Electropharmacology of bidisomide in the normal intact canine heart

Bidisomide (SC‐40230) is a class I antiarrhythmic agent. The effects of bidisomide on the electrophysiology of the intact heart were studied using an anesthetized dog model. Three cumulative intravenous doses of bidisomide were studied (n = 5)—1.5, 11.5, and 22.1 mg/kg—given as a loading dose followed by a maintenance infusion to produce three plasma concentration ranges—1.9‐–2.3, 17.2–21.2, and 22.7–24.1 μg/ml. A placebo group (n = 5) received the equivalent volume of saline. Heart rate, blood pressure, lead II electrocardiogram (ECG) intervals, as well as conduction, refractoriness, and nodal function were measured. Placebo had no effect on any parameter. With the exception of prolonging the atrial refractory period, bidisomide had no effect on any parameter at the lowest dose studied. Bidisomide caused a dose‐dependent and statistically significant increase in sinus node recovery time, atrial and ventricular conduction time, atrial effective refractory period, A‐H and H‐V intervals, P‐R and QRS intervals, Wenckebach point, and spontaneous cycle length. The effect of bidisomide on atrial refractory period and on A‐H interval was cyclelength dependent. Bidisomide increased or did not change ventricular refractory period in the five dogs studied. Blood pressure decreased less than 15% at plasma bidisomide concentrations up to 20 μg/ml. These experiments demonstrated that bidisomide affects conduction and/or refractoriness in all parts of the heart and has electrophysiologic effects consistent with ventricular and supraventricular antiarrhythmic activity.