The effects of doxorubicin on ventricular tachycardia

Doxorubicin, in concentrations that have no effect on fast or slow response action potentials, has been shown to suppress ouabain-induced delayed afterdepolarizations. In this study, we used standard microelectrode techniques to determine the effects of doxorubicin on isolated canine Purkinje fibers. We studied automaticity induced at normal and low membrane potentials, conduction in normal and K+-depolarized Purkinje fibers, and triggered activity induced by ouabain and by experimental myocardial infarction. Doxorubicin, 50 microM, suppressed the triggered activity and the delayed afterdepolarizations that induced it, but had no effect on the other variables. We then studied the effects of intravenous doxorubicin, 16 to 64 mg/m2 body surface area, on ouabain-induced ventricular tachycardia and the ventricular tachycardia that occurs 24 hr after ligation of the left anterior descending coronary artery in the intact dog. There was no effect on the infarct-induced arrhythmia, but concentrations of doxorubicin that had no other effect on the electrocardiogram suppressed those ouabain-induced arrhythmias that appeared to have been triggered. The automatic arrhythmias induced by ouabain were not affected. Both the latter mechanisms were verified in studies of isolated Purkinje fibers that were obtained on completion of the intact animal experiments. These results indicate that agents having high selectivity for specific arrhythmogenic mechanisms can be useful adjuncts in discriminating among the mechanisms responsible for arrhythmias in intact animals.