Wyse K R, Ye V, Campbell T J
Department of Clinical Pharmacology, St. Vincent's Hospital, Darlinghurst, NSW, Sydney, Australia.
Br J Pharmacol. 1993 Jan;108(1):255-61. doi: 10.1111/j.1476-5381.1993.tb13471.x.
1 Standard microelectrode methods were used to record intracellular action potentials from strips of guinea-pig right ventricular myocardium superfused with either standard physiological saline ([K+] = 5.6 mM) or the same solution modified to contain [K+] = 11.2 mM. 2 The effects on action potential parameters of three therapeutic concentrations of mexiletine, quinidine and disopyramide were studied under both conditions at four different drive rates (interstimulus intervals = 2400, 1200, 600 and 300 ms). 3 Hyperkalaemia in the absence of drugs produced reductions in resting potential (-86.7 +/- 2.5 mV to -71.8 +/- 3.7 mV; n = 30; P < 0.001), maximum rate of depolarization (300 +/- 46.5 V s-1 to 205.6 +/- 37.6 V s-1; P < 0.0001), and action potential duration (205 +/- 26 ms to 188 +/- 32 ms; P < 0.05). 4 All three drugs produced increased depression of maximum rate of depolarization in hyperkalaemia compared to control conditions, but at all three concentrations this enhancement of effect was greater for mexiletine than for quinidine, with disopyramide exhibiting intermediate behaviour. 5 Mexiletine behaved very similarly to therapeutic concentrations of lignocaine as described in previous reports from this laboratory. 6 Quinidine behaved very similarly to Class Ic agents. 7 It is concluded that mexiletine demonstrated significantly greater selectivity for depolarized myocardium than quinidine and that this may have implications in terms of proarrhythmic potential. 8 Disopyramide exhibited intermediate selectivity for depolarized myocardium between mexiletine and quinidine.
采用标准微电极方法，记录豚鼠右心室心肌条带的细胞内动作电位，该心肌条带分别用标准生理盐水（[K⁺]=5.6 mM）或经改良使其含有[K⁺]=11.2 mM的相同溶液进行灌流。
在两种条件下，于四种不同的驱动频率（刺激间隔=2400、1200、600和300毫秒）下，研究了三种治疗浓度的美西律、奎尼丁和丙吡胺对动作电位参数的影响。
在无药物情况下，高钾血症使静息电位降低（从-86.7±2.5 mV降至-71.8±3.7 mV；n = 30；P<0.001），最大去极化速率降低（从300±46.5 V s⁻¹降至205.6±37.6 V s⁻¹；P<0.0001），动作电位时程缩短（从205±26毫秒降至188±32毫秒；P<0.05）。
与对照条件相比，所有三种药物在高钾血症时均使最大去极化速率的抑制作用增强，但在所有三种浓度下，美西律的这种效应增强程度均大于奎尼丁，丙吡胺表现出中间行为。
美西律的行为与本实验室先前报道的治疗浓度的利多卡因非常相似。
奎尼丁的行为与Ic类药物非常相似。
结论是，美西律对去极化心肌的选择性明显高于奎尼丁，这可能在促心律失常潜能方面具有影响。
丙吡胺对去极化心肌的选择性介于美西律和奎尼丁之间。
