Antiarrhythmic and electrophysiological actions of flecainide, bepridil and amiodarone on isolated heart preparations during controlled hypoxia.

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.