Why the study?
Does OPC-8212 affect ventricular arrhythmias in canine models compared to amrinone and AR-L 115?
Does OPC-8212 affect ventricular arrhythmias in canine models compared to amrinone and AR-L 115?
OPC-8212 does not worsen digitalis-induced arrhythmias in canine models, suggesting potential safety for combined therapy, though it may aggravate arrhythmias in other specific settings.
Model-specific proarrhythmic effects in canines warrant further study; leaves open clinical translation.
OPC-8212, a positive inotropic agent that increases intracellular cyclic AMP and stimulates the Ca current, was compared with amrinone and AR-L 115 in their effects on canine ventricular arrhythmias. OPC-8212, up to 3 mg kg-1, did not worsen 24 h coronary ligation arrhythmias, while it aggravated ventricular arrhythmias seen 48 h after coronary ligation. However, OPC-8212 did not at any time induce ventricular fibrillation in dogs subjected to coronary ligation. OPC-8212, up to 3 mg kg-1, had no arrhythmogenic or antiarrhythmic effect on digitalis-induced arrhythmias, while amrinone and AR-L 115 showed antiarrhythmic effects. With adrenaline-induced arrhythmias, the three drugs aggravated ventricular tachycardia to produce ventricular fibrillation. The absence of a worsening effect of the new positive inotropic agents on digitalis arrhythmia may be helpful in clinical setting of combined therapy of these new drugs with digitalis.
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Hashimoto et al. (1986) studied this question.
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