title: Early repolarization in mice causes overestimation of ventricular activation time by the QRS duration.
abstract: OBJECTIVE
  Transgenic mice are frequently used to investigate the role of genes involved in cardiac conduction. The QRS duration calculated from the electrocardiogram (ECG) is a commonly used measure for ventricular conduction time. However, the relation between ventricular activation and QRS duration calculated from a mouse surface ECG is not well understood. We aim to relate ventricular activation and repolarization patterns with the mouse ECG.
  
  
  RESULTS
  Ventricular activation and repolarization patterns generated by high-density optical mapping and a six-lead pseudo-ECG were compared in isolated mouse hearts. In addition, mouse ECGs were simulated in silico. Right-ventricular activation ends later than left-ventricular activation. Final activation coincided with the end of the QRS complex in leads III and aVF, but not in leads I, II, aVR, and aVL. The pattern of early repolarization (at 20% of repolarization, RT20) but not of RT50 or RT80 followed the activation pattern. After sodium channel blockade by ajmaline, total ventricular activation time increased by 10.0 ms, whereas QRS duration increased by only 2.1 ms. In mice carrying a mutation in Scn5a (1798insD), ventricular activation ended after the end of the QRS complex (12.9 ± 0.1 vs. 10.8 ± 0.3).
  
  
  CONCLUSIONS
  In the mouse, ventricular myocardium activation and early repolarization waves are simultaneously present. This hampers unequivocal interpretation of the duration of the QRS complex as a measure of ventricular activation duration, especially when conduction is slowed. Under these conditions mapping of local activation and repolarization patterns is required for correct interpretation of the ECG.
authors.affiliation: Department of Anatomy, Embryology, and Physiology, Academic Medical Center Amsterdam, Amsterdam, the Netherlands. b.j.boukens@amc.nl
authors.forename: Bas J
authors.initials: BJ
authors.lastname: Boukens
authors.forename: Mark G
authors.initials: MG
authors.lastname: Hoogendijk
authors.forename: Arie O
authors.initials: AO
authors.lastname: Verkerk
authors.forename: Andre
authors.initials: A
authors.lastname: Linnenbank
authors.forename: Peter
authors.initials: P
authors.lastname: van Dam
authors.forename: Carol-Ann
authors.initials: CA
authors.lastname: Remme
authors.forename: Jan W
authors.initials: JW
authors.lastname: Fiolet
authors.forename: Tobias
authors.initials: T
authors.lastname: Opthof
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Christoffels
authors.forename: Ruben
authors.initials: R
authors.lastname: Coronel
mesh_terms: D000200:Action Potentials; D000818:Animals; D003198:Computer Simulation; D004562:Electrocardiography; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D008955:Models, Cardiovascular; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D026941:Sodium Channel Blockers / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects; D016278:Ventricular Function, Right / Q000187:drug effects; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568321:Scn5a protein, mouse; D026941:Sodium Channel Blockers