Barucainide, a novel class Ib antiarrhythmic agent with a slow kinetic property: electrophysiologic observations in isolated canine and rabbit cardiac muscle

Electrophysiologic effects of barucainide hydrochloride on the transmembrane potentials of isolated canine and rabbit cardiac muscle were investigated by means of a standard microelectrode technique. Barucainide (10(-6) to 3.0 x 10(-5) mol/L) produced concentration-dependent inhibition of the maximum upstroke velocity (Vmax) in canine Purkinje fibers and ventricular muscle. Tonic block of Vmax was small and negligible. Barucainide produced marked use-dependent block (UDB). The onset rate of UDB and the speed of recovery from UDB were comparable to those of disopyramide. The recovery time constant was 8.0 +/- 0.8 seconds. Membrane depolarization induced by high concentrations of potassium enhanced the inhibitory action of barucainide on Vmax. The enhancement of tonic block was much greater than that of UDB indicating a selective effectiveness of the drug in pathologically depolarized tissues. Barucainide produced marked shortening of the action potential duration (APD), which indicates that barucainide exerts class Ib antiarrhythmic effects. Such shortening effects on the APD were not affected by pretreatment with 1 mmol/L cobalt or with 0.5 mmol/L 4-aminopyridine. In contrast, barucainide had no marked effects on the APD in the presence of 4.0 x 10(-5) mol/L lidocaine, although it produced almost the same extent of Vmax inhibition as did barucainide alone. Frequency of the pacemaker activity in the rabbit sinoatrial tissue and of the automaticity at normal resting potential in Purkinje fibers enhanced by 2.0 X 10(-6) mol/L isoproterenol were significantly suppressed by barucainide. However, barucainide up to 3.0 x 10(-5) mol/L failed to suppress the firing frequency of the abnormal automaticity in canine Purkinje fibers induced by 5 mmol/L barium. These overall findings indicate that barucainide is a novel class Ib antiarrhythmic agent which, unlike Other Ib agents, has a slow kinetic property. However, the precise significance of this unique electrophysiologic feature with respect to the antiarrhythmic action of the drug is not known but provides the basis for understanding the relationship of electrophysiologic effects of barucainide in vitro and its potential antiarrhythmic actions in experimental Animals and in humans.