Ventricular repolarization time, location of pacing stimulus and current pulse amplitude conspire to determine arrhythmogenicity in mice
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Ventricular repolarization time, location of pacing stimulus and current pulse amplitude conspire to determine arrhythmogenicity in mice. / Speerschneider, T; Grubb, Søren Jahn; Olesen, S P; Calloe, K; Thomsen, M B.
I: Acta Physiologica, Bind 219, Nr. 3, 09.02.2017, s. 662-670.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › fagfællebedømt
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TY - JOUR
T1 - Ventricular repolarization time, location of pacing stimulus and current pulse amplitude conspire to determine arrhythmogenicity in mice
AU - Speerschneider, T
AU - Grubb, Søren Jahn
AU - Olesen, S P
AU - Calloe, K
AU - Thomsen, M B
N1 - © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
PY - 2017/2/9
Y1 - 2017/2/9
N2 - 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.
AB - 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.
U2 - 10.1111/apha.12761
DO - 10.1111/apha.12761
M3 - Journal article
C2 - 27459728
VL - 219
SP - 662
EP - 670
JO - Acta Physiologica
JF - Acta Physiologica
SN - 1748-1708
IS - 3
ER -
ID: 167474234