In this study, we used the spontaneously beating, isolated rat right atrium as an in vitro model to study arrhythmogenic effects of electrical stimulation. A tetrapolar platinum electrode was used for stimulation and recording of atrial electrical activity at 36.5 degrees C (spontaneous rate, 4.9 +/- 0.3 Hz). A flutter-like pattern of arrhythmia was reproducibly induced by application of stimulus trains (250 pulses, 66.7 Hz), Arrhythmia was characterized by regular and very short cycle length (40-70 ms), each episode lasting from 3 s to >5 min. In control conditions, application of one to five pulse trains was sufficient to induce arrhythmia. However, atropine (but not propranolol) completely blocked arrhythmia induction (10-15 consecutive trains were ineffective). The ability of electrical stimulation to evoke arrhythmia was restored after atropine washout. A milder stimulation protocol(30 pulses, 50 Hz), which was unable to evoke arrhythmia in control conditions, was fully effective in the presence of 1 mu M acetylcholine (ACh). Furthermore, a similar flutter-like pattern could be induced in isolated left atria in the presence of ACh, Our results point out an arrhythmogenic effect of neurally released ACh in the isolated right atrium on atrial electrical stimulation.344475479