Antifibrillatory effect of GYKI-23107 in induced ventricular vulnerability by local cooling and programmed...

We tested GYKI-23107 a new agent with local anaesthetic activity, in experimentally induced life-threatening ventricular arrhythmias in pentobarbitone-anaesthetized dogs. By a cooling test and programmed stimulation ventricular fibrillation was induced before and after drug administration (8 mg/kg i.v., n = 14 and 20 mg/kg i.d., n = 12). Comparative experiments were carried out with lidocaine (10 mg/kg). In this lidocaine-treated group, ventricular fibrillation could be produced at 27.7 +/- 6.6 (S.D.) min, n = 12, while after GYKI-23107 ventricular fibrillation occurred at 46.6 +/- 10.7 min, n = 14. The new compound was well absorbed from the intestines; after i.d. administration it could prevent or reduce the onset of lethal arrhythmia for more than 40 min. Its i.d. efficacy correlated well with that of i.v. administration. GYKI-23107 appears to be a safe and potent long-acting agent against ventricular dysrhythmias. It may be a promising and valuable alternative to currently available antiarrhythmic agents. The strong antifibrillatory action observed in ischaemic canine heart (n = 5) both after i.v. or i.d. administration is of special importance.