Comparison of the electrophysiological effects of Org 7797, disopyramide, mexiletine and propafenone in anaesthetized dogs with myocardial infarcts

Abstract

1. The electrophysiological effects of intravenously administered Org 7797 were compared with those of disopyramide (class Ia), mexiletine (Ib) and propafenone (Ic) in anaesthetized dogs with 5-6 day-old left ventricular myocardial infarcts. 2. Org 7797 (0.5 mg kg-1) slowed conduction at all levels of the myocardium as shown by increases in St-A, AH, HV and QRS intervals, very modestly prolonged atrial and ventricular refractory periods and slightly shortened ventricular repolarization. Sinus node recovery time was increased whilst the RR interval was unchanged. A higher dose (2 mg kg-1) prolonged RR and rendered 5 out of 8 dogs unable to follow an atrial pacing stimulus of mean cycle length 322 ms. 3. Electrophysiological changes induced by propafenone (2 mg kg-1) were qualitatively similar to those of Org 7797 (0.5 mg kg-1). 4. Electrophysiological changes induced by mexiletine (2 mg kg-1) were small or insignificant. The most noticeable effect was a modest increase in the St-A interval and a slight shortening of ventricular repolarization. A higher dose (8 mg kg-1) additionally slowed conduction in the His-Purkinje system and in the ventricular myocardium. 5. Disopyramide (2 and 5 mg kg-1) prolonged all cardiac intervals including JTc, QTc and QT during pacing and prolonged cardiac refractory periods. 6. It was concluded that the electrophysiological profile of Org 7797 is more like that of the Ic agent propafenone than that of the class Ia and Ib drugs, disopyramide and mexiletine.