MYOCARDIAL DIGOXIN UPTAKE: DISSOCIATION BETWEEN DIGITALIS‐INDUCED INOTROPISM AND MYOCARDIAL LOSS OF POTASSIUM

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Abstract
1 The time course of myocardial uptake of digoxin, of increase in inotropic effect and of changes in myocardial potassium content were studied following a single intravenous dose of digoxin. 2 Nineteen dogs with intact circulation were investigated by the use of a biopsy technique which allowed samplings before and 10, 30, 60, and 90 min after administration of digoxin. 3 The myocardial concentration of digoxin was 196 × 10−9 mol/kg 10 min after administration of digoxin. Uptake continued at a slower rate, maximum concentration being 293 × 10−9 mol/kg at 60 minutes. 4 The inotropic effect increased parallel with the uptake of digoxin; 10 min after digoxin, contractility was 127% of the control value and this increased to 139% at 90 minutes. 5 Myocardial potassium content was slightly increased 10 min after digoxin, suggesting an initial stimulation of membrane Na+-K+ ATPase. A subsequent significant fall in the myocardial potassium content probably reflects ATPase inhibition. 6 The temporal dissociation between the early onset of the positive inotropic effect and the delayed inhibition of membrane Na+-K+ ATPase indicates that inotropism of digitalis glycosides is not mediated by the same binding site as that responsible for inhibition of Na+-K+ ATPase.