SD3212, a new antiarrhythmic drug, raises atrial fibrillation threshold inisolated rabbit hearts

SD3212 is a new antiarrhythmic drug which has class I, III, and IV effects. The purpose of this study was to elucidate the electrophysiological effect s of this compound on a rabbit atrial fibrillation model, and to test a hyp othesis that atrial fibrillation threshold is a quantitative indicator of a trial vulnerability. Whole hearts were excised from rabbits, and the aortas cannulated to perfuse the coronary arteries. Atrial fibrillation was induc ed with a burst stimulation of 50 Hz for 1 s while 3 mu M acetylcholine (AC h) was perfused. When the right atrial appendage was paced at 200-ms interv als, SD3212 prolonged interatrial conduction time: control 30 +/- 1.2 ms, A Ch 33 +/- 1.4 ms, ACh +/- SD 1 mu M 37 +/- 2.4 ms, ACh + SD 3 mu M 52 +/- 8 .1 ms. The drug also prolonged the effective refractory period: control 80 +/- 3.0 ms, ACh 48 +/- 3.5 ms, ACh + SD 1 mu M 65 +/- 4.7 ms, ACh + SD 3 mu M 98 +/- 15 ms, The rate of induction of atrial fibrillation by rapid paci ng was 26% in Tyrode's solution, 85% in the presence of ACh, and 38% in the presence of ACh + SD 1 mu M. The atrial fibrillation threshold decreased f rom 8.6 +/- 0.8 mA (control) to 2.5 +/- 0.7mA in the presence of ACh. It in creased again to 7.8 +/- 1.0 mA in the presence of SD3212 (1 mu M). SD3212 prolonged both the conduction time and refractory period. A reversed use-de pendency was not prominent. These features caused antifibrillatory effects. Thus, the atrial fibrillation threshold seems to be a good quantitative in dicator of atrial vulnerability.