Effects of Cardiac Glycosides on the Cell Membrane Active Transport of Sodium Ions

A RECENT editorial in this journal 1 comments on the difficulty of establishing a physiological basis for the clinical, electrocardiographic, and hemodynamic effects of cardiac glycosides on the hearts of patients with heart disease. It is now accepted that heart muscle is not a syncytium, but consists, like other organs, of discrete cells.2 Accordingly, measurements of cardiac function reflect the integrated activity of multiple cellular units, and an analysis of the effects of a pharmacological agent may logically begin with a discussion of its action on the single heart muscle cell. A consideration of the effects of cardiac glycosides at the cellular level aims at a reformulation of their mechanism of action, taking into account current concepts of the ultrastructure, physiology, and enzyme chemistry of the myocardial cell membrane and contractile apparatus. Since these drugs act most strikingly on failing hearts, such a reformulation necessarily bears on the cellular basis of heart muscle failure. This article describes in nontechnical terms the effects of cardiac glycosides on the transport of ions through the cell membrane, and considers the mechanisms by which these drugs may affect the contractile function of the myocardial cell. Although these agents have important physiological effects on other tissues, this presentation is restricted to heart muscle. As a framework for discussion, it is con-