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Ventricular repolarization time, location of pacing stimulus and current pulse amplitude conspire to determine arrhythmogenicity in mice
Author(s) -
Speerschneider T.,
Grubb S.,
Olesen S. P.,
Calloe K.,
Thomsen M. B.
Publication year - 2017
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12761
Subject(s) - repolarization , proarrhythmia , medicine , cardiology , ventricular repolarization , ventricle , refractory period , atrial action potential , ventricular action potential , electrophysiology , qt interval , endocrinology
Aim In this study, we investigate the impact of altered action potential durations ( APD ) on ventricular repolarization time and proarrhythmia in mice with and without genetic deletion of the K + ‐channel‐interacting protein 2 ( KC h IP 2 −/− and WT respectively). Moreover, we examine the interrelationship between the dispersion of repolarization time and current pulse amplitude in provoking ventricular arrhythmia. Methods Intracardiac pacing in anesthetized mice determined refractory periods and proarrhythmia susceptibility. Regional activation time ( AT ), APD and repolarization time (= AT + APD ) were measured in isolated hearts using floating microelectrodes. Results Proarrhythmia in WT and KC h IP 2 −/− was not sensitive to changes in refractory periods. Action potentials were longer in KC h IP 2 −/− hearts compared to WT hearts. Isolated WT hearts had large apico‐basal dispersion of repolarization time, whereas hearts from KC h IP 2 −/− mice had large left‐to‐right ventricular dispersion of repolarization time. Pacing from the right ventricle in KC h IP 2 −/− mice in vivo revealed significant lower current pulse amplitudes needed to induce arrhythmias in these mice. Conclusion Large heterogeneity of repolarization time is proarrhythmic when pacing is delivered from the location of earlier repolarization time. Ventricular repolarization time, location of the pacing stimulus and the amplitude of the stimulating current pulse are critical parameters underlying arrhythmia vulnerability.