Age-related effects of digoxin on myocardial contractility and Na-K pump in sheep.
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.
D000818:Animals; D000831:Animals, Newborn; D001693:Biological Transport, Active; D004077:Digoxin / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D011247:Pregnancy; D012413:Rubidium / Q000378:metabolism; D012756:Sheep; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D004077:Digoxin; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium; D011188:Potassium