Experimental analysis of the anti-arrhythmic and arrhythmia-inducing actions of cyclovirobuxine D

Cyclovirobuxine D (CVB), an active principle of Buxus microphylla var. sinica, has some therapeutic effect on cardiac arrhythmia. This paper reported its effects on action potential of cardiac cells of isolated ventricular septum of guinea pig. CVB 1.2*10(-5) M prolonged conspicuously the duration of action potential (APD) and even more the effective refractory period (ERP); it depressed spontaneous activity of myocardial cell as well as rhythmic activity induced by ouabain and isoproterenol. CVB could lengthen the duration of phase 2 (APD) of action potential which had already been shortened from hypoxia. CVB (above 3.6*10(-5) M) decreased the depolarizing rate of phase 0, but evoked the diastolic depolarization, thus the cell fired spontaneously; the slowly rising response was unaffected by 75% reduction of extracellular Na+ concentration, but abolished completely by Mn2+ in bathing fluid. Over the course of 1 h following exposure to CVB, the cell lost excitability almost entirely. All these effects were reversible. It is then supposed that CVB may not only inactivate the fast inward current, but also decrease the extent of depolarization required for activation of the slow inward current (Isi), speed up the development of the activation process and slow down the inactivation process of this current component. The possible mechanisms of antiarrhythmic and arrhythmia-inducing actions as well as the underlying hazard for the clinical application of CVB were discussed.