Observations on the biphasic nature of digitalis electrophysiological actions in the human right atrium

Cardiac electrophysiological effects of a digitalis glycoside have been investigated by right atrial intracardiac stimulation and recording in 12 patients with paroxysmal supraventricular tachyarrhythmias. Measurements were made of atrial effective refractoriness by pacing together with programmed premature extrastimulation. Simultaneous recordings of atrial action potential duration from a site close to the sinoatrial node and from a more distal atrial site were made using an endocardial contact-injury potential technique. All subjects received methyldigoxin 10.0 micrograms X kg-1 intravenously, while half were also pretreated with atropine. A biphasic response to methyldigoxin was observed, with initial action potential prolongation, maximal at 20 min post-infusion, followed by significant action potential shortening which persisted to the end of the study period at 40 min. The initial phase, that of prolongation, was associated with smaller increases in atrial effective refractoriness and increased vulnerability to atrial tachyarrhythmia initiation. During the subsequent phase of action potential shortening, the gap between the termination of effective refractoriness and completion of action potential repolarisation was narrowed, coinciding with diminished vulnerability to tachyarrhythmias. Slight but significant atrioventricular conduction delay was apparent 30 to 40 min after glycoside infusion, indicating enhanced vagal activity during the phase of action potential shortening. Prior atropinisation reduced the magnitude of both early and late components of the biphasic action potential response to digitalis, supporting the proposition that both components are mediated via cardiac muscarinic receptors. Since vagal effects on the atrioventricular junction appeared during the later phase, it is suggested that initial action potential prolongation by digitalis may have been effected via local acetylcholine release, while subsequent action potential shortening may have been caused by a combination of vagally and locally mediated activity.