Accelerated Junctional Rhythm and Nonalternans Repolarization Lability Precede Ventricular Tachycardia in Casq2−/− Mice...Calsequestrin-2

Repolarization Lability in Casq2−/− Mice. Background: Calsequestrin-2 (CASQ2) is a Ca2+ 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. Repo...

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Publicado en:Journal of Cardiovascular Electrophysiology Vol. 23; no. 12; pp. 1355 - 1364
Autores principales: MEZU, URE L., SINGH, PRABHPREET, SHUSTERMAN, VLADIMIR, HWANG, HYUN‐SEOK, KNOLLMANN, BJORN C., NĚMEC, JAN
Formato: equations & formulas research tables/charts tracings Journal Article
Publicado: Wiley-Blackwell Dec2012
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Dec2012
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1111/j.1540-8167.2012.02406.x
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        atl: Accelerated Junctional Rhythm and Nonalternans Repolarization Lability Precede Ventricular Tachycardia in Casq2−/− Mice...Calsequestrin-2
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          MEZU, URE L.
          SINGH, PRABHPREET
          SHUSTERMAN, VLADIMIR
          HWANG, HYUN‐SEOK
          KNOLLMANN, BJORN C.
          NĚMEC, JAN
        affil: Heart and Vascular Institute, School of Medicine, University of Pittsburgh, Pennsylvania, USA
      sug:
        subj:
          Tachycardia, Ventricular Pathology
          Tachycardia, Ventricular Familial and Genetic
          Electrocardiography
          Calcium Binding Proteins
          Mutation
          Animal Studies
          Mice
          Heart Rate
          Descriptive Statistics
          Isoproterenol Administration and Dosage
          Fisher's Exact Test
          T-Tests
          Heart Conduction System Pathology
          Funding Source
          Data Analysis Software
      ab: Repolarization Lability in Casq2−/− Mice. Background: Calsequestrin-2 (CASQ2) is a Ca2+ 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. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1355-1363, December 2012)
      pubtype: Academic Journal
      doctype:
        equations & formulas
        research
        tables/charts
        tracings
        Journal Article
      ougenre: Article
    language: English
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