Ventricular repolarization time, location of pacing stimulus and current pulse amplitude conspire to determine arrhythmogenicity in mice.

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 (KChIP2 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 KChIP2 was not sensitive to changes in refractory periods. Action potentials were longer in KChIP2 hearts compared to WT hearts. Isolated WT hearts had large apico-basal dispersion of repolarization time, whereas hearts from KChIP2 mice had large left-to-right ventricular dispersion of repolarization time. Pacing from the right ventricle in KChIP2 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.