Dietrich H, Borchard U, Hafner D, Hirth C
Arch Int Pharmacodyn Ther. 1985 Apr;274(2):267-82.
A model of arrhythmias based on the application of sinusoidal alternating current (ac) to isolated heart preparations has been employed to determine the effects of hypoxia (30 vol % O2 in the perfusion medium) on the threshold of arrhythmia and asystole. With this method three representatives of different classes of antiarrhythmic drugs, flecainide, bepridil and amiodarone, have been investigated in isolated papillary muscles and left atria from guinea-pigs. Hypoxia reduces both the threshold for ac-arrhythmia and the threshold for ac-asystole. Flecainide (3 and 10 mumol/l) elevates both thresholds under normoxia and has a protective effect against the hypoxia-induced reduction of threshold. Bepridil (10 mumol/l) is without effect on the threshold of ac-arrhythmia in papillary muscle, prevents the hypoxia-induced decline of the threshold of ac-arrhythmia in left atria and depresses the threshold of ac-asystole both in normoxia and hypoxia. amiodarone (10 mumol/l) elevates the threshold of ac-arrhythmia both during normoxia and hypoxia in papillary muscle but only during the second hour of hypoxia in left atria. The results may be interpreted with respect to the inhibitory action on Na+-channels (flecainide), Ca2+-channels (bepridil) or protective effects against hypoxia-induced changes in action potential duration (amiodarone, but also flecainide and bepridil) as shown by additional electrophysiological experiments.
一种基于对离体心脏标本施加正弦交流电（ac）的心律失常模型已被用于确定缺氧（灌注介质中含30%体积的氧气）对心律失常阈值和心搏停止阈值的影响。采用这种方法，对豚鼠离体乳头肌和左心房中不同类别的三种抗心律失常药物——氟卡尼、苄普地尔和胺碘酮进行了研究。缺氧会降低交流电诱导心律失常的阈值和交流电诱导心搏停止的阈值。氟卡尼（3和10 μmol/L）在常氧条件下会提高这两个阈值，并对缺氧诱导的阈值降低具有保护作用。苄普地尔（10 μmol/L）对乳头肌中交流电诱导心律失常的阈值没有影响，可防止左心房中缺氧诱导的交流电诱导心律失常阈值下降，并且在常氧和缺氧条件下都会降低交流电诱导心搏停止的阈值。胺碘酮（10 μmol/L）在常氧和缺氧条件下都会提高乳头肌中交流电诱导心律失常的阈值，但仅在左心房缺氧的第二个小时会提高该阈值。如额外的电生理实验所示，这些结果可以根据对钠通道（氟卡尼）、钙通道（苄普地尔）的抑制作用或对缺氧诱导的动作电位持续时间变化的保护作用（胺碘酮，以及氟卡尼和苄普地尔）来解释。
