R56865, AN ANTIARRHYTHMIC DRUG WITH CLASS-III EFFECTS THAT TERMINATES OUABAIN-INDUCED VENTRICULAR-TACHYCARDIA IN AN INVERSE RATE-DEPENDENT MANNER

Objective: R56865 has been described as a substance that protects cells from intracellular Na+ and Ca2+ overload. The aim of this study was to investigate its mechanism of action, which is at present unknown. Methods: The haemodynamic and (rate dependent) electrophysiological effects of R56865 (10.48 mg.kg-1) were examined and compared with its antiarrhythmic effect on ouabain-induced ventricular tachycardia (n=10), and ventricular tachycardia occurring within 24 h of occlusion of the left anterior descending artery (n=8). The experiments were all performed in dogs. Results: In anaesthetised dogs R56865 increased (p<0.05) the cycle length of the sinus rhythm, the corrected QT duration (+8%) and the effective refractory period (+16%) of the right ventricle. No rate dependency was found. R56865 had no effect on blood pressure, conduction, or refractoriness of the AV node, nor on conduction in the ventricle. In conscious dogs, R56865 did not change the cycle length of the sinus rhythm, but it did increase the QT duration (+5%, p<0.05). The cycle length of the slower ouabain induced ventricular tachycardias which were terminated by R56865 increased to a greater extent (+55%) than that of the non-suppressible, faster ventricular tachycardias (+16%): 335(SD 30) ms, n=5 v 285(10) ms. n=5. The effect of R56865 on ventricular tachycardias 24 h after infarction was considered to be of minor antiarrhythmic importance. Conclusions: R56865 has (1) class III effects. (2) a partial effect in terminating ouabain induced ventricular tachycardias which is inverse rate dependent, and (3) a weak effect on ventricular tachycardias 24 h after infarction.