Electrophysiological actions of dantrolene sodium in isolated sinoatrial and atrioventricular nodes and in a model of ischemia.

Recent experiments have suggested that the electrophysiological actions of dantrolene sodium in cardiac tissues may be mediated in part by slow inward current blockade. The authors report here the effects of this agent in tissues the electrical activity of which depends mainly on the slow inward current. In isolated rabbit sinoatrial node tissue, dantrolene (35.1 microM) significantly diminished maximal diastolic potential, action potential amplitude and upstroke velocity, and it prolonged action potential duration and spontaneous cycle length. Most effects were reversible upon washout. In isolated rabbit atrioventricular nodal tissue, dantrolene diminished action potential amplitude, delayed activation time, prolonged refractoriness and led to frequency-dependent block, also in a reversible manner. Through these actions, dantrolene showed an antiarrhythmic effect by preventing atrioventricular nodal reentry in the form of atrial "echoes." These results support the hypothesis that dantrolene inhibits slow inward current and suggest that, at adequate doses, it might effectively suppress supraventricular arrhythmias in patients. In a third group of experiments, addition of dantrolene (35.1 microM) to the central segment of a canine Purkinje fiber in an "ischemic gap" preparation led to conduction impairment. Consequently, reflections were obtained at relatively slow frequencies, whereas, at faster frequencies, the incidence of reflection was reduced. These effects were similar to those previously reported for other agents such as lidocaine and verapamil. The authors conclude that dantrolene behaves as a calcium channel blocking agent and has potential value as an antiarrhythmic drug.