Speerschneider T, Grubb S, Olesen S P, Calloe K, Thomsen M B
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Veterinary Clinical and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Acta Physiol (Oxf). 2017 Mar;219(3):660-668. doi: 10.1111/apha.12761. Epub 2016 Aug 24.
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.
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.
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.
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.
在本研究中，我们调查了动作电位时程（APD）改变对野生型（WT）和基因敲除K通道相互作用蛋白2（KChIP2）的小鼠心室复极时间和致心律失常作用的影响。此外，我们研究了复极时间离散度与诱发室性心律失常的电流脉冲幅度之间的相互关系。
通过对麻醉小鼠进行心内起搏来确定不应期和致心律失常易感性。使用浮动微电极在离体心脏中测量局部激动时间（AT）、APD和复极时间（=AT + APD）。
WT和KChIP2小鼠的致心律失常作用对不应期变化不敏感。与WT心脏相比，KChIP2心脏的动作电位更长。离体WT心脏的复极时间在心底-心尖方向存在较大离散度，而KChIP2小鼠心脏的复极时间在左-右心室方向存在较大离散度。对KChIP2小鼠进行体内右心室起搏时发现，诱发这些小鼠心律失常所需的电流脉冲幅度明显更低。
当起搏从复极时间较早的部位进行时，复极时间的大异质性具有致心律失常作用。心室复极时间、起搏刺激部位和刺激电流脉冲幅度是心律失常易感性的关键参数。
