HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 15/1/84    most recent 00034.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (17) Citing Articles via Google Scholar Google Scholar Articles by Maguire, C. T. Articles by Berul, C. I. Search for Related Content PubMed PubMed Citation Articles by Maguire, C. T. Articles by Berul, C. I.

Toolbox

Implications of ventricular arrhythmia vulnerability during murine electrophysiology studies

¹ Department of Cardiology, Children’s Hospital, Boston and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115
² Molecular Cardiology Research Center and Section of Cardiac Electrophysiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Programmed ventricular stimulation is being performed for the provocation of ventricular arrhythmias in genetically engineered mice. Despite the high level of interest in this area of translational research, little attention has been given to differentiating between selectivity and specificity of induced ventricular tachycardia (VT) in phenotypically normal mice. We aimed to assess factors that may enhance inducibility of VT in wild-type (WT) mice. In vivo intracardiac electrophysiological studies (EPS) were performed in 230 WT mice of 4 strains. An octapolar electrode catheter was inserted into a jugular vein and advanced to the right atrium and ventricle. Baseline ventricular conduction, refractoriness, and arrhythmia inducibility were assessed using programmed electrical stimulation (PES) and burst pacing. We found that nonsustained VT (4 beats) was inducible in 68/230 (30%) mice. Duration of VT was 1.6 ± 2.4 s, and the longest episode lasted 24 s. VT inducibility differed by strain and age. Ventricular effective refractory period (VERP) was shorter in mice with inducible VT (44 ± 12 ms) compared with noninducible mice (61 ± 16 ms, P < 0.001). VERP increased with age (P < 0.001), albeit with strain-related variability. We conclude that nonsustained VT in WT mice is reproducibly inducible and common. Genetic background variability may predispose certain strains to a higher incidence of arrhythmia induction. EPS methods impact prevalence and specificity of inducible VT. Increased VT inducibility was seen with shorter coupling intervals and application of tightly coupled extrastimuli techniques. These factors should be carefully considered when analyzing PES and burst pacing data in murine models to minimize false positives and optimize accuracy.

mice; ventricular tachycardia; programmed stimulation; genetics

This article has been cited by other articles:

				J. Qu, F. M. Volpicelli, L. I. Garcia, N. Sandeep, J. Zhang, L. Marquez-Rosado, P. D. Lampe, and G. I. Fishman Gap Junction Remodeling and Spironolactone-Dependent Reverse Remodeling in the Hypertrophied Heart Circ. Res., February 13, 2009; 104(3): 365 - 371. [Abstract] [Full Text] [PDF]

				B. Gellen, M. Fernandez-Velasco, F. Briec, L. Vinet, K. LeQuang, P. Rouet-Benzineb, J.-P. Benitah, M. Pezet, G. Palais, N. Pellegrin, et al. Conditional FKBP12.6 Overexpression in Mouse Cardiac Myocytes Prevents Triggered Ventricular Tachycardia Through Specific Alterations in Excitation- Contraction Coupling Circulation, April 8, 2008; 117(14): 1778 - 1786. [Abstract] [Full Text] [PDF]

				G. Thomas, M. J. Killeen, I. S. Gurung, P. Hakim, R. Balasubramaniam, C. A. Goddard, A. A. Grace, and C. L.-H. Huang Mechanisms of ventricular arrhythmogenesis in mice following targeted disruption of KCNE1 modelling long QT syndrome 5 J. Physiol., January 1, 2007; 578(1): 99 - 114. [Abstract] [Full Text] [PDF]

				G. Thomas, I. S. Gurung, M. J. Killeen, P. Hakim, C. A. Goddard, M. P. Mahaut-Smith, W. H. Colledge, A. A. Grace, and C. L.-H. Huang Effects of L-type Ca2+ channel antagonism on ventricular arrhythmogenesis in murine hearts containing a modification in the Scn5a gene modelling human long QT syndrome 3 J. Physiol., January 1, 2007; 578(1): 85 - 97. [Abstract] [Full Text] [PDF]

				T. Betsuyaku, N. S. Nnebe, R. Sundset, S. Patibandla, C. M. Krueger, and K. A. Yamada Overexpression of cardiac connexin45 increases susceptibility to ventricular tachyarrhythmias in vivo Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H163 - H171. [Abstract] [Full Text] [PDF]

				C. M. Wolf, I. P. G. Moskowitz, S. Arno, D. M. Branco, C. Semsarian, S. A. Bernstein, M. Peterson, M. Maida, G. E. Morley, G. Fishman, et al. Somatic events modify hypertrophic cardiomyopathy pathology and link hypertrophy to arrhythmia PNAS, December 13, 2005; 102(50): 18123 - 18128. [Abstract] [Full Text] [PDF]

				S. Demolombe, C. Marionneau, S. Le Bouter, F. Charpentier, and D. Escande Functional genomics of cardiac ion channel genes Cardiovasc Res, August 15, 2005; 67(3): 438 - 447. [Abstract] [Full Text] [PDF]

				L. C. Mounkes, S. V. Kozlov, J. N. Rottman, and C. L. Stewart Expression of an LMNA-N195K variant of A-type lamins results in cardiac conduction defects and death in mice Hum. Mol. Genet., August 1, 2005; 14(15): 2167 - 2180. [Abstract] [Full Text] [PDF]

				S. B. Danik, F. Liu, J. Zhang, H. J. Suk, G. E. Morley, G. I. Fishman, and D. E. Gutstein Modulation of Cardiac Gap Junction Expression and Arrhythmic Susceptibility Circ. Res., November 12, 2004; 95(10): 1035 - 1041. [Abstract] [Full Text] [PDF]

				S. Brunet, F. Aimond, H. Li, W. Guo, J. Eldstrom, D. Fedida, K. A. Yamada, and J. M. Nerbonne Heterogeneous expression of repolarizing, voltage-gated K+ currents in adult mouse ventricles J. Physiol., August 15, 2004; 559(1): 103 - 120. [Abstract] [Full Text] [PDF]