Effect of procainamide and N-acetylprocainamide on atrial flutter: studies in vivo and in vitro

We studied the effects of procainamide and N-acetylprocainamide (NAPA) in a conscious dog preparation of atrial flutter resulting from circus movement around the tricuspid orifice. We also recorded transmembrane potentials of atrial tissues from the circus path in vitro. In 12 instrumented dogs, average flutter cycle length was 157 msec, the duration of the excitable gap was 73 msec, and conduction velocity was 0.75 m/sec. At 4 and 8 mg/kg, procainamide moderately prolonged cycle length, but did not terminate the flutter. At a cycle length of 300 msec procainamide increased effective refractory period (ERP) by 12% and 20% and conduction time by 8% and 19%. At 16 and 32 mg/kg procainamide prolonged cycle length, ERP, and conduction time by 60% to 80% and stopped the flutter in all trials. NAPA, at 16, 32, and 64 mg/kg, increased flutter cycle length by 16%, 16%, and 31%, ERP by 14%, 28%, and 41%, and conduction time by less than 15%. NAPA terminated the flutter in two of six dogs given 32 mg/kg, and three of five dogs given 64 mg/kg. The excitable gap was lengthened by both procainamide and NAPA. Transmembrane potentials showed that at a cycle length from 1000 to 300 msec procainamide (10 mg/liter) increased action potential duration and decreased the first time derivative of phase O of the action potential (Vmax), whereas NAPA (20 mg/liter) increased action potential duration without changing Vmax. These findings show the difficulty of relating drug effects on transmembrane potentials to efficacy in vivo since the former do not necessarily indicate which changes in cellular electrical activity are responsible for efficacy against a particular arrhythmogenic mechanism.