Berman N D, Wang L Y, Ogilvie R I
Division of Cardiology, Toronto Western Hospital, Ontario.
Can J Cardiol. 1992 Jan-Feb;8(1):69-77.
The combination of mexiletine and amiodarone has proved useful in the control of serious ventricular arrhythmias, but the electrophysiological basis for their effectiveness in combination is unknown. The objective of this study was to compare the effects of mexiletine on action potential parameters of papillary muscles taken from guinea pigs chronically treated with amiodarone, with tissue taken from a control group.
The effects of 12.5 to 200 microM mexiletine on action potential parameters of papillary muscles taken from guinea pigs chronically treated with amiodarone were compared with tissue taken from a control group, at frequencies of 1.0, 1.5 and 3.0 Hz, using standard microelectrode techniques. Onset of use-dependent block was assessed by 30 beat trains, and recovery from block by extrastimuli at diastolic intervals ranging from 200 to 5000 ms at both 1.5 and 3.0 Hz.
Eighteen four-week-old guinea pigs were randomly divided into two groups. One group received amiodarone in a loading dose of 20 mg/kg/day by intraperitoneal injection for one week, followed by 10 mg/kg/day for 15 weeks. The control animals were given equivalent volumes of dextrose intraperitoneally for 16 weeks.
Mexiletine depressed the maximum rate of depolarization of phase 0 of the action potential (Vmax) in a concentration- and use-dependent fashion. Whereas chronic amiodarone treatment did not alter steady-state Vmax values, the extent of tonic Vmax depression induced by mexiletine was decreased, while use-dependent depression was increased. Mexiletine combined with amiodarone increased effective refractory period prolongation from 306.7 +/- 27.2 to 348.8 +/- 37.2 ms, while action potential duration shortening of mexiletine was moderated from 134.0 +/- 19.8 to 151.0 +/- 8.3 ms (to 90% repolarization at 3 Hz in the presence of 200 microM mexiletine).
美西律与胺碘酮联合使用已被证明对控制严重室性心律失常有效，但其联合使用有效性的电生理基础尚不清楚。本研究的目的是比较美西律对长期接受胺碘酮治疗的豚鼠乳头肌动作电位参数的影响，并与对照组的组织进行比较。
采用标准微电极技术，比较12.5至200微摩尔美西律对长期接受胺碘酮治疗的豚鼠乳头肌动作电位参数的影响，并与对照组的组织进行比较，频率分别为1.0、1.5和3.0赫兹。通过30次搏动序列评估使用依赖性阻滞的起始情况，并通过在1.5和3.0赫兹下舒张期间隔为200至5000毫秒的额外刺激评估阻滞的恢复情况。
将18只四周龄豚鼠随机分为两组。一组通过腹腔注射给予负荷剂量为20毫克/千克/天的胺碘酮，持续一周，随后给予10毫克/千克/天，持续15周。对照组动物腹腔注射等量葡萄糖，持续16周。
美西律以浓度和使用依赖性方式降低动作电位0期的最大去极化速率（Vmax）。虽然长期胺碘酮治疗未改变稳态Vmax值，但美西律诱导的强直性Vmax降低程度减小，而使用依赖性降低增加。美西律与胺碘酮联合使用使有效不应期延长从306.7±27.2毫秒增加到348.8±37.2毫秒，而美西律引起的动作电位时程缩短从134.0±19.8毫秒减轻到151.0±8.3毫秒（在存在200微摩尔美西律的情况下，在3赫兹时复极化至90%）。
