| Abstract: | 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. 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. The myocardial concentration of digoxin was 196 X 10(-9) mol/kg 10 min after administration of digoxin. Uptake continued at a slower rate, maximum concentration being 293 X 10(-9) mol/kg at 60 minutes. 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. 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. 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. |
