Slowing Na+ channel inactivation prolongs QT interval and aggravates adrenaline-induced arrhythmias

We investigated the effects of prolonged repolarization induced by slowed i nactivation of Na+ channel on adrenaline-induced arrhythmias in halothane a nesthetized, closed-chest dogs. We used sea anemone toxins (ATX-II and Anth opleurin-A) to prolong ventricular repolarization and examined their effect s on adrenaline arrhythmias. Sea anemone toxins prolonged the QTc- and JTc- intervals (P<0.01), but did not affect the PO interval, QRS duration, heart rate and mean blood pressure. Although sea anemone toxins did not induce a ny arrhythmias by themselves, under the treatment with these toxins, arrhyt hmias were induced by non-arrhythmia-inducing doses of adrenaline in four d ogs out of seven and the control arrhythmias induced by adrenaline were agg ravated. These results indicate that, similar to the inhibition of K+ chann els by class III drugs, which we have already reported, slowing Na+ channel inactivation with QTc prolongation also aggravates adrenaline-induced arrh ythmias.