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Microelectrode technics were used to study the effects of procainamide (PA) on electrophysiologic properties of canine Purkinje fibers (PF) perfused in an extra-corporeal circuit with arterial blood of donor dogs. Donor electrocardiogram (ECG) and blood pressure (BP) and electrophysiologic properties of the isolated PF were simultaneously monitored. PA, 25 mg/kg, was administered as a single intravenous injection and plasma PA concentrations (PPAC) were determined spectrophotometrically. A decrease in PF automaticity was noted within 5-10 min of PA injection. Within 20 min, when PPAC was 10 &mgr;g/ml, amplitude and maximal rate of rise of phase 0 of the AP and conduction velocity (CV) decreased and alterations in AP duration and refractoriness were noted. BP and ECG rate were unchanged but the QRS complex had widened. At PPAC = 10-20 &mgr;g/ml (induced by further PA infusion) the aforementioned changes were accentuated. At PPAC > 20 &mgr;g/ml membrane responsiveness was significantly depressed. These experiments suggest that therapeutic PA levels rapidly decrease PF automaticity. Slowing of conduction commences later, simultaneously with changes in QRS duration. Within the same time span and range of plasma levels there are alterations in AP duration and refractoriness. Membrane responsiveness is not significantly depressed until PPAC is well into the clinically toxic range.

Canine Electrocardiographic and Cardiac Electrophysiologic Changes Induced by Procainamide