To evaluate the effects of programmed ventricular stimulation on resultant plasma concentrations of intravenously administered
procainamide,
drug dosing was performed with and without ventricular stimulation on two separate days (48 hours apart) in 12 dogs (13 dosing trials) at > or = 14 days after
myocardial infarction (mean: 62 days). During
infarct surgery, three bipolar
electrodes were plunged into left ventricular epicardium, externalized, and later used for ventricular stimulation. On the first study day,
procainamide was dosed to achieve two sequential plateau plasma levels (I and II), with a 20-minute equilibrium period at each plateau before ventricular stimulation. Plasma
procainamide concentrations were measured before initiation of ventricular stimulation and at the completion of ventricular stimulation for each sequential plateau level. Stimulation involved delivery of one, two, and three extrastimuli at three paced cycle lengths at three left ventricular sites before
procainamide dosing and at each of the two
procainamide plateau levels. Three dogs were excluded from analysis due to induction of lethal ventricular arrhythmias. No ventricular arrhythmias were induced in the remaining nine animals. On the second study day,
procainamide was dosed identically, but no ventricular stimulation was performed. Intravenous
drug administration and collection of plasma concentration samples were performed with +/- 1 minute on both study days. Mean plasma
procainamide concentrations at the end of ventricular stimulation at dosage Levels I & II were 10% and 12% greater (P < 0.02 and P < 0.005, respectively) than plasma concentrations measured at comparable times on the study day when no ventricular stimulation was performed.(ABSTRACT TRUNCATED AT 250 WORDS)