Summary
26 mongrel dogs were given a single dose of 0.03 mg/kg tritium-labelled digoxin, β-methyldigoxin, digitoxin or ouabain 2 hrs or 95 hrs following experimental coronary occlusion. Examination of the epicardial ECG was performed by moving from intact to ischemic or necrotic zones. 60 min after glycoside administration the animals were sacrificed and tissue samples from the marked heart muscles areas and from the skeletal muscle were analysed for glycoside content. The early glycoside uptake in acute ischemic or necrotic myocardium was diminished independently of the physicochemical properties of the glycoside. Significantly higher glycoside concentrations (ng/g wet weight) were measured in the injured myocardium 3 hrs after coronary occlusion than 96 hrs afterward (p<0.005). The values in acute ischemic myocardium varied considerably. This non-homogeneity of glycoside uptake in the acute ischemic heart muscle may partly explain the increased sensitivity to glycosides in myocardial infarction. The decline of glycoside concentration correlates with the alterations in the epicardial ECG. The cardiac effects of cardenolides 60 min after intravenous administration was caused by the unchanged glycoside.
In contrast to the myocardium, glycoside accumulation could not be found in the skeletal muscle. The concentrations of digoxin, β-methyldigoxin and digitoxin in the skeletal muscle were significantly higher than the concentration of ouabain, which was rapidly eliminated via the urine.
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This study was supported by the Deutsche Forschungsgemeinschaft.
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Kuhlmann, J., Kötter, V., von Leitner, E. et al. Concentration of digoxin, methyldigoxin, digitoxin and ouabain in the myocardium of the dog following coronary occlusion. Naunyn-Schmiedeberg's Arch. Pharmacol. 287, 399–411 (1975). https://doi.org/10.1007/BF00500041
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DOI: https://doi.org/10.1007/BF00500041