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 x 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 x 10(-6)-10(-5) M), but were prolonged by high concentrations (3 x 10(-5)-10(-4) M). 4. 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. 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.
Nezasa
Y
Y
Department of Circulation and Respiration, Nagoya University, Japan.
Kodama
I
I
Toyama
J
J
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001283:Atrioventricular Node / Q000187:drug effects; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006329:Heart Conduction System / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D011817:Rabbits; D016276:Ventricular Function
D000889:Anti-Arrhythmia Agents; D010879:Piperazines; D015363:Quinolones; C061263:8-methyl-3-(4-methyl-1-piperazinyl)-2(1H)-quinolinone; D008012:Lidocaine