and Vascular Institute, School of Medicine, University of Pittsburgh, Pennsylvania, USAHYUN-SEOK HWANG - Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USABJORN C KNOLLMANN - Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USAJAN NĚMEC - Heart and Vascular Institute, School of Medicine, University of Pittsburgh, Pennsylvania, USA
- Resource Type
- Journal article
- Publication Details
- Journal of cardiovascular electrophysiology, Vol.23(12), pp.1355-1363
- Edition
- Manuscript received 25 March 2012; Revised manuscript received 22 May 2012; Accepted for publication 29 May 2012.
- Publisher
- Blackwell Publishing Inc
- DOI
- 10.1111/j.1540-8167.2012.02406.x
- PMID
- 22860618
- ISSN
- 1045-3873
- eISSN
- 1540-8167
- Number of pages
- 9
- Language
- English
- Date published
- 12/2012
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984094326402771
Metrics
26 Record Views