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Title of Journal: J Interv Card Electrophysiol

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Abbravation: Journal of Interventional Cardiac Electrophysiology

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Springer US

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DOI

10.1007/bf01263599

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1572-8595

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Arrhythmia phenotype in mouse models of human long

Authors: Guy Salama Linda Baker Robert Wolk Jacques Barhanin Barry London
Publish Date: 2009/01/16
Volume: 24, Issue: 2, Pages: 77-87
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Abstract

Enhanced dispersion of repolarization DR was proposed as a unifying mechanism central to arrhythmia genesis in the long QT LQT syndrome In mammalian hearts K+ channels are heterogeneously expressed across the ventricles resulting in ‘intrinsic’ DR that may worsen in long QT DR was shown to be central to the arrhythmia phenotype of transgenic mice with LQT caused by loss of function of the dominant mouse K+ currents Here we investigated the arrhythmia phenotype of mice with targeted deletions of KCNE1 and KCNH2 genes which encode for minK/IsK and Merg1 mouse homolog of human ERG proteins resulting in loss of function of IKs and IKr respectively Both currents are important human K+ currents associated with LQT5 and LQT2 Loss of minK a protein subunit that interacts with KvLQT1 results in a marked reduction of IKs giving rise to the Jervell and Lange–Nielsen syndrome and the reduced KCNH2 gene reduces MERG and IKrHearts were perfused stained with di4ANEPPS and optically mapped to compare action potential durations APDs and arrhythmia phenotype in homozygous minK minK−/− and heterozygous Merg1 Merg+/− deletions and littermate control mice MinK−/− mice has similar APDs and no arrhythmias n = 4 Merg+/− mice had prolonged APDs from 20 ± 6 to 32 ± 9 ms at the base p 001 from 18 ± 5 to 25 ± 9 ms at the apex p 001 n = 8 longer refractory periods RP 36 ± 14 to 63 ± 27 at the base p 001 and 34 ± 5 to 53 ± 21 ms at the apex p 003 n = 8 higher DR 104 ± 41 vs 14 ± 23 ms p 002 and similar conduction velocities n = 8 Programmed stimulation exposed a higher propensity to VT in Merg+/− mice 60 vs 10 A comparison of mouse models of LQT based on K+ channel mutations important to human and mouse repolarization emphasizes DR as a major determinant of arrhythmia vulnerability


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  1. Adenosine triphosphate-induced atrial fibrillation: the clinical significance and relevance to spontaneous atrial fibrillation
  2. Trends in percutaneous pericardial access during catheter ablation of ventricular arrhythmias: a single-center experience
  3. Comparison between pulsed and continuous radiofrequency delivery
  4. Factors associated with fluoroscopy exposure during pediatric catheter ablation utilizing electroanatomical mapping
  5. Electrophysiologic characteristics of atrial tachycardia originating from the superior vena cava
  6. Clinical evaluation of a new technique to monitor return electrode skin temperature during radiofrequency ablation
  7. Contact force and impedance decrease during ablation depends on catheter location and orientation: insights from pulmonary vein isolation using a contact force-sensing catheter
  8. Long-term monitoring of respiratory rate in patients with heart failure: the Multiparametric Heart Failure Evaluation in Implantable Cardioverter-Defibrillator Patients (MULTITUDE-HF) study
  9. Association between red blood cell distribution width and response to cardiac resynchronization therapy
  10. Modification of atrioventricular conduction in dogs by laser irradiation of Koch’s triangle guided by balloon-tipped cardioscope
  11. Novel SCN5A mutations in two families with “Brugada-like” ST elevation in the inferior leads and conduction disturbances
  12. Clinical criteria for predicting benefit of ICD/PM in post myocardial infarction patients: an AVID and CAST analysis
  13. Characteristics and distribution of complex fractionated atrial electrograms in patients with paroxysmal and persistent atrial fibrillation
  14. Predictors of serious arrhythmic events in patients with nonischemic heart failure
  15. Ablation time efficiency and lesion volume - in vitro comparison of 4 mm, non irrigated, gold- and platinum-iridium-tip radiofrequency ablation catheters
  16. Late thromboembolic events after circumferential pulmonary vein ablation of atrial fibrillation
  17. Fluoroless catheter ablation in adults: a single center experience
  18. Patient care and physician conflicts of interests: the Hydra grows new heads but is any Hercules in sight?
  19. Cardiac calcified amorphous tumor in a patient presenting for ventricular tachycardia ablation: intracardiac echocardiogram diagnosis and management
  20. Atrial fibrillation ablation in patients with gastroesophageal reflux disease or irritable bowel syndrome—the heart to gut connection!
  21. Clinical outcome of left atrial ablation for paroxysmal atrial fibrillation is related to the extent of radiofrequency ablation
  22. Predictors of chronic pulmonary vein reconnections after contact force-guided ablation: importance of completing electrical isolation with circumferential lines and creating sufficient ablation lesion densities
  23. Left atrial posterior wall isolation: the icing on the cake
  24. Catheter ablation of arrhythmic storm triggered by monomorphic ectopic beats in patients with coronary artery disease
  25. Verapamil-sensitive left anterior fascicular ventricular tachycardia associated with a healed myocardial infarction: changes in the delayed Purkinje potential during sinus rhythm

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