Interaction of ischemia and reperfusion with subtoxic concentrations of acetylstrophanthidin in isolated cardiac ventricular tissues: effects on mechanisms of arrhythmia.

The aim of this study was to determine if "ischemia" and/or reperfusion potentiate digitalis toxicity through effects on oscillatory afterpotentials. Isolated canine Purkinje tissue-papillary muscle preparations were studied using standard microelectrode techniques. Tissues were superfused for 10 min with an "ischemic" solution that mimicked hypoxia, acidosis, elevated lactate, zero substrate and normo- or hyperkalemia. Reperfusion with "normal" Tyrode's solution was then reinstated for 60 min. Next, subthreshold oscillatory after potentials were induced with acetylstrophanthidin (ACS) and the protocol was repeated with ACS in all solutions. Without ACS, ischemic conditions with 4 mM KCl caused depolarization of Purkinje and muscle tissues. Reperfusion resulted in hyperpolarization of Purkinje tissue followed by mild depolarization, and then recovery. Purkinje tissue exposed to ischemic conditions with hyperkalemia responded similarly, except that hyperpolarization upon reperfusion was absent. In the presence of ACS, ischemic conditions with 4 mM KCl abolished oscillatory afterpotentials and caused marked depolarization of Purkinje tissue. Reperfusion decreased the coupling intervals and increased the amplitude of oscillatory afterpotentials relative to pre-ischemic levels, and frequently elicited arrhythmic activity. Arrhythmias ceased and tissues recovered by 60 min of reperfusion. Ischemic conditions incorporating hyperkalemia also abolished ACS-induced oscillatory afterpotentials and delayed their reappearance upon reperfusion. All other reperfusion responses were similar. This study demonstrates that "ischemic" suppresses oscillatory afterpotential-mediated effects of digitalis in canine Purkinje tissue, whereas reperfusion potentiates oscillatory afterpotential-induced arrhythmias.