Hiraoka I, Oshita S, Morimoto Y, Ban T
Department of Anesthesiology-Resuscitology, School of Medicine, Yamaguchi University, Ube.
Masui. 1990 Feb;39(2):196-203.
Effects of lidocaine 5, 10, 20 micrograms.ml-1 and its metabolite, MEGX 5, 10, 20 micrograms.ml-1, on transmembrane action potentials were studied in isolated guinea-pig papillary muscles, perfused with modified Tyrode's solution. The basic driving rate was 1 Hz and the rate was changed from 1 Hz to 0.25, 0.5, 2, 3 and 4 Hz in a stepwise manner. Both lidocaine and MEGX produced dose- and rate-dependent depression of maximum rate of rise of action potential (Vmax) without significant changes in resting membrane potentials. The recovery kinetics of Vmax was studied by either applying premature stimuli at basic driving rate of 0.25 Hz or by stopping the basic driving of 1 Hz for 1s to 60s. A slow component (time constant: 176-206 ms for lidocaine, 300-340 ms for MEGX) was observed in premature response. And a slower component (time constant: 3-4s for MEGX) was observed in the first response after stopping stimulation. Both drugs shortened the action potential duration. These results suggest that MEGX has a lidocaine-like class I antiarrhythmic actions and that it might modify the actions of lidocaine especially in patients with elevated plasma MEGX concentration.
在灌注改良台氏液的豚鼠离体乳头肌上,研究了5、10、20微克/毫升的利多卡因及其代谢产物5、10、20微克/毫升的MEGX对跨膜动作电位的影响。基础驱动频率为1赫兹,并以逐步方式将频率从1赫兹改变为0.25、0.5、2、3和4赫兹。利多卡因和MEGX均产生剂量和频率依赖性的动作电位最大上升速率(Vmax)抑制,而静息膜电位无显著变化。通过在0.25赫兹的基础驱动频率下施加过早刺激或通过将1赫兹的基础驱动停止1秒至60秒来研究Vmax的恢复动力学。在过早反应中观察到一个缓慢成分(时间常数:利多卡因176 - 206毫秒,MEGX 300 - 340毫秒)。在停止刺激后的首次反应中观察到一个更慢的成分(时间常数:MEGX为3 - 4秒)。两种药物均缩短了动作电位持续时间。这些结果表明,MEGX具有类似利多卡因的I类抗心律失常作用,并且它可能会改变利多卡因的作用,尤其是在血浆MEGX浓度升高的患者中。