RATE-DEPENDENT EFFECTS OF DETAJMIUM AND PROPAFENONE ON VENTRICULAR CONDUCTION AND REFRACTORINESS IN ISOLATED GUINEA-PIG HEARTS

Detajmium (4-[3'-diethylamino-2'-hydroxypropyl]-ajmalin) is an Na+-cha nnel-blocking drug with an extremely long recovery from use-dependent sodium channel block. The aim of the present study was to investigate the rate-dependent effects of detajmium on the intraventricular conduc tion of isolated, spontaneously beating, guinea pig hearts in comparis on with the effects of propafenone. Detajmium (0.3 mu M) and propafeno ne (0.3 mu M) caused comparable prolongations of the intraventricular conduction time during sinus rhythm. The time to steady state of the r ate-dependent QRS prolongation during rapid ventricular pacing follows an exponential function of the beat number after an abrupt change of frequency and is characterized by a drug-specific time constant. This time constant was significantly longer for detajmium (tau = 265 +/- 16 5 beats; mean +/- SEM; n = 6) than for propafenone (tau = 31 +/- 4 bea ts; n = 11; p < 0.01). In the presence of propafenone, QRS duration pe aked initially before decreasing to a steady state. Detajmium, in cont rast, progressively broadened the QRS complex. Both substances caused the greatest increase in the ventricular effective refractory period ( V-ERP) when the number of conditioning stimuli (interstimulus interval , 120 ms) was in the range of the time constant. However, when the num ber of conditioning stimuli was further increased, the V-ERP for propa fenone diminished progressively. In conclusion, propafenone displayed, in comparison with detajmium, only a transient rate-dependent effect on intraventricular conduction and V-ERP.