The Complex QT/RR Relationship in Mice.

Julien Roussel,Jean-Yves Le Guennec,Jérôme Roy,Jérôme Thireau,Sylvain Richard,Jérémy Fauconnier,Pascal Champeroux

doi:10.1038/srep25388

Abstract

The QT interval reflects the time between the depolarization of ventricles until their repolarization and is usually used as a predictive marker for the occurrence of arrhythmias. This parameter varies with the heart rate, expressed as the RR interval (time between two successive ventricular depolarizations). To calculate the QT independently of the RR, correction formulae are currently used. In mice, the QT-RR relationship as such has never been studied in conscious animals, and correction formulas are mainly empirical. In the present paper we studied how QT varies when the RR changes physiologically (comparison of nocturnal and diurnal periods) or after dosing mice with tachycardic agents (norepinephrine or nitroprusside). Our results show that there is significant variability of QT and RR in a given condition, resulting in the need to average at least 200 consecutive complexes to accurately compare the QT. Even following this method, no obvious shortening of the QT was observed with increased heart rate, regardless of whether or not this change occurs abruptly. In conclusion, the relationship between QT and RR in mice is weak, which renders the use of correction formulae inappropriate and misleading in this species.

Highlights

The QT interval reflects the time between the depolarization of ventricles until their repolarization and is usually used as a predictive marker for the occurrence of arrhythmias
It has been shown that the QT interval, representing the duration of the ventricular depolarization of the action potential (AP), depends on the heart rate (HR)
This is known as the QT-RR relationship, the RR interval being the period between two consecutive ventricular depolarizations

Summary

Introduction

The QT interval reflects the time between the depolarization of ventricles until their repolarization and is usually used as a predictive marker for the occurrence of arrhythmias. In humans, an increase in pacing rate can accumulate IKS in the open state and activate the Ca2+ dependent Cl- current (ITO2), resulting in a shortening of the action potential duration (APD)[5,6,7,8] These electrophysiological determinants of the frequency-dependence of the APD differ between species. Bazett[12] and Fridericia[13], by analyzing a large number of ECGs, have empirically developed correction formulae that are the most used in humans These formulas have subsequently been applied in animals, but it has been observed that the corrected QT (QTc) is overestimated at high HRs and underestimated at low HRs14. This approach, dedicated to pharmacological safety www.nature.com/scientificreports/

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Conclusion