AJP - Heart and Circulatory Physiology, Vol 243, Issue 4 517-H522, Copyright © 1982 by American Physiological Society
Age-related effects of digoxin on myocardial contractility and Na-K pump in sheep
T. J. Hougen and W. F. Friedman
The age-dependent effects of an acute nontoxic, positively inotropic dose
of digoxin on myocardial monovalent cation active transport were determined
in fetal, newborn, and adult sheep. Thirty-five lightly sedated,
closed-chest animals were instrumented to record electrocardiogram, left
ventricular (LV) pressure, and rate of change of LV pressure (LV dP/dt).
Ouabain-inhibitable uptake of Rb+ (86Rb+) was measured in both right
ventricular (RV) and LV slices from control animals and in animals infused
with [3H]digoxin (0.04 mg/kg) sufficient to cause an increase in LV dP/dt
without toxicity. Sixty minutes after digoxin, LV dP/dt increased 123% over
base-line values in fetuses, 131% in newborns, and 165% in adult animals.
RV and LV myocardial digoxin concentrations were similar in all groups. Rb+
active transport was significantly reduced in both RV and LV tissue from
all animals 60 min after digoxin. Control animals showed no significant
changes in contractility or Rb+ active transport among the control group of
fetal, newborn, or adult sheep. Acute infusions of digoxin increased LV
contractility in each age group and was accompanied by digoxin-induced
inhibition of myocardial Rb+ active transport. No age-related differences
in the extent of Rb+ active transport among control or among
digoxin-treated animals were observed under these experimental conditions.
These studies suggest that the differential response to the therapeutic and
toxic effects of digoxin in sheep of various ages does not reside in an
age-dependent response of the myocardial sodium pump to digoxin.
