CPU 86017 suppression of arrhythmias induced by ischemia/reperfusion,ouabain, aconitine,and elevation of ventricular fibrillatory threshold

Protection by CPU 86017 against reperfusion-induced arrhythmias was studied in Langendorff perfused hearts and anesthetized rats. Inhibition of arrhythmias induced by ouabain and aconitine was observed, and the influence of CPU 86017 on ventricular fibrillation threshold (VFT) was determined. CPU 86017 exerted a dose-dependent antiarrhythmic effect in animal models. In Langendorff's perfused hearts, CPU 86017 significantly reduced the incidence and duration of ventricular fibrillation and ventricular tachycardia, as well as arrhythmic scores in a dose-dependent manner. The approximate ED₅₀ of CPU 86017 against ventricular fibrillation was 2.10 μM. The antiarrhythmic effect of CPU 86017 against arrhythmia persisted for more than 6 h. In anaesthetized rats, CPU 86017 provided potent antiarrhythmic and antifibrillatory effects by po or iv routes. CPU 86017 was similar in potency to propafenone by the po route, and 10 times more potent than lidocaine by the iv route. CPU 86017 significantly attenuated the exaggerated arrhythmia and ventricular fibrillation in hypertrophic hearts induced by 1-thyroxine. Against ouabain-induced arrhythmias CPU 86017 exerted a dose-dependent inhibitory effect, which was 6.5-fold more potent than berberine. CPU 86017 significantly reduced ventricular fibrillation incidence and prevented the further deterioration of ventricular arrhythmias induced by aconitine. In conclusion, CPU 86017 is a potent antiarrhythmic agent with multiple mechanisms of action. Drug Dev. Res. 39:184–190. © 1997 Wiley-Liss, Inc.