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

1 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. 2 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. 3 OPC‐88117 above 3 × 10 −6 m prolonged the effective and functional refractory periods of His bundle (ERP HB , FRP HB ) as well as the effective refractory period of left ventricular muscle (ERP VM ) in a dose‐dependent manner. ERP HB , FRP HB and ERP VM 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). 4 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. 5 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.