Cerbai E, De Bonfioli Cavalcabó P, Masini I, Porciatti F, Mugelli A
Department of Preclinical and Clinical Pharmacology, University of Firenze, Italy.
Eur J Pharmacol. 1989 Mar 29;162(3):491-500. doi: 10.1016/0014-2999(89)90340-3.
Recent data suggest that the opioid antagonist naloxone may exert an antiarrhythmic action on arrhythmias caused by coronary artery occlusion and reperfusion in experimental animals. We used intracellular microelectrodes to study the direct electrophysiological properties of naloxone. Experiments were carried out on sheep cardiac Purkinje fibers, the electrical and mechanical activity of which were recorded simultaneously. Naloxone (10(-7)-10(-4) M) caused a prolongation of the action potential duration, a decrease in the maximum rate of depolarization, a flattening of the slope of diastolic depolarization and a decrease in contractility. Naloxone at 10(-6) M significantly reduced the rate of spontaneously beating Purkinje fibers and at 10(-5) M completely blocked normal automaticity. Naloxone had, however, intriguing effect on the oscillatory afterpotentials, which is a relevant arrhythmogenic mechanism. While naloxone (10(-7)-10(-4) M) did not affect the digitalis-induced oscillatory afterpotentials, it increased the amplitude of the barium-induced oscillatory afterpotentials at lower concentrations (10(-7) M) and decreased the amplitude of these potentials at high concentrations (10(-6)-10(-4) M). It is concluded that naloxone exerts a direct electrophysiological effect on cardiac cells and that this effect is probably important for explaining the antiarrhythmic action of naloxone.
最近的数据表明，阿片类拮抗剂纳洛酮可能对实验动物冠状动脉阻塞和再灌注引起的心律失常发挥抗心律失常作用。我们使用细胞内微电极研究纳洛酮的直接电生理特性。实验在绵羊心脏浦肯野纤维上进行，同时记录其电活动和机械活动。纳洛酮（10^(-7)-10^(-4)M）导致动作电位时程延长、最大去极化速率降低、舒张期去极化斜率变平以及收缩力下降。10^(-6)M的纳洛酮显著降低了自发搏动的浦肯野纤维的速率，而10^(-5)M时则完全阻断了正常自律性。然而，纳洛酮对振荡后电位有有趣的影响，这是一种相关的致心律失常机制。虽然纳洛酮（10^(-7)-10^(-4)M）不影响洋地黄诱导的振荡后电位，但在较低浓度（10^(-7)M）时增加了钡诱导的振荡后电位的幅度，而在高浓度（10^(-6)-10^(-4)M）时降低了这些电位的幅度。得出的结论是，纳洛酮对心脏细胞发挥直接电生理作用，并且这种作用可能对于解释纳洛酮的抗心律失常作用很重要。
