ANTIARRHYTHMIC AND PROARRHYTHMIC EFFECTS OF SEMATILIDE IN CANINE VENTRICULAR ARRHYTHMIA MODELS

Using canine ventricular arrhythmia models induced by two-stage corona ry ligation, digitalis, adrenaline, coronary ligation and reperfusion, and programmed electrical stimulation (PES), we examined the antiarrh ythmic or proarrhythmic effects of sematilide, ylamino)ethyl]-4-[(meth ylsulfonyl)amino]-benzamide hydrochloride. Sematilide in an intravenou s (i.v.) dose range of 0.3 to 6.0 mg/kg prolonged the QTc interval, bu t had an antiarrhythmic effect only on the arrhythmias induced by PES (7 out of 10 dogs with old myocardial infarction). Sematilide was not effective on coronary ligation and reperfusion arrhythmia or the spont aneously occurring automaticity arrhythmias induced by two-stage coron ary ligation, digitalis and adrenaline, respectively, and even aggrava ted digitalis- and adrenaline-induced arrhythmias. These results indic ate that the class III agent sematilide is similar to other new class III agents, such as d-sotalol, E-4031 and MS-551, in that it was not e ffective on the automaticity arrhythmias, but different from these new class III agents, in that sematilide prevented only the induction of ventricular arrhythmias induced by PES and did not suppress the corona ry Ligation-reperfusion arrhythmias. The PES induced arrhythmias are t hought to be induced exclusively by a reentrant mechanism, but the rep erfusion arrhythmias may involve not only re-entry, but also automatic ity, and we reported the effectiveness of MS-551, E-4031 and d-sotalol on the latter arrhythmia. Sematilide is different in that it even agg ravated some automaticity arrhythmias.