KCB-328 is a newly synthesized class III
drug. To determine whether this
drug has antiarrhythmic or proarrhythmic effects, we used canine ventricular
arrhythmia models induced by coronary
ligation and reperfusion, programmed electrical stimulation (PES), two-stage coronary
ligation, digitalis, or
epinephrine.
KCB-328, in an
intravenous infusion of 0.5 mg/kg/30 min, prolonged the QTc interval only 11%, but had antiarrhythmic effects on the reentry arrhythmias induced by PES (12 of 12 dogs with old
myocardial infarction; p < 0.05).
KCB-328, in an infusion of 1 mg/kg/h, suppressed the occurrence of fatal
ventricular fibrillation (VF) induced by coronary
ligation and reperfusion under either
halothane anesthesia (p < 0.05) or
pentobarbital anesthesia (p < 0.05). Under the
halothane anesthesia,
KCB-328 alone showed proarrhythmic effects [i.e., induction of ventricular premature contractions (VPCs)], but it did not induce a more severe effect such as
torsades de pointes-type
ventricular tachycardia (VT). In addition,
KCB-328 had weak antiarrhythmic effects on the automaticity arrhythmias induced by 24-h coronary
ligation but was effective neither on 48-h coronary
ligation arrhythmias nor on the digitalis- and
epinephrine-induced arrhythmias. Our results indicate that
KCB-328 has powerful antiarrhythmic effects with fewer proarrhythmic potencies.