Oshikawa N, Watanabe I, Masaki R, Shindo A, Kojima T, Saito S, Ozawa Y, Kanmatsuse K
The Second Department of Internal Medicine, Nihon University School of Medicine, Japan.
J Interv Card Electrophysiol. 2001 Mar;5(1):81-7. doi: 10.1023/a:1009866126492.
Most of the class III antiarrhythmic agents developed in recent years blocks the rapid component of delayed rectifier potassium current (IKr). IKr blocker shows reverse use-dependency and also may cause torsades de pointes at slower heart rate. Ibutilide fumarate, a novel class III antiarrhythmic agent, increases window Na(+) current at the action potential plateau phase. We studied the rate-dependent effect of ibutilide on the electrophysiological parameters of human atrium and ventricle. Franz catheter and a pacing catheter were placed closely in the high right atrium and right ventricular apex to record monophasic action potentials (MAP) during pacing at cycle length (PCL) of 600 ms and 350 ms in eight patients who underwent electrophysiological study. MAP duration of right atrium (RA-MAPD) and right ventricle (RV-MAPD), effective refractory period of RA and RV (RA-ERP and RV-ERP), intra-atrial conduction time (IACT) and intra-ventricular conduction time (IVCT) were measured before and after intravenous administration of ibutilide (0.01 mg/kg up to 1mg). A conduction time from RA pacing spike to distal coronary sinus potential was used to measure IACT, while QRS duration of surface ECG during RV pacing was used to measure IVCT. Ibutilide prolonged RA-MAPD by 60 ms at PCL 600 ms and by 53 ms at PCL 350 ms; RV-MAPD by 48 ms at PCL 600 ms and by 55 ms at PCL 350 ms. Ibutilide did not affected RA and RV-ERP/MAPD ratio, IACT, and IVCT. Ibutilide prolongs MAPD and ERP of human atrium and ventricle without reverse use-dependency.
近年来研发的大多数Ⅲ类抗心律失常药物可阻断延迟整流钾电流（IKr）的快速成分。IKr阻滞剂表现出反向频率依赖性，并且在心率较慢时可能会导致尖端扭转型室速。新型Ⅲ类抗心律失常药物富马酸伊布利特可增加动作电位平台期的窗钠电流。我们研究了伊布利特对人心房和心室电生理参数的频率依赖性作用。在8例接受电生理研究的患者中，将Franz导管和起搏导管紧密放置在高位右心房和右心室心尖处，以便在600 ms和350 ms的周期长度（PCL）起搏期间记录单相动作电位（MAP）。在静脉注射伊布利特（0.01 mg/kg，最大剂量1mg）前后，测量右心房（RA-MAPD）和右心室（RV-MAPD）的MAP持续时间、RA和RV的有效不应期（RA-ERP和RV-ERP）、心房内传导时间（IACT）和心室内传导时间（IVCT）。从RA起搏尖峰到远端冠状窦电位的传导时间用于测量IACT，而RV起搏期间体表心电图的QRS持续时间用于测量IVCT。在PCL为600 ms时，伊布利特使RA-MAPD延长60 ms，在PCL为350 ms时延长53 ms；在PCL为600 ms时，使RV-MAPD延长48 ms，在PCL为350 ms时延长55 ms。伊布利特不影响RA和RV-ERP/MAPD比值、IACT和IVCT。伊布利特可延长人心房和心室的MAPD和ERP，且无反向频率依赖性。
