Digoxin Treatment and Congestive Heart Failure in Light of Human Cardiac and Skeletal Muscle Digitalis Glycoside Receptor Studies

Abstract

Previous studies carried out on various in vitro systems (1,3,19) and experimental animals (2,18) have reported an increase in Na⁺/K⁺-ATPase as a result of cardiac glycoside exposure, as have studies performed on human peripheral blood cells (4,11). This has engendered speculation about development of tolerance to the inotropic effect of cardiac glycoside treatment: The idea being that inhibition of Na⁺/K⁺-ATPase obtained initially by digitalization would be counterbalanced by Na⁺/K⁺-ATPase upregulation. However, points of concern may be raised with regard to the methodology of the underlying studies for this hypothesis: 1) The concentrations of cardiac glycoside applied to cell cultures were in micromolar concentration, i.e. toxic to humans 2) In vitro systems, peripheral blood cells and results obtained by digitalization of normal guinea pigs or rats need not mirror the effect of digitalis treatment on human cardiac and skeletal muscle in heart failure. 3) Activity measurements performed on purified membrane fractions may not be applicable for studying quantitative aspects of Na⁺/K⁺-ATPase in muscle tissue (5). On this background it was our aim to evaluate the hypothesis that cardiac glycoside treatment increases digitalis receptors by performing appropriate measurements on the tissue of relevance, i.e. cardiac and skeletal muscle from patients with heart failure. In addition we wished to assess the distribution of specifically bound digoxin to human muscular tissue during digitalization.