Abstract
We studied tissue distribution of digoxin and its effects on myocardial performance and cardiac conduction in fetal and adult sheep. Catheters were inserted and ECG electrodes attached in 11 fetuses(109-129 d gestation)and 8 non pregnant ewes. Digoxin was infused to achieve steady state; ratio of pre-ejection period (PEP)to left ventricular ejection time(LVET), cardiac rhythm and PR interval were recorded. Digoxin concentrations were measured repeatedly in plasma, and in myocardium and midbrain after sacrifice. We achieved higher plasma digoxin concentrations in fetuses than in adult sheep, but tissue to plasma ratios were similar: midbrain/plasma-6.4 fetus, 5.3 adult; myocardium/plasma-87 fetus, 90 adult. Myocardial responses to digoxin were greater in ewes than in fetuses; a plasma digoxin concentration of 2 ng/ml reduced PEP/LVET by 0.1 in ewes, but by only 0.06 in fetuses. Cardiac rhythm disturbances occurred in 6 of 8 ewes at an average plasma digoxin concentration of 2.3 ng/ml but in only one fetus, at a plasma digoxin concentration of 9 ng/ml. PR interval prolongation was linearly related to plasma digoxin concentration in fetuses but uncommon below a plasma digoxin level of 2 ng/ml in ewes. These studies show the effects of digoxin vary with age because of differences in tissue sensitivity rather than drug kinetics and provide experimental support for high concentration digoxin therapy in young infants.
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Berman, W., Ravenscroft, P., Sheiner, L. et al. THE RELATIONSHIP OF AGE TO THE DISTRIBUTION AND PHYSIOLOGIC EFFECTS OF DIGOXIN IN SHEEP. Pediatr Res 11, 414 (1977). https://doi.org/10.1203/00006450-197704000-00269
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DOI: https://doi.org/10.1203/00006450-197704000-00269
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