Rosen M R, Miura D S, Danilo P
J Pharmacol Exp Ther. 1975 Apr;193(1):209-17.
The effects of dimethyl quaternary propranolol (UM-272) on electrophysiologic properties of canine cardiac Purkinje fibers (PF) were studied using standard microelectrode techniques. In PF superfused with Tyrode's solution, the effects of UM-272, 10- minus 7 to 10- minus 5 M, were studied. In other experiments, UM-272, 3 mg/kg, was injected into donor animals whose blood was used to superfuse isolated PF. Antiarrhythmic concentrations of UM-272 decreased action potential (AP) amplitude, phase 0 upstroke velocity, membrane responsiveness, AP duration and the effective refractory period (the decrease in the effective refractory period was less than that in AP duration). Automaticity of spontaneously firing PF was suppressed. As perfusate potassium concentration was increased, the magnitude of UM-272 effect was accentuated. When the actions of equimolar concentrations of UM-272 and propranolol on PF AP were compared, propranolol attained a steady-state effect more rapidly and tended to depress the AP more markedly. UM-272 did not block epinephrine-induced increases in PF automaticity or the adenylate cyclase activation of PG homogenates induced by epinephrine. These studies indicate that UM-272 has direct effects on the PF AP similar to those of propranolol, but lacks the beta blocking properties of the latter.
使用标准微电极技术研究了二甲基季铵普萘洛尔（UM - 272）对犬心脏浦肯野纤维（PF）电生理特性的影响。在以台氏液灌流的浦肯野纤维中，研究了浓度为10⁻⁷至10⁻⁵M的UM - 272的作用。在其他实验中，将3mg/kg的UM - 272注射到供体动物体内，然后用其血液灌流分离出的浦肯野纤维。抗心律失常浓度的UM - 272可降低动作电位（AP）幅度、0期去极化速度、膜反应性、AP持续时间和有效不应期（有效不应期的降低小于AP持续时间的降低）。自发放电的浦肯野纤维的自律性受到抑制。随着灌流液钾浓度的增加，UM - 272的作用强度增强。当比较等摩尔浓度的UM - 272和普萘洛尔对浦肯野纤维动作电位的作用时，普萘洛尔达到稳态效应的速度更快，且对动作电位的抑制作用更明显。UM - 272不阻断肾上腺素诱导的浦肯野纤维自律性增加或肾上腺素诱导的PG匀浆腺苷酸环化酶激活。这些研究表明，UM - 272对浦肯野纤维动作电位具有与普萘洛尔相似的直接作用，但缺乏后者的β阻断特性。
