LIDOCAINES NEGATIVE INOTROPIC AND ANTIARRHYTHMIC ACTIONS - DEPENDENCE ON SHORTENING OF ACTION-POTENTIAL DURATION AND REDUCTION OF INTRACELLULAR SODIUM ACTIVITY
LIDOCAINES NEGATIVE INOTROPIC AND ANTIARRHYTHMIC ACTIONS - DEPENDENCE ON SHORTENING OF ACTION-POTENTIAL DURATION AND REDUCTION OF INTRACELLULAR SODIUM ACTIVITY
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DOI：
10.1161/01.res.57.4.578
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发表时间：
1985-01-01
影响因子：
20.1
通讯作者：
LEDERER, WJ
中科院分区：
文献类型：
--
作者：
SHEU, SS;LEDERER, WJ
利多卡因在心脏中产生负性肌力作用和抗心律失常作用的机制已被研究。使用绵羊心脏浦肯野纤维，我们研究了“治疗”浓度的利多卡因（20 μ M利多卡因= 5.4 μ g/ml）对电活动、细胞内钠活动和张力的影响。对于具有正常生理水平的细胞内钠活性（5-9 mM）的制剂，利多卡因的应用导致以下作用：（1）动作电位持续时间缩短，（2）细胞内钠活性福尔斯下降，和（3）抽搐张力降低。如果细胞内钠活性首先升高（例如，通过钠泵抑制），从而使致心律失常的瞬时去极化（和潜在的瞬时内向电流可见），那么利多卡因具有以下作用：（1）动作电位时程缩短。(2)伴随短暂去极化（或短暂内向电流）减少的后收缩的致心律失常瞬变幅度减少。(4)如果在钠泵抑制后，细胞内钠活性仍在上升，那么利多卡因的应用会导致细胞内钠的上升速率降低。从这些结果，平行的电压钳实验，和最近的工作，由其他人，我们得出结论，利多卡因导致心律失常的短暂去极化和减少收缩张力的减少，通过减少内向钠电流。这些作用是通过动作电位持续时间的缩短以及细胞内钠活性和细胞内钙活性的降低（通过钠-钙交换机制）介导的。
The mechanisms by which lidocaine brings about negative inotropic effects and antiarrhythmic actions in the heart have been examined. Using sheep cardiac Purkinje fibers, we studied the effects of "therapeutic" concentrations of lidocaine (20 .mu.M lidocaine = 5.4 .mu.g/ml) on electrical activity, intracellular sodium activity, and tension. For the preparation with a normal, physiological level of intracellular sodium activity (5-9 mM), the application of lidocaine leads to the following actions: (1) action potential duration is decreased, (2) intracellular sodium activity falls, and (3) twitch tension is reduced. If intracellular sodium activity is first elevated (e.g., by sodium pump inhibition) so that arrhythmogenic transient depolarizations (and the underlying transient inward current are seen) then lidocaine has the following actions: (1) The action potential duration is reduced. (2) There is a reduction of the magnitude of the arrhythmogenic transient of the after contraction that accompanies the transient depolarization (or transient inward current) is reduced. (4) If, after sodium pump inhibition, intracellular sodium activity is still rising.sbd.then, the application of lidocaine leads to a reduction of the rate of rise of intracellular sodium. From these results, parallel voltage-clamp experiments, and recent work by others, we conclude that lidocaine leads to the reduction of the arrhytymogenic transient depolarization and a reduction of twitch tension by decreasing the inward sodium current. These actions are mediated by a reduction in action potential duration and a reduction of intracellular sodium activity and of intracellular calcium activity (by the sodium-calcium exchange mechanism).