Comparison of the Digitalis Receptor in Erythrocytes from Preterm Infants and Adults

Abstract

ABSTRACT. We compared adrubidium by erythrocytesThe membrane Na", K' , ATPase is considered by most auof preterm infants and adults as a measurement of their thorities to be the pharmacologic receptor for digitalis glycosides Na+, K+, ATPase enzyme system. In neonates, total uptake (7). By specifically inhibiting this enzyme, higher intracellular (0.92 2 0.13 pg/106 cells) and specific uptake (0.64 f concentrations of sodium are achieved; exchange of increased 0.076 pg/106 cells) were significantly higher than in adults amounts of sodium with more extracellular calcium results in (0.52 f 0.1 and 0.29 2 0.06 pg/106 cells, respectively; p < increased cardiac ionotrophy (8). However, the mechanism of 0.025). The percentage of specific uptake from total uptake action of digitalis in increasing cardiac inotrophy is still largely was higher in infants (73.3 2 2.3%) than in adults (57.9 f conjectural. 4.6%) ( p < 0.005). No differences were found in the affinityRb is a kaliumimetic cation that moves across cell membranes constant of 86Rb uptake between infants (4.35 f 0.48 ng/ in a fashion similar to potassium (9). Thus, by measuring Rb+ ml) and adults (4.85 2 0.48 nglml). Stratification of infants uptake, one may assess the activity of the membrane Na+, K", according to their serum K+ concentrations revealed that ATPase enzyme both in terms of binding capacity and affinity levels above 5.4 mEq/liter were associated with a higher (10). Rb, rubidiumAll were hospitalized in our neonatal ICU because of prema- RBC, red blood cellsturity, suspected sepsis, or respiratory distress syndrome. Twelve healthy adult volunteers served as a second group for the 86Rb Bmax, total specific uptake capacity uptake studies.Clinical studies. At the day of the study 1-ml heparinized blood samples were drawn from an existing intravenous indwellDespite continuous controversy over their clinical efficacy, ing catheter for 86Rb uptake studies. Electrolytes and creatinine digitalis glycosides are still one of the most commonly prescribed were determined in the serum and in 6-8 h urine collection. group of drugs (1). In infants and children, only a few controlled Creatinine clearance and fractional excretion of sodium and studies assessed the effect of digoxin in heart failure associated potassium were determined using standard methods. In each with congenital heart defects, and their results are inconclusive infant, potassium intake was calculated for the 2 days before the (2). Pharmacokinetic analysis has revealed that infants and chil-study and during the day of the study. dren need higher doses per kg of digoxin than adults to achieve 86Rb uptake studies. For the uptake assay of Rb in RBC the comparable serum concentrations due to faster clearance rates method described by Aronson et al. (1 1) was used with some (3). However, in some cases these differences are minimized by modifications. calculation of dose according to surface area.Erythrocytes were separated by centrifugation and washed The hypothesis that the immature organism is less s...

Gastrointestinal Symptoms as an Important Sign in Premature Newborns with Severely Increased S‐Digoxin

“…The need for higher doses could be due to a larger concentration of N π -K π -ATPase in the myocardium (Kjeldsen & Grøn 1990). Other studies have suggested a higher erythrocyte binding capacity of digoxin (Koren et al 1988), which could provide a pharmacodynamic explanation of the increased demand of digoxin to achieve a given effect in infants compared to adults. Higher concentrations would thus be necessary for sufficient clinical effect, but the vagal effects and the risk of a critical increment in P-Potassium are still present and should be dealt with.…”