利多卡因、普鲁卡因、普鲁卡因胺和奎尼丁对培养的鸡胚心脏电生理特性的影响。

Effects of lidocaine, procaine, procainamide and quinidine on electrophysiological properties of cultured embryonic chick hearts.

作者信息

Riccioppo Neto F R, Sperelakis N

出版信息

Br J Pharmacol. 1985 Dec;86(4):817-26. doi: 10.1111/j.1476-5381.1985.tb11103.x.

DOI:10.1111/j.1476-5381.1985.tb11103.x

PMID:4075018

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1916628/

Abstract

The effects of lidocaine, procaine, procainamide and quinidine were studied on organ-cultured embryonic chick (2-3 day-old) ventricular cells. Lidocaine (10(-5) - 10(-4)M), in a dose-dependent manner, reduced the rate of pacemaker discharge, the action potential amplitude (APA), the maximum rate of rise (Vmax) of the upstroke of the action potential and the action potential duration at 50% repolarization (APD50). These changes occurred without alterations in the maximum diastolic potential (MDP). Extracellular electrical field stimulation could still evoke action potentials in cells arrested by 10(-4)M lidocaine, but 10(-3)M lidocaine completely abolished electrical activity. Procaine, procainamide and quinidine, at 5 X 10(-5)M to 10(-3)M, depolarized the cells to around -30 mV and reduced APA and Vmax. Procaine and procainamide increased APD50, but quinidine shortened it. All the effects described disappeared completely in about 40 min of superfusion with drug-free Tyrode solution. Isoprenaline (5 X 10(-7)M) and adrenaline (10(-6)M) restored spontaneous firing of preparations arrested by any of the antiarrhythmic agents and repolarized ventricular cells depolarized by procaine, procainamide or quinidine. Propranolol (5 X 10(-7)M) did not affect the depolarization produced by procaine (5 X 10(-4)M), but antagonized its reversal by isoprenaline. In contrast, isoprenaline (10(-6)M) did not produce recovery of automaticity of preparations arrested by verapamil (10(-5)M). Histamine (10(-5)M) or strontium (10 mM) were not able to restore rhythmic activity in cells arrested procaine. Application of long (10-15 s duration) hyperpolarizing currents did not reverse the blocking effect of procaine, procainamide and quinidine. The input resistance increased during the procaine-induced depolarization. It is suggested that the four agents studied block the slow Na+ channels responsible for the upstroke of the action potential in young chick heart cells. A drug-induced decrease in PK may occur in those cells arrested at low levels of membrane potential.

摘要

研究了利多卡因、普鲁卡因、普鲁卡因胺和奎尼丁对器官培养的胚胎鸡（2 - 3日龄）心室细胞的作用。利多卡因（10⁻⁵ - 10⁻⁴M）以剂量依赖方式降低起搏放电速率、动作电位幅度（APA）、动作电位上升支的最大上升速率（Vmax）以及50%复极化时的动作电位持续时间（APD50）。这些变化发生时最大舒张电位（MDP）未改变。细胞外电场刺激仍能在被10⁻⁴M利多卡因阻滞的细胞中诱发动作电位，但10⁻³M利多卡因完全消除电活动。5×10⁻⁵M至10⁻³M的普鲁卡因、普鲁卡因胺和奎尼丁使细胞去极化至约 - 30 mV，并降低APA和Vmax。普鲁卡因和普鲁卡因胺增加APD50，但奎尼丁使其缩短。用无药的台氏液灌注约40分钟后，上述所有作用完全消失。异丙肾上腺素（5×10⁻⁷M）和肾上腺素（10⁻⁶M）可恢复被任何一种抗心律失常药物阻滞的标本的自发放电，并使被普鲁卡因、普鲁卡因胺或奎尼丁去极化的心室细胞复极化。普萘洛尔（5×10⁻⁷M）不影响由5×10⁻⁴M普鲁卡因产生的去极化，但拮抗异丙肾上腺素对其的逆转作用。相比之下，异丙肾上腺素（10⁻⁶M）不能使被维拉帕米（10⁻⁵M）阻滞的标本恢复自动节律性。组胺（10⁻⁵M）或锶（10 mM）不能恢复被普鲁卡因阻滞的细胞的节律性活动。施加长时间（持续10 - 15秒）的超极化电流不能逆转普鲁卡因、普鲁卡因胺和奎尼丁的阻滞作用。在普鲁卡因诱导的去极化过程中输入电阻增加。提示所研究的这四种药物阻滞了负责幼雏心脏细胞动作电位上升支的慢钠通道。在膜电位处于低水平而被阻滞的细胞中可能会发生药物诱导的PK降低。