On Vagal and Extravagal Factors in Cardiac Slowing by Digitalis in Patients With Auricular Fibrillation

Abstract

The improvement of the circulation produced by digitalis in patients with auricular fibrillation is almost invariably associated with slowing of ventricular rate. Whether the improvement is the cause of the slowing, or the result of it, or in part a cause and in part a result of the slowing are matters concerning which opinion is divided. The extent to which the slowing causes the improvement could be established if the slowing could be prevented. It appeared that this problem might be attacked by the use of repeated doses of atropine to prevent the cardiac slowing over a period of several days after a massive dose of digitalis. The influence of digitalis on the heart failure as measured by changes in body weight, fluid loss, and subjective symptoms in these cases might then be compared with its well-known effect in patients in whom the rate is permitted to become slow.The effect of atropine on the heart rate of digitalized patients with auricular fibrillation has been the subject of several reports in the literature, and while views were not entirely in agreement, there seemed to be sufficient accord to indicate that with adequate doses of atropine little difficulty would be encountered in maintaining a rapid heart rate after large doses of digitalis in a considerable proportion of the patients.A study was planned to pursue this matter, but the original objective ceased to appear promising after several results were obtained, for they showed what was confirmed by subsequent observations, that the experiment could not be carried out, that atropine, even in doses causing severe systemic symptoms, could not prevent the pronounced slowing of the ventricle after very large doses of digitalis. The inference we drew from the literature, therefore, proved to be incorrect, and a reexamination of the literature disclosed the fact that the discordant observations and conflicting conclusions concerning the role of the vagus could not be harmonized by existing data alone. LITERATUREWhile there are numerous reports on the effect of atropine on the ventricular rate which has been slowed by digitalis, the studies of Cushny, Marris, and Silberberg (1), and Lewis, Drury, Wedd, and Iliescu (2) present the more detailed analyses of the subject. Cushny et al. (1) concluded that "in auricular fibrillation, digitalis and its allies slow the heart from some direct action on the heart and not from stimulation of the inhibitory mechanism, for atropine does not restore the original rate of the released heart." About 10 years later, Lewis et al. (2)

Effects of Cardiac Glycosides Injected into the Atrioventricular Node Artery of the Dog

“…The effects of digitalis on A-V conduction have been attributed to both a 'vvgally mediated' and to a direct 6extra-vagal' action (Gold et al 1939). Studies in man have shown that prolonged A-V conduction from ouabaiim, administered intravenously at moderate doses, can be prevented by prior atrspinizaticsn (Carleton et aE.…”

Clinical pharmacology: Reflections in my rear‐view mirror

“…His classic contribution on the vagal and extra vagal actions of digitalis was based on data collected and observations made with the stethoscope alone. 6 Gold's use of the stethoscope was generally applauded, but his double-blind requirement met widespread opposition. A select few came to his support by contributions to the literature in clinical pharmacology in which the doubleblind control was used with profit.…”

Effects of Ouabain, Atropine, and Ouabain and Atropine, on A-V Nodal Conduction in Man

“…Since the work of Gold (3,4 ) , it has generally been accepted that digitalis has both vagal and extravagal actions in man. The relationship of extravagal to vagal effect on A-V conduction has not been established, however, in patients with minimal or no cardiac disability.…”