Effects of OPC‐88117, a new antiarrhythmic agent, on the electrophysiological properties of rabbit isolated hearts

Abstract

Effects of a new antiarrhythmic agent, OPC‐88117, on the conduction properties and excitability of Langendorff‐perfused rabbit hearts were compared with those of lignocaine. OPC‐88117 above 10−5 m caused a significant prolongation of atrio‐His bundle conduction time (A‐H interval) as well as His bundle‐ventricular conduction time (H‐V interval). Lignocaine above 10−5 m caused a similar prolongation of H‐V interval with a minimum change of A‐H interval. The conduction time from His bundle stimulus to the left ventricle (St‐LV) at a low frequency (1 Hz) was also prolonged by these drugs around 10−4 M. OPC‐88117 above 3 × 10−6 m prolonged the effective and functional refractory periods of His bundle (ERPHB, FRPHB) as well as the effective refractory period of left ventricular muscle (ERPVM) in a dose‐dependent manner. ERPHB, FRPHB and ERPVM were, shortened by low concentrations of lignocaine (3 × 10−6‐10−5 M), but were prolonged by high concentrations (3 × 10−5‐10−4 M). Lignocaine (3 × 10−6‐10−4 M) induced an upward displacement of the His bundle refractory curve, indicating a greater intraventricular conduction delay for premature excitation. In experiments with OPC‐88117, such an upward displacement was observed only at 10−4 M. These results suggest that the primary electrophysiological effect of OPC‐88117 is a lengthening of ventricular refractoriness, and that at high concentrations it may also exert lignocaine‐like inhibition of ventricular conduction.

Electropharmacology of OPC‐88117, A New Antiarrhythmic Agent

“…At 3 X M , ERP,, and FRP,, were prolonged by 33 and 28%, respectively, on average (n = 5). At M OPC-88117, a slight prolongation of St-LV interval was observed in addition to a further prolongation of ERPHB and FRPHB (19). Figure 7 illustrates refractory curves of His bundle in the absence and presence of OPC-88 1 17 or lidocaine.…”

“…Effects of OPC-88 1 17 on the cardiac conduction properties and excitability were examined in Langendorff-perfused rabbit hearts and compared with those perfused with lidocaine ( 19). Effects of the two drugs on the atrioventricular conduction were Significantly different from control at p < 0.05.…”

“…Control values of ERPHB and FRPHB were 327.8 -t 5.9 ms and 356.0 rfr. 4.7 ms, respectively (n = 10) (19).…”

“…Effects of OPC-88 1 17 on the cardiac conduction properties and excitability were examined in Langendorff-perfused rabbit hearts and compared with those perfused with lidocaine ( 19). Effects of the two drugs on the atrioventricular conduction were tested in each of the five hearts under right atrial stimulation at a constant cycle length of 400 ms. His bundle electrograms (HBE) were recorded through a pair of bipolar stainless steel electrodes with an interpolar distance of I .0 mm.…”

“…Ventricular excitation was recorded through a pair of bipolar electrodes placed on the epicardial surface of left ventricle (LV) near the apex. Under the His bundle stimulation at a basic cycle length of 1,000 ms, the control values of the interval from the stimulus to the left ventricle (St-LV) was 34.5 k 1.7 ms (n = 10) ( 19). To obtain the effective refractory period of His bundle (ERPHB) and the functional refractory period of His bundle (FRPHB), a premature stimulus (S2) was applied through the His bundle stimulating electrodes with various coupling intervals, at every tenth basic stimulus.…”