The ineffectiveness of traditional antiarrhythmic agents in preventing
sudden cardiac death has increased the interest in drugs that prolong refractoriness.
Ambasilide is a new
potassium channel blocking agent that appears to prolong refractoriness at short and long cycle lengths. We assessed the effects of
ambasilide, 5 mg/kg intravenous (i.v.) bolus plus 5 mg.kg-1.hr-1 i.v. infusion, in 16 anesthetized cats in which ventricular arrhythmias could be induced reproducibly by the combination of acute
myocardial ischemia and increased sympathetic activity.
Ambasilide decreased heart rate and blood pressure and prolonged QRS duration (26%, p < 0.05), QTc (17%, p < 0.0001), and JTc (16%, p < 0.005).
Ambasilide also shifted the strength-interval curve for ventricular refractoriness by 17 to 22 msec to the right (p < 0.001).
Ventricular fibrillation was observed in 7 animals and never occurred after
ambasilide (p < 0.001); however, 4 (57%) of these cats had sustained
ventricular tachycardia requiring
cardiac massage.
Ambasilide prevented
nonsustained ventricular tachycardia in 2 (40%) of 5 animals. The antiarrhythmic effect of
ambasilide persisted when heart rate was kept constant by atrial pacing. In no case was proarrhythmia observed.
Ambasilide had a significant electrophysiologic effect at the ventricular level in the cat because it did prolong QTc and ventricular refractoriness. Therefore
ambasilide showed an antifibrillatory effect but provided only a partial protection against lethal arrhythmias induced by acute
myocardial ischemia and sympathetic activation.