Tande P M, Refsum H
Department of Physiology, University of Tromsø, Norway.
Pharmacol Toxicol. 1990 Jan;66(1):18-22. doi: 10.1111/j.1600-0773.1990.tb00694.x.
Negative inotropy is an adverse feature of most antiarrhythmic drugs. Positive inotropy, however, has been demonstrated for some drugs with class III antiarrhythmic action. Although amiodarone exerts its antiarrhythmic effect by an interplay of different actions on cardiac cells, it has been regarded to be the prototype class III drug due to its prolongation of action potential duration. The present study was designed to test the hypothesis that class III antiarrhythmic action and positive inotropy may be linked. We compared the effects of amiodarone in Cordarone and its solvent Tween 80 on automaticity, refractoriness and inotropy. Two series of experiments were done; one with spontaneously beating rat atria to study the effects on sinus node function, and one with electrically stimulated left atria to study the effects on excitability, refractoriness and inotropy. Amiodarone 1 x 10(-4) M decreased spontaneous heart rate by 13% and prolonged sinus node recovery time by 105%. Without affecting the excitability amiodarone prolonged the effective refractory period by 12%. At the same time contractile force increased by 12%. Lower concentration of amiodarone (5 x 10(-6) M) or Tween 80 had no significant effects. In conclusion, amiodarone exerts acute electrophysiological and inotropic effects in vitro. The class III antiarrhythmic action of amiodarone is linked with positive inotropy.
负性肌力作用是大多数抗心律失常药物的一个不良特性。然而，一些具有Ⅲ类抗心律失常作用的药物已被证明具有正性肌力作用。尽管胺碘酮通过对心肌细胞的不同作用相互影响来发挥其抗心律失常作用，但由于其延长动作电位时程，它一直被视为Ⅲ类药物的原型。本研究旨在验证Ⅲ类抗心律失常作用与正性肌力作用可能相关的假说。我们比较了胺碘酮（可达龙）及其溶剂吐温80对自律性、不应期和肌力的影响。进行了两组实验；一组用自发搏动的大鼠心房来研究对窦房结功能的影响，另一组用电刺激左心房来研究对兴奋性、不应期和肌力的影响。1×10⁻⁴ M的胺碘酮使自发心率降低了13%，并使窦房结恢复时间延长了105%。在不影响兴奋性的情况下，胺碘酮使有效不应期延长了12%。同时收缩力增加了12%。较低浓度的胺碘酮（5×10⁻⁶ M）或吐温80没有显著影响。总之，胺碘酮在体外发挥急性电生理和肌力作用。胺碘酮的Ⅲ类抗心律失常作用与正性肌力作用相关。
