The electrophysiological effects of dicentrine on the conduction system of rabbit heart

1. The electrophysiological effects of dicentrine, an aporphine alkaloid isolated from the root of Lindera megaphylla, were examined in the Langendorff perfused rabbit heart and rabbit isolated cardiac cells. 2. Standard electrophysiological characters were measured in the Langendorff perfused rabbit heart (control study) and after 5 min exposure to 1, 3 and 9 microM of dicentrine and during the subsequent recovery phase sequentially (n = 7). The same study protocols were performed in 0.5 to 4.5 microM quinidine (n = 7), 18 to 162 microM procainamide and N-acetylprocainamide (n = 7) for comparison. 3. The results showed that the spontaneously beating heart rate and the sinoatrial (SA) and atrioventricular nodal (AH) conduction time were not significantly affected by dicentrine but were significantly suppressed by the higher doses of quinidine (4.5 microM) and procainamide (162 microM). 4. The His-Purkinje conduction time was significantly increased by the higher dose of dicentrine, quinidine and procainamide. 5. The ventricular repolarization time and its effective refractory period were significantly increased by the higher dose of dicentrine and the other agents. 6. The effective refractory period of the atrium, AV node and His-Purkinje system were also significantly increased by dicentrine and the other agents. 7. A voltage clamp study revealed that the prolongation of atrial action potential duration by dicentrine (9 microM) was associated with a significant inhibition of the transient potassium outward current. As well as inhibition of the transient outward current, a significant inhibition of the sodium inward current by dicentrine was found. 8.We conclude that (1) dicentrine is potentially a useful antiarrhythmic agent with type Ia and type III antiarrhythmic action; (2) the relative potency of dicentrine on the electrophysiological function of cardiac tissue is 10-20 times more than that of procainamide.