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 x 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 x 10-6-10-5 M), but were prolonged by high concentrations (3 x 10-5-10-4 M). Lignocaine (3 x 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.