Published Online
on July 1, 2002

A more recent version of this article appeared on July 23, 2002

This Article Full Text (PDF) All Versions of this Article: 106/4/497    most recent 01.CIR.0000023629.72479.24v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Drici, M.-D. Articles by Salama, G. Search for Related Content PubMed Articles by Drici, M.-D. Articles by Salama, G. Related Collections Arrythmias-basic studies

Submitted on February 22, 2002
Revised on April 30, 2002
Accepted on May 1, 2002

Mice Display Sex Differences in Halothane-Induced Polymorphic Ventricular Tachycardia

Milou-Daniel Drici MD, PhD, Linda Baker PhD, Patricia Plan , Jacques Barhanin PhD, Georges Romey PhD, and Guy Salama PhD^*

From Centre National de la Recherche Scientifique-Unité Mixte de Recherche, Sophia Antipolis, 06560 Valbonne, France, and Department of Cell Biology and Physiology (L.B., P.P., G.S.), University of Pittsburgh, Pa.

^* To whom correspondence should be addressed. E-mail: gsalama{at}pitt.edu.

Background—Molecularly engineered mice are extensively used as models of cardiovascular diseases, yet little is known about sex differences in the electrophysiology of mouse hearts.

Methods and Results—This study investigated the influence of sex on drug-induced polymorphic ventricular tachycardia (PVT) in Langendorff-perfused male and female mice hearts (n=54) by injecting a bolus of halothane (1.75 mmol/L) in the perfusate while recording ECGs or optical action potentials (APs). There were no statistically significant differences between male and female hearts (n=54) with respect to mean RR (193±5 ms), PR (47±1 ms), QT intervals (101±3 ms), optical AP durations (APD₇₅=23.11±4.2 ms), dispersion of refractory periods, and conduction velocities (n=5 male and 5 female). Halothane induced PVTs lasting a mean duration of 90 seconds; in female hearts, 55% of PVTs lasted longer than the median, whereas in male hearts 17% exceeded the mean (P<0.05). The total duration of PVTs exposed a marked sex difference, 378±144 seconds in female versus 27±10 seconds in male hearts (P<0.05). In optically mapped male hearts, halothane reduced APD₇₅ (17.61±1.6 ms) and then elicited VTs (n=6 of 6), but in female hearts, halothane elicited PVTs (n=1 of 6) or arrested the hearts (n=5 of 6). Except for KCNE1, Northern blots (KCNQ1, MERG, Kv1.5, connexins 40 and 43, TREK1, and TASK1) did not detect sex differences.

Conclusions—This mouse model reveals sex difference in response to a pharmacological challenge yet does not display sex differences in standard electrophysiological parameters. Differences in KCNE1 may contribute to sex differences uncovered by halothane.

Key words: action potentials • tachycardia • sex • electrophysiology • mapping

This article has been cited by other articles:

				G. Salama and B. London Mouse models of long QT syndrome J. Physiol., January 1, 2007; 578(1): 43 - 53. [Abstract] [Full Text] [PDF]

				B. London, L. C. Baker, P. Petkova-Kirova, J. M. Nerbonne, B.-R. Choi, and G. Salama Dispersion of repolarization and refractoriness are determinants of arrhythmia phenotype in transgenic mice with long QT J. Physiol., January 1, 2007; 578(1): 115 - 129. [Abstract] [Full Text] [PDF]

				T. Korte, M. Fuchs, A. Arkudas, S. Geertz, R. Meyer, A. Gardiwal, G. Klein, M. Niehaus, A. Krust, P. Chambon, et al. Female Mice Lacking Estrogen Receptor {beta} Display Prolonged Ventricular Repolarization and Reduced Ventricular Automaticity After Myocardial Infarction Circulation, May 10, 2005; 111(18): 2282 - 2290. [Abstract] [Full Text] [PDF]

				J. Brouillette, K. Rivard, E. Lizotte, and C. Fiset Sex and strain differences in adult mouse cardiac repolarization: importance of androgens Cardiovasc Res, January 1, 2005; 65(1): 148 - 157. [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]

				C. T. Maguire, H. Wakimoto, V. V. Patel, P. E. Hammer, K. Gauvreau, and C. I. Berul Implications of ventricular arrhythmia vulnerability during murine electrophysiology studies Physiol Genomics, September 29, 2003; 15(1): 84 - 91. [Abstract] [Full Text] [PDF]