Effect of low acetylcholine doses on pacemaker function and sinoatrial conduction time in isolated right atrium of dog

Spontaneous atrial fibrillation can occur following a period of acetylcholine induced arrest. The onset of fibrillation was preceded by multifocal atrial premature beats. This study was designed to determine whether physiological concentrations of acetylcholine can produce atrial premature beats. It was hypothesized that the underlyng mechanism of atrial premature beats was parasystole which required acetylcholine dependent entrance block for protection of the ectopic focus. In isolated perfused canine right atria (n=10) unipolar electrogram (250 leads) were recorded under control conditions and during infusion of 0,1 and 1,0 μM of acetylcholine. Total sino-atrial conduction time was also determined. During control period there were no spontaneous atrial premature beats and total sino-atrial conduction time was normal. During infusion of 0,1 μM and 1,0 μM of acetylcholine spontaneous atrial premature beats occurred in two and five preparations, respectively, (p=0,029). Acetylcholine caused concentration dependent prolongation of total sinoatrial conduction time from 66±30 msec (control) to 90±49 msec (0,1 μM) and 157±75 msec (1,0 μM) (p<0,001). Activation sequence maps demonstrated that an atrial premature beart and prior depolarization originated from separate sites. These data show that atrial premature hearts occur at physiologic concentrations of acetylcholine and are associated with slowing and block of sino-atrial conduction.