QT-prolonging class I drug, disopyramide, does not aggravate but suppresses adrenaline-induced arrhythmias. Comparison with cibenzoline and pilsicainide

We investigated the effects of class I antiarrhythmic drugs on corrected QT (QTc) interval and adrenaline-induced arrhythmias in halothane-anaesthetiz ed. closed-chest dogs. For this purpose, we plotted a dose-response curve f or adrenaline by calculating the arrhythmic ratio, which is the number of v entricular ectopic beats induced by adrenaline divided by the total heart r ate, and observed the changes in the arrhythmic ratio-adrenaline dose relat ion before and after administration of class I drugs. Disopyramide and cibe nzoline decreased the arrhythmic ratio induced by adrenaline. Disopyramide prolonged the QTc interval by 20% (P < 0.01), but cibenzoline did not. Pils icainide prolonged the QTc interval (12%), but this drug did not change the arrhythmic ratio. These results indicate that in contrast to the class III drugs which we have reported earlier, i.e. 1,3-dimethyl-6-(2-[N-(2-hydroxy ethyl)-3-(4-nitrophenyl)-propylamino]ethylamino)-2,4 (1H,3H)-pyrimidinedion e hydrochloride (MS-551), 1-(2-amino-4-methanesulfonamidophenoxy)2-[N-(3,4- dimethoxyphenethyl)-N-methylamino]ethane hydrochloride (KCB-328) and E-1-([ (5-(4-chlorophenyl)-2-furanyl)methylene]amino)-3-[4-(4-methyl-1-piperazinyl )butyl]-2,4-imazolidinedione dihydrochloride (azimilide), class I drugs do not aggravate adrenaline-induced arrhythmias even though some drugs prolong the QTc interval. (C) 2000 Published by Elsevier Science B.V.