Key result
Infants under 6 months show ~60% higher myocardial Na,K-ATPase concentration than older children.
Why the study?
Myocardial Na,K-ATPase concentration and its age-dependent changes in children were quantified to understand variations in cardiac glycoside receptor levels during development.
Cross-Sectional (n=18)
Myocardial Na,K-ATPase concentration decreases rapidly within the first 6 months of life, which may explain age-dependent changes in cardiac glycoside sensitivity and toxicity in young children.
May inform age-adjusted cardiac glycoside dosing in neonates; leaves open causal links to toxicity.
Myocardial Na,K-ATPase concentration was quantified in 18 0-8-year-old human subjects by vanadate-facilitated 3H-ouabain binding to intact samples of the left ventricle of the heart obtained at autopsy. Within the first 6 months of life, the Na,K-ATPase concentration showed a rapid decrease. The mean value in the age range from birth to 6 months was 1.6 times the mean value obtained in the age range 6 months to 8 years. The mean values +/- SEM were 1,076 +/- 57 (n = 10) and 671 +/- 28 (n = 8) (p less than 0.001) pmol/g wet weight, respectively. The highest value [1,433 +/- 56 pmol/g wet weight (n = 5)] was found in a 3-month-old child and the lowest value [545 +/- 22 pmol/g wet weight (n = 5)] in an 8-year-old. Evaluation of 3H-ouabain-binding kinetics showed no age-dependent variations. The total amount of Na,K-ATPase found in the heart was approximately 30 and 80 nmol within the first 3 years of life and at 8 years, respectively. The age-dependent change in myocardial Na,K-ATPase concentration can be ascribed to variation in the ratio between the amount of Na,K-ATPase and muscle mass during development. Since myocardial Na,K-ATPase is the receptor for cardiac glycosides, the present results may in part explain the clinical observation that cardiac glycoside sensitivity and toxicity change in young age.
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Kjeldsen et al. (1990) reported a cross-sectional. Age 0 to 6 months vs. Age 6 months to 8 years was evaluated on Myocardial Na,K-ATPase concentration (pmol/g wet weight) (p=<0.001). Myocardial Na,K-ATPase concentration was significantly higher in children aged 0 to 6 months compared to those aged 6 months to 8 years (1,076 vs 671 pmol/g wet weight; p<0.001).
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